https://hemonc.org/w/api.php?action=feedcontributions&user=Wayneliang&feedformat=atomHemOnc.org - A Hematology Oncology Wiki - User contributions [en]2024-03-29T05:39:58ZUser contributionsMediaWiki 1.35.14https://hemonc.org/w/index.php?title=User_talk:Wayneliang&diff=66589User talk:Wayneliang2023-02-27T22:37:10Z<p>Wayneliang: add signature</p>
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<div>This is a sandbox<br />
<br />
[[User:Wayneliang|Wayne H Liang, MD MS]] ([[User talk:Wayneliang|talk]]) 22:36, 27 February 2023 (UTC)</div>Waynelianghttps://hemonc.org/w/index.php?title=User_talk:Wayneliang&diff=66212User talk:Wayneliang2023-02-13T22:39:16Z<p>Wayneliang: sandbox</p>
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<div>This is a sandbox</div>Waynelianghttps://hemonc.org/w/index.php?title=Classical_Hodgkin_lymphoma,_pediatric&diff=56355Classical Hodgkin lymphoma, pediatric2022-05-18T17:04:58Z<p>Wayneliang: /* ABVE-PC (COG AHOD1331) */</p>
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<div>{{#lst:Section editor transclusions|peds}}<br />
<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big><br><br><br />
''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Hodgkin_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Hodgkin lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br><br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=4}}<br />
=Guidelines=<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)]<br />
=Upfront Therapy, High Risk=<br />
==COG AHOD1331==<br />
===Standard Arm (ABVE-PC COG AHOD1331)===<br />
====Cycles 1 to 5====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once on days 1 & 2<br />
**Concentration not to exceed 2 mg/mL<br />
**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1 & 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3<br />
**Rate should not exceed 300 mg/m<sup>2</sup><br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO BID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 & 2<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV daily beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC > 1000/μL<br />
**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6<br />
Response evaluation after cycle 2<br />
'''21 day cycle'''<br />
===Experimental Arm (Bv-AVEPC)===<br />
====Cycles 1 to 5====<br />
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg (maximum dose of 180 mg) IV over 30 minutes once on day 1<br />
**[[Brentuximab vedotin (Adcetris)]] should be given prior to other chemotherapy<br />
**Do NOT use In Line Filters<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once on days 1 & 2<br />
**Concentration not to exceed 2 mg/mL<br />
**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 8<br />
**<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3<br />
**Rate should not exceed 300 mg/m<sup>2</sup><br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO BID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 & 2<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV daily beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC > 1000/μL<br />
**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6<br />
Response evaluation after cycle 2<br />
'''21 day cycle'''<br />
===References===<br />
# '''COG AHOD1331:''' Mailhot Vega RB, Castellino SM, Pei Q, Parsons S, Roberts KB, Hodgson D, Charpentier AM, Fitzgerald TJ, Kessel SK, Keller FG, Kelly K, and Hoppe BS. Evaluating Disparities in Proton Radiation Therapy Use in AHOD1331, A Contemporary Children's Oncology Group Trial for Advanced-Stage Hodgkin Lymphoma. Int J Part Ther. 2021 Oct 28;8(3):55-57. [https://doi.org/10.14338/ijpt-21-00012.1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8768892/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35127976/ PubMed] NCT02166463<br />
=Upfront Therapy, Intermediate Risk=<br />
==ABVE-PC (COG AHOD0031)==<br />
===Rapid Early Responders (Standard Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====Involved Field Radiation Therapy====<br />
===Rapid Early Responders (Reduced Therapy Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====No Further Treatment====<br />
===Slow Early Responders (Standard Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
===Slow Early Responders (Augmented Therapy Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Therapy====<br />
====DECA Therapy x 2 Cycles====<br />
=====Chemotherapy=====<br />
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2<br />
**[[Dexamethasone (Decadron)]] to be given prior to [[Etoposide (Vepesid)]]/[[Cytarabine (Ara-C)]]<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 2<br />
**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL<br />
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours on days 1, 2<br />
**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL<br />
*[[Cisplatin (Platinol)]] 90 mg/m<sup>2</sup> IV over 6 hours once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
====References====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
=Upfront Therapy, Low Risk=<br />
==OEPA (GPOD-HD-2002) {{#subobject:0e614f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)<br />
===Regimen {{#subobject:25c262|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.''<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Treatment group 2: [[#COPDAC|COPDAC]] x 2<br />
*Treatment group 3: [[#COPDAC|COPDAC]] x 4<br />
===References===<br />
# '''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT0041683<br />
= Radiation therapy {{#subobject:b169ea|Regimen=1}}=<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy<br />
===Regimen variant #2, 21 Gy of IFRT {{#subobject:dfa48c|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2002.12.007 Nachman et al. 2002 (CCG 5942)]<br />
|1995-1998<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
|1997-2001<br />
| style="background-color:#91cf61" |Phase 2<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
|2002-2009<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS48<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old.''<br />
====Preceding treatment====<br />
*CCG 5942: [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification<br />
*POG P9425: [[#ABVE-PC|ABVE-PC]] x 3 to 5<br />
*COG AHOD0031 RERs: [[#ABVE-PC|ABVE-PC]] x 4<br />
*COG AHOD0031 SERs: [[#ABVE-PC|ABVE-PC]] x 4 versus [[#ABVE-PC|ABVE-PC]] x 2, then DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2<br />
====Radiotherapy====<br />
*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.5 to 1.75 Gy per fraction<br />
====References====<br />
# '''CCG 5942:''' Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12228196 PubMed] NCT00592111<br />
## '''Update:''' Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136 PubMed]<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
[[Category:Hodgkin lymphoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Aggressive lymphomas]]<br />
[[Category:Pediatric hematologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Classical_Hodgkin_lymphoma,_pediatric&diff=56354Classical Hodgkin lymphoma, pediatric2022-05-18T17:01:19Z<p>Wayneliang: /* References */ made radiation reference to sub-heading 2</p>
<hr />
<div>{{#lst:Section editor transclusions|peds}}<br />
<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big><br><br><br />
''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Hodgkin_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Hodgkin lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br><br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=4}}<br />
=Guidelines=<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)]<br />
=Upfront Therapy, High Risk=<br />
==ABVE-PC (COG AHOD1331)==<br />
===Standard Arm (ABVE-PC)===<br />
====Cycles 1 to 5====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once on days 1 & 2<br />
**Concentration not to exceed 2 mg/mL<br />
**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1 & 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3<br />
**Rate should not exceed 300 mg/m<sup>2</sup><br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO BID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 & 2<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV daily beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC > 1000/μL<br />
**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6<br />
Response evaluation after cycle 2<br />
'''21 day cycle'''<br />
===Experimental Arm (Bv-AVEPC)===<br />
====Cycles 1 to 5====<br />
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg (maximum dose of 180 mg) IV over 30 minutes once on day 1<br />
**[[Brentuximab vedotin (Adcetris)]] should be given prior to other chemotherapy<br />
**Do NOT use In Line Filters<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once on days 1 & 2<br />
**Concentration not to exceed 2 mg/mL<br />
**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 8<br />
**<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3<br />
**Rate should not exceed 300 mg/m<sup>2</sup><br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO BID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 & 2<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV daily beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC > 1000/μL<br />
**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6<br />
Response evaluation after cycle 2<br />
'''21 day cycle'''<br />
===References===<br />
# '''COG AHOD1331:''' Mailhot Vega RB, Castellino SM, Pei Q, Parsons S, Roberts KB, Hodgson D, Charpentier AM, Fitzgerald TJ, Kessel SK, Keller FG, Kelly K, and Hoppe BS. Evaluating Disparities in Proton Radiation Therapy Use in AHOD1331, A Contemporary Children's Oncology Group Trial for Advanced-Stage Hodgkin Lymphoma. Int J Part Ther. 2021 Oct 28;8(3):55-57. [https://doi.org/10.14338/ijpt-21-00012.1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8768892/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35127976/ PubMed] NCT02166463<br />
=Upfront Therapy, Intermediate Risk=<br />
==ABVE-PC (COG AHOD0031)==<br />
===Rapid Early Responders (Standard Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====Involved Field Radiation Therapy====<br />
===Rapid Early Responders (Reduced Therapy Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====No Further Treatment====<br />
===Slow Early Responders (Standard Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
===Slow Early Responders (Augmented Therapy Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Therapy====<br />
====DECA Therapy x 2 Cycles====<br />
=====Chemotherapy=====<br />
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2<br />
**[[Dexamethasone (Decadron)]] to be given prior to [[Etoposide (Vepesid)]]/[[Cytarabine (Ara-C)]]<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 2<br />
**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL<br />
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours on days 1, 2<br />
**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL<br />
*[[Cisplatin (Platinol)]] 90 mg/m<sup>2</sup> IV over 6 hours once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
====References====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
=Upfront Therapy, Low Risk=<br />
==OEPA (GPOD-HD-2002) {{#subobject:0e614f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)<br />
===Regimen {{#subobject:25c262|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.''<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Treatment group 2: [[#COPDAC|COPDAC]] x 2<br />
*Treatment group 3: [[#COPDAC|COPDAC]] x 4<br />
===References===<br />
# '''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT0041683<br />
= Radiation therapy {{#subobject:b169ea|Regimen=1}}=<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy<br />
===Regimen variant #2, 21 Gy of IFRT {{#subobject:dfa48c|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2002.12.007 Nachman et al. 2002 (CCG 5942)]<br />
|1995-1998<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
|1997-2001<br />
| style="background-color:#91cf61" |Phase 2<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
|2002-2009<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS48<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old.''<br />
====Preceding treatment====<br />
*CCG 5942: [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification<br />
*POG P9425: [[#ABVE-PC|ABVE-PC]] x 3 to 5<br />
*COG AHOD0031 RERs: [[#ABVE-PC|ABVE-PC]] x 4<br />
*COG AHOD0031 SERs: [[#ABVE-PC|ABVE-PC]] x 4 versus [[#ABVE-PC|ABVE-PC]] x 2, then DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2<br />
====Radiotherapy====<br />
*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.5 to 1.75 Gy per fraction<br />
====References====<br />
# '''CCG 5942:''' Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12228196 PubMed] NCT00592111<br />
## '''Update:''' Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136 PubMed]<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
[[Category:Hodgkin lymphoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Aggressive lymphomas]]<br />
[[Category:Pediatric hematologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Classical_Hodgkin_lymphoma,_pediatric&diff=56353Classical Hodgkin lymphoma, pediatric2022-05-18T17:00:16Z<p>Wayneliang: Moved ABVE-PC (POG P9425) to historical</p>
<hr />
<div>{{#lst:Section editor transclusions|peds}}<br />
<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big><br><br><br />
''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Hodgkin_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Hodgkin lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br><br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=4}}<br />
=Guidelines=<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)]<br />
=Upfront Therapy, High Risk=<br />
==ABVE-PC (COG AHOD1331)==<br />
===Standard Arm (ABVE-PC)===<br />
====Cycles 1 to 5====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once on days 1 & 2<br />
**Concentration not to exceed 2 mg/mL<br />
**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1 & 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3<br />
**Rate should not exceed 300 mg/m<sup>2</sup><br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO BID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 & 2<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV daily beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC > 1000/μL<br />
**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6<br />
Response evaluation after cycle 2<br />
'''21 day cycle'''<br />
===Experimental Arm (Bv-AVEPC)===<br />
====Cycles 1 to 5====<br />
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg (maximum dose of 180 mg) IV over 30 minutes once on day 1<br />
**[[Brentuximab vedotin (Adcetris)]] should be given prior to other chemotherapy<br />
**Do NOT use In Line Filters<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once on days 1 & 2<br />
**Concentration not to exceed 2 mg/mL<br />
**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 8<br />
**<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3<br />
**Rate should not exceed 300 mg/m<sup>2</sup><br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO BID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 & 2<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV daily beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC > 1000/μL<br />
**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6<br />
Response evaluation after cycle 2<br />
'''21 day cycle'''<br />
===References===<br />
# '''COG AHOD1331:''' Mailhot Vega RB, Castellino SM, Pei Q, Parsons S, Roberts KB, Hodgson D, Charpentier AM, Fitzgerald TJ, Kessel SK, Keller FG, Kelly K, and Hoppe BS. Evaluating Disparities in Proton Radiation Therapy Use in AHOD1331, A Contemporary Children's Oncology Group Trial for Advanced-Stage Hodgkin Lymphoma. Int J Part Ther. 2021 Oct 28;8(3):55-57. [https://doi.org/10.14338/ijpt-21-00012.1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8768892/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35127976/ PubMed] NCT02166463<br />
=Upfront Therapy, Intermediate Risk=<br />
==ABVE-PC (COG AHOD0031)==<br />
===Rapid Early Responders (Standard Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====Involved Field Radiation Therapy====<br />
===Rapid Early Responders (Reduced Therapy Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====No Further Treatment====<br />
===Slow Early Responders (Standard Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
===Slow Early Responders (Augmented Therapy Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Therapy====<br />
====DECA Therapy x 2 Cycles====<br />
=====Chemotherapy=====<br />
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2<br />
**[[Dexamethasone (Decadron)]] to be given prior to [[Etoposide (Vepesid)]]/[[Cytarabine (Ara-C)]]<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 2<br />
**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL<br />
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours on days 1, 2<br />
**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL<br />
*[[Cisplatin (Platinol)]] 90 mg/m<sup>2</sup> IV over 6 hours once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
====References====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
=Upfront Therapy, Low Risk=<br />
==OEPA (GPOD-HD-2002) {{#subobject:0e614f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)<br />
===Regimen {{#subobject:25c262|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.''<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Treatment group 2: [[#COPDAC|COPDAC]] x 2<br />
*Treatment group 3: [[#COPDAC|COPDAC]] x 4<br />
===References===<br />
# '''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT0041683<br />
= Radiation therapy {{#subobject:b169ea|Regimen=1}}=<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy<br />
===Regimen variant #2, 21 Gy of IFRT {{#subobject:dfa48c|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2002.12.007 Nachman et al. 2002 (CCG 5942)]<br />
|1995-1998<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
|1997-2001<br />
| style="background-color:#91cf61" |Phase 2<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
|2002-2009<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS48<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old.''<br />
====Preceding treatment====<br />
*CCG 5942: [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification<br />
*POG P9425: [[#ABVE-PC|ABVE-PC]] x 3 to 5<br />
*COG AHOD0031 RERs: [[#ABVE-PC|ABVE-PC]] x 4<br />
*COG AHOD0031 SERs: [[#ABVE-PC|ABVE-PC]] x 4 versus [[#ABVE-PC|ABVE-PC]] x 2, then DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2<br />
====Radiotherapy====<br />
*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.5 to 1.75 Gy per fraction<br />
===References===<br />
# '''CCG 5942:''' Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12228196 PubMed] NCT00592111<br />
## '''Update:''' Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136 PubMed]<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
[[Category:Hodgkin lymphoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Aggressive lymphomas]]<br />
[[Category:Pediatric hematologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Classical_Hodgkin_lymphoma_-_historical&diff=56352Classical Hodgkin lymphoma - historical2022-05-18T17:00:10Z<p>Wayneliang: Moved ABVE-PC (POG P9425) to historical</p>
<hr />
<div>The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Hodgkin_lymphoma|main Hodgkin lymphoma page]] for current regimens.<br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=3}}<br />
=Untreated=<br />
==ABVDm {{#subobject:3065be|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVDm: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine, '''<u>m</u>'''ethylprednisolone<br />
===Regimen {{#subobject:c39ab4|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[http://www.bloodjournal.org/content/103/1/58.long Le Maignan et al. 2003 (H90-NM)]<br />
|1990-1996<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[#EBVMm_99|EBVMm]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Dacarbazine (DTIC)]]<br />
*[[Methylprednisolone (Solumedrol)]]<br />
===References===<br />
# '''H90-NM:''' Le Maignan C, Desablens B, Delwail V, Dib M, Berthou C, Vigier M, Ghandour C, Atmani S, Casassus P, Maisonneuve H, Le Mevel A, Traulle C, Bernard M, Briere J, Colonna P, Andrieu JM. Three cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) or epirubicin, bleomycin, vinblastine, and methotrexate (EBVM) plus extended field radiation therapy in early and intermediate Hodgkin disease: 10-year results of a randomized trial. Blood. 2004 Jan 1;103(1):58-66. Epub 2003 Aug 7. [http://www.bloodjournal.org/content/103/1/58.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/12907440 PubMed] <br />
<br />
<br />
==ABVE-PC (POG P9425) {{#subobject:c24d93|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
===Regimen variant #2, 3 cycles with response adaptation {{#subobject:14cd95|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}''This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 3 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (5 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #4, 5 cycles {{#subobject:7e95ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}''This regimen is intended for pediatric patients, younger than 22 years old, who are slow early responders. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 3, with slow early response<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 5 cycles, including the first 3 cycles'''<br />
====Subsequent treatment====<br />
*[[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===References===<br />
#'''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
==BCVPP {{#subobject:75779b|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
BCVPP: '''<u>B</u>'''CNU (Carmustine), '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:ab3db2|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142%28197811%2942%3A5%3C2101%3A%3AAID-CNCR2820420504%3E3.0.CO%3B2-M Durant et al. 1978]<br />
|1971-1975<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[http://annals.org/aim/article-abstract/698988/bcvpp-chemotherapy-advanced-hodgkin-s-disease-evidence-greater-duration-complete Bakemeier et al. 1984]<br />
|1972-1976<br />
|style="background-color:#1a9851"|Phase 3 (E-esc)<br />
|[[Hodgkin_lymphoma#MOPP|MOPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<sup>1</sup><br />
|-<br />
|}<br />
''<sup>1</sup>For patients achieving CR, this regimen seemed to have comparatively superior survival.''<br />
====Chemotherapy====<br />
*[[Carmustine (BCNU)]]<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Durant JR, Gams RA, Velez-Garcia E, Bartolucci A, Wirtschafter D, Dorfman R. BCNU, velban, cyclophosphamide, procarbazine, and prednisone (BVCPP) in advanced Hodgkin's disease. Cancer. 1978 Nov;42(5):2101-10. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142%28197811%2942%3A5%3C2101%3A%3AAID-CNCR2820420504%3E3.0.CO%3B2-M link to original article] [https://pubmed.ncbi.nlm.nih.gov/719600 PubMed]<br />
# Bakemeier RF, Anderson JR, Costello W, Rosner G, Horton J, Glick JH, Hines JD, Berard CW, DeVita VT Jr; [[Study_Groups#ECOG|ECOG]]. BCVPP chemotherapy for advanced Hodgkin's disease: evidence for greater duration of complete remission, greater survival, and less toxicity than with a MOPP regimen: results of the Eastern Cooperative Oncology Group study. Ann Intern Med. 1984 Oct;101(4):447-56. [http://annals.org/aim/article-abstract/698988/bcvpp-chemotherapy-advanced-hodgkin-s-disease-evidence-greater-duration-complete link to original article] [https://pubmed.ncbi.nlm.nih.gov/6089632 PubMed]<br />
==ChlVPP/PABIOE {{#subobject:8ee324|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ChlVPP/PABIOE: '''<u>Chl</u>'''orambucil, '''<u>V</u>'''inblastine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>P</u>'''rednisolone, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide<br />
===Protocol {{#subobject:48feb0|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363648/ Hancock et al. 2001]<br />
|1992-1996<br />
| style="background-color:#1a9851" |Randomized (C)<br />
|[[#PABIOE_99|PABIOE]]<br />
| style="background-color:#1a9850" |Superior OS<br />
|-<br />
|}<br />
====Chemotherapy, ChlVPP portion====<br />
*[[Chlorambucil (Leukeran)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisolone (Millipred)]]<br />
====Chemotherapy, PABIOE portion====<br />
*[[Prednisolone (Millipred)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Etoposide (Vepesid)]] <br />
===References===<br />
# Hancock BW, Gregory WM, Cullen MH, Hudson GV, Burton A, Selby P, Maclennan KA, Jack A, Bessell EM, Smith P, Linch DC; British National Lymphoma Investigation; Central Lymphoma Group. ChlVPP alternating with PABlOE is superior to PABlOE alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation/Central Lymphoma Group randomized controlled trial. Br J Cancer. 2001 May 18;84(10):1293-300. [https://www.nature.com/articles/6691778 link to orginal article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363648/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/11355937 PubMed]<br />
# '''UKLG LY09:''' Johnson PW, Radford JA, Cullen MH, Sydes MR, Walewski J, Jack AS, MacLennan KA, Stenning SP, Clawson S, Smith P, Ryder D, Hancock BW; United Kingdom Lymphoma Group. Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol. 2005 Dec 20;23(36):9208-18. Epub 2005 Nov 28. [https://doi.org/10.1200/JCO.2005.03.2151 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/16314615 PubMed] ISRCTN97144519<br />
## '''Subgroup analysis:''' Johnson PW, Sydes MR, Hancock BW, Cullen M, Radford JA, Stenning SP. Consolidation radiotherapy in patients with advanced Hodgkin's lymphoma: survival data from the UKLG LY09 randomized controlled trial (ISRCTN97144519). J Clin Oncol. 2010 Jul 10;28(20):3352-9. Epub 2010 May 24. [https://doi.org/10.1200/JCO.2009.26.0323 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20498402 PubMed]<br />
==COMP {{#subobject:8ee324|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
COMP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:48feb0|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://cancerres.aacrjournals.org/content/27/7/1258.long Moxley et al. 1967]<br />
| style="background-color:#ffffbe" |Pilot<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Methotrexate (MTX)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Moxley JH 3rd, De Vita VT, Brace K, Frei E 3rd. Intensive combination chemotherapy and X-irradiation in Hodgkin's disease. Cancer Res. 1967 Jul;27(7):1258-63. [http://cancerres.aacrjournals.org/content/27/7/1258.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/4952914 PubMed]<br />
==COPP (CCNU) {{#subobject:86879b|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
COPP: '''<u>C</u>'''CNU (Lomustine), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:cf3db2|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|rowspan=3|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract Cooper et al. 1980]<br />
|rowspan=3|1972-1975<br />
|rowspan=3 style="background-color:#1a9851"|Phase 3 (E-switch-ic)<br />
|1. [[#CVPP|CVPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|2. [[Hodgkin_lymphoma#MOPP|MOPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|3. [[#MVPP|MVPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Lomustine (CCNU)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/7397630 PubMed]<br />
==COPP/ABVD {{#subobject:92a2c8|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
COPP/ABVD: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine<br />
<br>C-MOPP/ABVD: '''<u>C</u>'''yclophospha'''<u>M</u>'''ide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine<br />
===Protocol variant #1, 4 cycles {{#subobject:771e81|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2002.20.2.476 Sieber et al. 2002 (GHSG HD5)]<br />
|1988-1993<br />
|style="background-color:#1a9851"|Phase 3 (C)<br />
|[[#COPP.2FABV.2FIMEP_99|COPP/ABV/IMEP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|[https://doi.org/10.1093/annonc/mdh046 Sieber et al. 2004 (GHSG HD6)]<br />
|1988-1993<br />
|style="background-color:#1a9851"|Phase 3 (C)<br />
|[[#COPP.2FABV.2FIMEP_99|COPP/ABV/IMEP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|[https://doi.org/10.1200/JCO.2003.03.023 Engert et al. 2003 (GHSG HD8)]<br />
|1993-1998<br />
|style="background-color:#91cf61"|Non-randomized portion of RCT<br />
|style="background-color:#d3d3d3"|<br />
|style="background-color:#d3d3d3"|<br />
|-<br />
|}<br />
====Chemotherapy, COPP portion====<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
'''28-day cycle for 2 total cycles of COPP, alternating with 2 total cycles of ABVD'''<br />
====Chemotherapy, ABVD portion====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Dacarbazine (DTIC)]]<br />
'''28-day cycle for 2 total cycles of ABVD, alternating with 2 total cycles of COPP'''<br />
====Subsequent treatment====<br />
*GHSG HD5 & HD6: [[Hodgkin_lymphoma#Radiation_therapy_2|EFRT]]<br />
*GHSG HD8: [[Hodgkin_lymphoma#Radiation_therapy_2|EFRT]] versus [[Hodgkin_lymphoma#Radiation_therapy_2|IFRT]]<br />
===Protocol variant #2, 6 cycles {{#subobject:6d7f98|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1093/oxfordjournals.annonc.a059357 Diehl et al. 1995 (GHSG HD3)]<br />
|style="background-color:#91cf61"|Non-randomized portion of RCT<br />
|-<br />
|}<br />
====Chemotherapy, COPP portion====<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
'''28-day cycle for 3 total cycles of COPP, alternating with 3 total cycles of ABVD'''<br />
====Chemotherapy, ABVD portion====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Dacarbazine (DTIC)]]<br />
'''28-day cycle for 3 total cycles of ABVD, alternating with 3 total cycles of COPP'''<br />
====Subsequent treatment====<br />
*COPP/ABVD x 1 (8 cycles total) versus IFRT<br />
===Protocol variant #3, 10 cycles {{#subobject:faa63|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://jjco.oxfordjournals.org/content/30/3/146.long Takenaka et al. 2000 (JCOG 8905)]<br />
|1989-1993<br />
|style="background-color:#91cf61"|Phase 2<br />
|style="background-color:#d3d3d3"|<br />
|style="background-color:#d3d3d3"|<br />
|-<br />
|[https://doi.org/10.1200/jco.1998.16.12.3810 Diehl et al. 1998 (GHSG HD9)]<br />
|1993-1998<br />
|style="background-color:#1a9851"|Phase 3 (C)<br />
|1. [[Hodgkin_lymphoma#BEACOPP_2|BEACOPP]]<br> 2. [[Hodgkin_lymphoma#eBEACOPP_2|eBEACOPP]]<br />
|style="background-color:#fc8d59"|Seems to have inferior OS<br />
|-<br />
|[https://doi.org/10.1093/annonc/mdi023 Ballova et al. 2005 (GHSG HD9elderly)]<br />
|1993-1998<br />
|style="background-color:#1a9851"|Phase 3 (C)<br />
|[[Hodgkin_lymphoma#BEACOPP_2|BEACOPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy, COPP portion====<br />
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8<br />
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> (maximum dose of 150 mg) PO once per day on days 1 to 14<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 3, 8 to 10<br />
'''28-day cycle for 5 total cycles of COPP, alternating with 5 total cycles of ABVD'''<br />
====Chemotherapy, ABVD portion====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
*[[Bleomycin (Blenoxane)]] 9 mg/m<sup>2</sup> (maximum dose of 15 mg) IV once per day on days 1 & 15 <br />
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> (maximum dose of 10 mg) IV once per day on days 1 & 15<br />
*[[Dacarbazine (DTIC)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 5 total cycles of ABVD, alternating with 5 total cycles of COPP'''<br />
====Subsequent treatment====<br />
*Some studies: [[Hodgkin_lymphoma#Radiation_therapy_2|IFRT]] x 30 Gy after completion of chemotherapy was given to patients with bulky (at least 10 cm maximum diameter) disease<br />
====Dose modifications====<br />
*Treatment was postponed for at least 1 week or until recovery if:<br />
**Pretreatment ANC was less than 1500/uL<br />
**Platelet count was less than 100 x 10<sup>9</sup>/L<br />
**AST/S-GOT was greater than 100 IU/L<br />
**Total bilirubin was greater than 2<br />
*Vincristine and vinblastine were temporarily discontinued if patients had grade 2 or greater neurotoxicity (e.g. motor weakness, paresthesia, constipation)<br />
*Doxorubicin was discontinued if cardiac LV ejection fraction was less than 50%<br />
*Bleomycin was stopped if the PaO2 was less than 70 mmHg or if it decreased more than 10 mmHg from the previous measurement<br />
*Note: Dacarbazine 250 mg/m<sup>2</sup> was used at this dose reduction based on experiences in a pilot study in which there was severe emesis with 375 mg/m<sup>2</sup>.<br />
===References===<br />
# '''GHSG HD3:''' Diehl V, Loeffler M, Pfreundschuh M, Ruehl U, Hasenclever D, Nisters-Backes H, Sieber M, Smith K, Tesch H, Geilen W, Adler M, Bartels H, Brandenburg U, Diezler P, Doelken G, Enzian J, Fuchs R, Gassmann W, Gerhartz H, Hagenaukamp U, Hecht T, Hiller E, Hinkelbein H, Lathan B, Kirchner H, Kuehn G, Kuerten H, Loos U, Makoski B, Oertel W, Petsch S, Pfab R, Pflueger H, Planker M, Rohioff R, Sack H, Samandari S, Sauer R, Schalk K, Schmitz G, Schoppe W, Schwieder G, Szepesi S, Teichmann J, Wilhelmy W, Worst P, Fischer R, Georgii A, Huebner E, Schwarze EW; German Hodgkin's Study Group. Further chemotherapy versus low-dose involved-field radiotherapy as consolidation of complete remission after six cycles of alternating chemotherapy in patients with advance Hodgkin's disease. Ann Oncol. 1995 Nov;6(9):901-10. [https://doi.org/10.1093/oxfordjournals.annonc.a059357 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8624293 PubMed]<br />
# '''GHSG HD9:''' Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Rueffer JU, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duehmke E, Georgii A, Loeffler M. BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 1998 Dec;16(12):3810-21. [https://doi.org/10.1200/jco.1998.16.12.3810 link to original article]'''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/9850026 PubMed]<br />
## '''Update:''' Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dörken B, Müller-Hermelink HK, Dühmke E, Loeffler M; German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12;348(24):2386-95. [https://www.nejm.org/doi/full/10.1056/NEJMoa022473 link to original article]'''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/12802024 PubMed]<br />
## '''Update:''' Engert A, Diehl V, Franklin J, Lohri A, Dörken B, Ludwig WD, Koch P, Hänel M, Pfreundschuh M, Wilhelm M, Trümper L, Aulitzky WE, Bentz M, Rummel M, Sezer O, Müller-Hermelink HK, Hasenclever D, Löffler M. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009 Sep 20;27(27):4548-54. [https://doi.org/10.1200/jco.2008.19.8820 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19704068 PubMed]<br />
## '''Update:''' von Tresckow B, Kreissl S, Dipl-Math HG, Bröckelmann PJ, Pabst T, Fridrik M, Rummel M, Jung W, Thiemer J, Sasse S, Bürkle C, Baues C, Diehl V, Engert A, Borchmann P; German Hodgkin Study Group. Intensive treatment strategies in advanced-stage Hodgkin's lymphoma (HD9 and HD12): analysis of long-term survival in two randomised trials. Lancet Haematol. 2018 Oct 01;5(10):e462-73. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30140-6/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/30290903 PubMed]<br />
# '''JCOG 8905:''' Takenaka T, Mikuni C, Miura A, Sasaki T, Suzuki H, Hotta T, Hirano M, Fukuhara S, Sugiyama H, Nasu K, Dohi H, Kozuru M, Tomonaga M, Tajima K, Niimi M, Fukuda H, Mukai K, Shimoyama M; Lymphoma Study Group of the Japan Clinical Oncology Group. Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). Jpn J Clin Oncol. 2000 Mar;30(3):146-52. [https://jjco.oxfordjournals.org/content/30/3/146.long link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/10798542 PubMed]<br />
# '''GHSG HD5:''' Sieber M, Tesch H, Pfistner B, Rueffer U, Lathan B, Brosteanu O, Paulus U, Koch T, Pfreundschuh M, Loeffler M, Engert A, Josting A, Wolf J, Hasenclever D, Franklin J, Duehmke E, Georgii A, Schalk KP, Kirchner H, Doelken G, Munker R, Koch P, Herrmann R, Greil R, Anselmo AP, Diehl V. Rapidly alternating COPP/ABV/IMEP is not superior to conventional alternating COPP/ABVD in combination with extended-field radiotherapy in intermediate-stage Hodgkin's lymphoma: final results of the German Hodgkin's Lymphoma Study Group Trial HD5. J Clin Oncol. 2002 Jan 15;20(2):476-84. [https://doi.org/10.1200/JCO.2002.20.2.476 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11786577 PubMed]<br />
# '''GHSG HD8:''' Engert A, Schiller P, Josting A, Herrmann R, Koch P, Sieber M, Boissevain F, De Wit M, Mezger J, Duhmke E, Willich N, Muller RP, Schmidt BF, Renner H, Muller-Hermelink HK, Pfistner B, Wolf J, Hasenclever D, Loffler M, Diehl V; German Hodgkin's Lymphoma Study Group. Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2003 Oct 1;21(19):3601-8. Epub 2003 Aug 11. [https://doi.org/10.1200/JCO.2003.03.023 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/12913100 PubMed]<br />
## '''Update:''' Sasse S, Klimm B, Görgen H, Fuchs M, Heyden-Honerkamp A, Lohri A, Koch O, Wilhelm M, Trenn G, Finke J, Müller RP, Diehl V, Eich HT, Borchmann P, Engert A; German Hodgkin Study Group (GHSG). Comparing long-term toxicity and efficacy of combined modality treatment including extended- or involved-field radiotherapy in early-stage Hodgkin's lymphoma. Ann Oncol. 2012 Nov;23(11):2953-9. Epub 2012 Jul 5. [https://doi.org/10.1093/annonc/mds110 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22767583 PubMed]<br />
## '''Update:''' Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, Buerkle C, Borchmann S, Fuchs M, Borchmann P, Diehl V, Engert A. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017 Jun 20;35(18):1999-2007. Epub 2017 Apr 18. [https://doi.org/10.1200/JCO.2016.70.9410 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28418763 PubMed]<br />
# '''GHSG HD6:''' Sieber M, Tesch H, Pfistner B, Rueffer U, Paulus U, Munker R, Hermann R, Doelken G, Koch P, Oertel J, Roller S, Worst P, Bischof H, Glunz A, Greil R, von Kalle K, Schalk KP, Hasenclever D, Brosteanu O, Duehmke E, Georgii A, Engert A, Loeffler M, Diehl V, Mueller RP, Willich N, Fischer R, Hansmann ML, Stein H, Schober T, Koch B; German Hodgkin's Lymphoma Study Group. Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial. Ann Oncol. 2004 Feb;15(2):276-82. [https://doi.org/10.1093/annonc/mdh046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14760122 PubMed]<br />
# '''GHSG HD9elderly:''' Ballova V, Rüffer JU, Haverkamp H, Pfistner B, Müller-Hermelink HK, Dühmke E, Worst P, Wilhelmy M, Naumann R, Hentrich M, Eich HT, Josting A, Löffler M, Diehl V, Engert A. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005 Jan;16(1):124-31. [https://doi.org/10.1093/annonc/mdi023 link to original article]'''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/15598949 PubMed]<br />
==CVPP {{#subobject:be8f99|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
CVPP: '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''inblastine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:e71c98|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|rowspan=3|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract Cooper et al. 1980]<br />
|rowspan=3|1972-1975<br />
|rowspan=3 style="background-color:#1a9851"|Phase 3 (E-switch-ic)<br />
|1. [[#COPP_.28CCNU.29|COPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|2. [[Hodgkin_lymphoma#MOPP|MOPP]]<br />
|style="background-color:#91cf60"|Seems to have superior CR rate<br />
|-<br />
|3. [[#MVPP|MVPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|[https://academic.oup.com/jnci/article-abstract/80/18/1466/943469 Pavlovsky et al. 1988]<br />
|1977-1986<br />
|style="background-color:#1a9851"|Randomized (E-de-esc)<br />
|[[#CVPP_.26_88|CVPP & RT]]<br />
| style="background-color:#d73027" |Inferior FFS<sup>1</sup><br />
|-<br />
|[https://doi.org/10.1200/JCO.1997.15.7.2652 Pavlovsky et al. 1997]<br />
|1986-NR<br />
|style="background-color:#1a9851"|Randomized (C)<br />
|[[#AOPE_99|AOPE]]<br />
|style="background-color:#91cf60"|Seems to have superior CR rate<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1096-911X(199712)29:6%3C544::AID-MPO5%3E3.0.CO;2-K Sackmann-Muriel et al. 1997]<br />
|1987-1994<br />
|style="background-color:#1a9851"|Randomized (C)<br />
|[[#AOPE_99|AOPE]]<br />
|style="background-color:#91cf60"|Seems to have superior EFS<br />
|-<br />
|}<br />
''<sup>1</sup>No advantage was seen for either arm in the favorable prognosis group, whereas this arm had inferior DFS for the unfavorable prognosis group.''<br />
====Chemotherapy====<br />
*[[Lomustine (CCNU)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/7397630 PubMed]<br />
# Pavlovsky S, Maschio M, Santarelli MT, Sackmann Muriel F, Corrado C, Garcia I, Schwartz L, Montero C, Lobo Sanahuja F, Magnasco O, Raha R, Cavagnaro F. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage I-II Hodgkin's disease. J Natl Cancer Inst. 1988 Nov 16;80(18):1466-73. [https://academic.oup.com/jnci/article-abstract/80/18/1466/943469 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3184196 PubMed]<br />
## '''Update:''' Pavlovsky S, Santarelli MT, Sackmann Muriel F, Fernández I, Garcia I, Schwartz L, Montero C, Sanahuja FL, Magnasco H, Costa A, Corrado C, Raha R, Bezares R. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage III-IV A & B Hodgkin's disease. Ann Oncol. 1992 Jul;3(7):533-7. [https://doi.org/10.1093/oxfordjournals.annonc.a058255 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1498073 PubMed]<br />
# Pavlovsky S, Schvartzman E, Lastiri F, Magnasco H, Corrado C, Raslawski E, Cancela ME, Ardaiz MC, Cerutti I, Rosso A, Bruno S, Aranguren PN, Salvarezza A, Donato H, Dibar E, Zirone S; GATLA. Randomized trial of CVPP for three versus six cycles in favorable-prognosis and CVPP versus AOPE plus radiotherapy in intermediate-prognosis untreated Hodgkin's disease. J Clin Oncol. 1997 Jul;15(7):2652-8. [https://doi.org/10.1200/JCO.1997.15.7.2652 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9215837 PubMed]<br />
# Sackmann-Muriel F, Zubizarreta P, Gallo G, Scopinaro M, Alderete D, Alfaro E, Casak S, Chantada G, Felice MS, Quinteros R. Hodgkin disease in children: results of a prospective randomized trial in a single institution in Argentina. Med Pediatr Oncol. 1997 Dec;29(6):544-52. [https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1096-911X(199712)29:6%3C544::AID-MPO5%3E3.0.CO;2-K link to original article] [https://pubmed.ncbi.nlm.nih.gov/9324342 PubMed]<br />
==Doxorubicin & Vinblastine {{#subobject:66828f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:597e32|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2001.19.22.4238 Press et al. 2001 (SWOG S9133)]<br />
|NR-2000<br />
|style="background-color:#1a9851"|Phase 3 (E-esc)<br />
|[[#Radiation_therapy_88|STLI]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 3 cycles'''<br />
====Subsequent treatment====<br />
*STLI<br />
===References===<br />
# '''SWOG S9133:''' Press OW, LeBlanc M, Lichter AS, Grogan TM, Unger JM, Wasserman TH, Gaynor ER, Peterson BA, Miller TP, Fisher RI. Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease. J Clin Oncol. 2001 Nov 15;19(22):4238-44. [https://doi.org/10.1200/JCO.2001.19.22.4238 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/11709567 PubMed] NCT00002495<br />
==LOPP {{#subobject:f2a168|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
LOPP: '''<u>L</u>'''eukeran (Chlorambucil), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:bfcf5a|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.thegreenjournal.com/article/S0167-8140(86)80032-9/pdf Hancock 1986]<br />
|1979-NR<br />
| style="background-color:#1a9851" |Randomized (E-switch-ic)<br />
|[[Hodgkin_lymphoma#MOPP|MOPP]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[https://doi.org/10.1200/JCO.1992.10.8.1252 Hancock et al. 1992]<br />
|1983-1989<br />
| style="background-color:#1a9851" |Randomized (C)<br />
|[[#LOPP.2FEVAP|LOPP/EVAP]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Chlorambucil (Leukeran)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Hancock BW; British National Lymphoma Investigation. Randomised study of MOPP (mustine, Oncovin, procarbazine, prednisone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease. Radiother Oncol. 1986 Nov;7(3):215-21. [https://www.thegreenjournal.com/article/S0167-8140(86)80032-9/pdf link to original article] [https://pubmed.ncbi.nlm.nih.gov/3544084 PubMed]<br />
## '''Update:''' Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Haybittle JL, Bennett MH, MacLennan KA, Jelliffe AM; BNLI. British National Lymphoma Investigation randomised study of MOPP (mustine, Oncovin, procarbazine, prednisolone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease--long term results. Br J Cancer. 1991 Apr;63(4):579-82. [https://doi.org/10.1038/bjc.1991.134 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1972355/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/2021542 PubMed]<br />
# Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Bennett MH, MacLennan KA, Haybittle JL, Anderson L, Linch DC; BNLI. LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial. J Clin Oncol. 1992 Aug;10(8):1252-8. [https://doi.org/10.1200/JCO.1992.10.8.1252 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1634914 PubMed]<br />
==LOPP/EVAP {{#subobject:22b023|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
LOPP/EVAP: '''<u>L</u>'''eukeran (Chlorambucil), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>E</u>'''toposide, '''<u>V</u>'''inblastine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''rednisone<br />
===Protocol {{#subobject:53f4da|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.1992.10.8.1252 Hancock et al. 1992]<br />
|1983-1989<br />
| style="background-color:#1a9851" |Randomized (E-switch-ic)<br />
|[[#LOPP|LOPP]]<br />
| style="background-color:#91cf60" |Seems to have superior OS<br />
|-<br />
|[https://doi.org/10.1093/annonc/5.suppl_2.s117 Hancock et al. 1994]<br />
|1990-1991<br />
| style="background-color:#1a9851" |Randomized (C)<br />
|[[#LOPP-EVA_99|LOPP-EVA]]<br />
| style="background-color:#1a9850" |Superior CR rate<br />
|-<br />
|}<br />
====Chemotherapy, LOPP portion====<br />
*[[Chlorambucil (Leukeran)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
====Chemotherapy, EVAP portion====<br />
*[[Etoposide (Vepesid)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Bennett MH, MacLennan KA, Haybittle JL, Anderson L, Linch DC; BNLI. LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial. J Clin Oncol. 1992 Aug;10(8):1252-8. [https://doi.org/10.1200/JCO.1992.10.8.1252 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1634914 PubMed]<br />
# Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Linch DC, Anderson L, MacLennan KA; BNLI. Hybrid LOPP/EVA is not better than LOPP alternating with EVAP: a prematurely terminated British National Lymphoma Investigation randomized trial. Ann Oncol. 1994;5 Suppl 2:117-20. [https://doi.org/10.1093/annonc/5.suppl_2.s117 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8204511 PubMed]<br />
==Mechlorethamine monotherapy {{#subobject:3674c2|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:2761c1|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://jamanetwork.com/journals/jama/fullarticle/288442 Goodman et al. 1946]<br />
|NR<br />
| style="background-color:#91cf61" |Non-randomized<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://jamanetwork.com/journals/jama/article-abstract/288767 Jacobson et al. 1946]<br />
|1943-1945<br />
| style="background-color:#91cf61" |Non-randomized<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[http://annals.org/aim/article/673669/nitrogen-mustard-therapeutic-agent-hodgkin-s-disease-lymphosarcoma-leukemia Wintrobe et al. 1947]<br />
|NR<br />
| style="background-color:#91cf61" |Non-randomized<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[http://annals.org/aim/article/673986/use-nitrogen-mustard-hodgkin-s-disease-lymphosarcoma Meyer & Overmiller 1949]<br />
|1946-1947<br />
| style="background-color:#91cf61" |Non-randomized<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://jamanetwork.com/journals/jama/article-abstract/337835 Jacobs et al. 1968]<br />
|1960-1963<br />
| style="background-color:#1a9851" |Randomized (C)<br />
|[[#Cyclophosphamide_monotherapy_99|Cyclophosphamide]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
''These references are of major historic interest as they are the first systemic chemotherapy trials in humans. Note that some of these early trials used nitrogen mustards other than mechlorethamine but are grouped here for simplicity.''<br />
====Chemotherapy====<br />
*[[Mechlorethamine (Mustargen)]]<br />
===References===<br />
# Goodman LS, Wintrobe MM, Dameshek W, Goodman MJ, Gilman A, McLennan MT. Nitrogen mustard therapy; use of methyl-bis (beta-chloroethyl) amine hydrochloride and tris (beta-chloroethyl) amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. J Am Med Assoc. 1946 Sep 21;132:126-32. [https://jamanetwork.com/journals/jama/fullarticle/288442 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20997191 PubMed]<br />
# Jacobson LO, Spurr CL, Guzman-Barron ES, Smith T, Lushbaugh C, Dick GF. Nitrogen mustard therapy; studies on the effect of methyl-bis (beta-chloroethyl) amine hydrochloride on neoplastic diseases and allied disorders of the hemopoietic system. J Am Med Assoc. 1946 Oct 5;132:263-71. [https://jamanetwork.com/journals/jama/article-abstract/288767 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20997209 PubMed]<br />
# Wintrobe MM, Huguley CM Jr, McLennan MT, Penna de Carvalho Lima L. Nitrogen mustard as a therapeutic agent for Hodgkin's disease, lymphosarcoma and leukemia. Ann Intern Med. 1947 Oct;27(4):529-40. [http://annals.org/aim/article/673669/nitrogen-mustard-therapeutic-agent-hodgkin-s-disease-lymphosarcoma-leukemia link to original article] [https://pubmed.ncbi.nlm.nih.gov/20268426 PubMed]<br />
# Meyer AH, Overmiller WC. The use of nitrogen mustard in Hodgkin's disease and lymphosarcoma. Ann Intern Med. 1949 Feb;30(2):381-6. [http://annals.org/aim/article/673986/use-nitrogen-mustard-hodgkin-s-disease-lymphosarcoma link to original article] [https://pubmed.ncbi.nlm.nih.gov/18109292 PubMed]<br />
# Jacobs EM, Peters FC, Luce JK, Zippin C, Wood DA. Mechlorethamine HCl and cyclophosphamide in the treatment of Hodgkin's disease and the lymphomas. JAMA. 1968 Feb 5;203(6):392-8. [https://jamanetwork.com/journals/jama/article-abstract/337835 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4865234 PubMed]<br />
==MOPP/ABVD {{#subobject:f28468|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
MOPP/ABVD: '''<u>M</u>'''ustargen (Mechlorethamine), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine<br />
===Protocol {{#subobject:5b28f5|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.nejm.org/doi/full/10.1056/NEJM198204013061303 Santoro et al. 1982]<br />
|1974-1980<br />
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)<br />
|[[Hodgkin_lymphoma#MOPP|MOPP]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|[https://doi.org/10.1200/jco.1994.12.2.279 Somers et al. 1994]<br />
|1981-1986<br />
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)<br />
|[[Hodgkin_lymphoma#MOPP|MOPP]]<br />
| style="background-color:#91cf60" |Seems to have superior FFS<br />
|-<br />
| rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJM199211193272102 Canellos et al. 1992 (CALGB 8251)]<br />
|rowspan=2|1982-NR<br />
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)<br />
|1. [[Hodgkin_lymphoma#ABVD_3|ABVD]]<br />
| style="background-color:#ffffbf" |Seems not superior<sup>1</sup><br />
|-<br />
|2. [[Hodgkin_lymphoma#MOPP|MOPP]]<br />
| style="background-color:#91cf60" |Seems to have superior EFS<sup>1</sup><br />
|-<br />
|[https://doi.org/10.1200/jco.1996.14.5.1421 Viviani et al. 1996]<br />
|1982-1990<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[#MOPP-ABVD_99|MOPP-ABVD]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[https://doi.org/10.1200/jco.1997.15.4.1638 Connor et al. 1997 (NCIC-CTG HD4)]<br />
|1984-1989<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma#MOPP-ABV_3|MOPP-ABV]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[https://doi.org/10.1200/JCO.1998.16.3.897 Hutchinson et al. 1998 (CCG-521)]<br />
|1986-1990<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma#ABVD_3|ABVD]], then [[Hodgkin_lymphoma#Radiation_therapy_2|RT]]<br />
| style="background-color:#fee08b" |Might have inferior EFS<br />
|-<br />
|}<br />
''<sup>1</sup>Reported efficacy for CALGB 8251 is based on the 2009 update.''<br />
====Chemotherapy, MOPP portion====<br />
*[[Mechlorethamine (Mustargen)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
====Chemotherapy, ABVD portion====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Dacarbazine (DTIC)]]<br />
===References===<br />
# Santoro A, Bonadonna G, Bonfante V, Valagussa P. Alternating drug combinations in the treatment of advanced Hodgkin's disease. N Engl J Med. 1982 Apr 1;306(13):770-5. [https://www.nejm.org/doi/full/10.1056/NEJM198204013061303 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6174865 PubMed]<br />
## '''Update:''' Bonadonna G, Valagussa P, Santoro A. Alternating non-cross-resistant combination chemotherapy or MOPP in stage IV Hodgkin's disease: a report of 8-year results. Ann Intern Med. 1986 Jun;104(6):739-46. [http://annals.org/article.aspx?articleid=700485 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2422994 PubMed]<br />
# '''CALGB 8251:''' Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992 Nov 19;327(21):1478-84. [https://www.nejm.org/doi/10.1056/NEJM199211193272102 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1383821 PubMed]<br />
## '''Update:''' Canellos GP, Niedzwiecki D. Long-term follow-up of Hodgkin's disease trial. N Engl J Med. 2002 May 2;346(18):1417-8. [https://www.nejm.org/doi/10.1056/NEJM200205023461821 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11986425 PubMed]<br />
## '''Update:''' Canellos GP, Niedzwiecki D, Johnson JL. Long-term follow-up of survival in Hodgkin's lymphoma. N Engl J Med. 2009 Dec 10;361(24):2390-1. [https://www.nejm.org/doi/10.1056/NEJMc0906731 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20007568 PubMed]<br />
# Somers R, Carde P, Henry-Amar M, Tarayre M, Thomas J, Hagenbeek A, Monconduit M, de Pauw BE, Breed WP, Verdonck L, Burgers JMV, Eghbali H, Zittoun R; [[Study_Groups#EORTC|EORTC]]. A randomized study in stage IIIB and IV Hodgkin's disease comparing eight courses of MOPP versus an alteration of MOPP with ABVD: a European Organisation for Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie controlled clinical trial. J Clin Oncol. 1994 Feb;12(2):279-87. [https://doi.org/10.1200/jco.1994.12.2.279 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7509381 PubMed]<br />
# Viviani S, Bonadonna G, Santoro A, Bonfante V, Zanini M, Devizzi L, Soncini F, Valagussa P. Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin's disease: ten-year results. J Clin Oncol. 1996 May;14(5):1421-30. [https://doi.org/10.1200/jco.1996.14.5.1421 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8622055 PubMed]<br />
# '''NCIC-CTG HD4:''' Connors JM, Klimo P, Adams G, Burns BF, Cooper I, Meyer RM, O'Reilly SE, Pater J, Quirt I, Sadura A, Shustik C, Skillings J, Sutcliffe S, Verma S, Yoshida S, Zee B. Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group. J Clin Oncol. 1997 Apr;15(4):1638-45. Erratum in: J Clin Oncol 1997 Jul;15(7):2762. [https://doi.org/10.1200/jco.1997.15.4.1638 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9193364 PubMed]<br />
# '''CCG-521:''' Hutchinson RJ, Fryer CJ, Davis PC, Nachman J, Krailo MD, O'Brien RT, Collins RD, Whalen T, Reardon D, Trigg ME, Gilchrist GS. MOPP or radiation in addition to ABVD in the treatment of pathologically staged advanced Hodgkin's disease in children: results of the Children's Cancer Group Phase III Trial. J Clin Oncol. 1998 Mar;16(3):897-906. [https://doi.org/10.1200/JCO.1998.16.3.897 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9508171 PubMed]<br />
==MVPP {{#subobject:b01f3a|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
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MVPP: '''<u>M</u>'''echlorethamine, '''<u>V</u>'''inblastine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:312fd8|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|rowspan=3|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract Cooper et al. 1980]<br />
|rowspan=3|1972-1975<br />
|rowspan=3 style="background-color:#1a9851"|Phase 3 (E-switch-ic)<br />
|1. [[#COPP_.28CCNU.29|COPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|2. [[#CVPP|CVPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|3. [[Hodgkin_lymphoma#MOPP|MOPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Mechlorethamine (Mustargen)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/7397630 PubMed]<br />
==NOVP {{#subobject:230457|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
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NOVP: '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>O</u>'''ncovin (Vincristine), '''<u>V</u>'''inblastine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:5bf81f|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://pubmed.ncbi.nlm.nih.gov/2259922 Hagemeister et al. 1990]<br />
|style="background-color:#91cf61"|Phase 2<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Mitoxantrone (Novantrone)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Hagemeister FB, Cabanillas F, Velásquez WS, Meistrich ML, Liang JC, McLaughlin P, Redman JR, Romaguera JE, Rodríguez MA, Swan F Jr, Fuller LM. NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease. Semin Oncol. 1990 Dec;17(6 Suppl 10):34-8. [http://www.seminoncol.org/article/0093-7754(90)90122-J/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/2259922 PubMed]<br />
==SCAB {{#subobject:344883|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
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SCAB: '''<u>S</u>'''treptozocin, '''<u>C</u>'''CNU (Lomustine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin<br />
===Regimen {{#subobject:a68d3b|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19810115)47:2%3C224::AID-CNCR2820470203%3E3.0.CO;2-6/abstract Diggs et al. 1981]<br />
|style="background-color:#91cf61"|Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Streptozocin (Zanosar)]]<br />
*[[Lomustine (CCNU)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
===References===<br />
# Diggs CH, Wiernik PH, Sutherland JC. Treatment of advanced untreated Hodgkin's disease with SCAB--an alternative to MOPP. Cancer. 1981 Jan 15;47(2):224-8. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19810115)47:2%3C224::AID-CNCR2820470203%3E3.0.CO;2-6/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/6161689 PubMed]<br />
## '''Update:''' Wiernik PH, Schiffer CA. Long-term follow-up of advanced Hodgkin's disease patients treated with a combination of streptozotocin, lomustine (CCNU), doxorubicin and bleomycin (SCAB). J Cancer Res Clin Oncol. 1988;114(1):105-7. [https://doi.org/10.1007/bf00390494 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2450876 PubMed]<br />
==Vinblastine monotherapy {{#subobject:b1c2da|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
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|}<br />
===Regimen {{#subobject:48bfd8|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://jamanetwork.com/journals/jama/article-abstract/657749 Stutzman et al. 1966]<br />
|1963-1964<br />
|style="background-color:#1a9851"|Randomized (E-switch-ic)<br />
|[[#Cyclophosphamide_monotherapy_88|Cyclophosphamide]]<br />
| style="background-color:#1a9850" |Superior ORR<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Vinblastine (Velban)]]<br />
===References===<br />
# Stutzman L, Ezdinli EZ, Stutzman MA. Vinblastine sulfate vs cyclophosphamide in the therapy for lymphoma. JAMA. 1966 Jan 17;195(3):173-8. [https://jamanetwork.com/journals/jama/article-abstract/657749 link to original article] [https://pubmed.ncbi.nlm.nih.gov/5322863 PubMed]<br />
==OPPA {{#subobject:6418c0|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
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OPPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)<br />
===Regimen {{#subobject:e17569|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" | Phase II<br />
|-<br />
|}<br />
''This regimen is meant for girls. Patients with early-stage disease only received the OPPA portion, see text for details.''<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Treatment group 2: [[#C-MOPP|COPP]] x 2<br />
*Treatment group 3: [[#C-MOPP|COPP]] x 4<br />
===References===<br />
#'''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
==VAMP (Methotrexate) {{#subobject:4d666a|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
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|}<br />
VAMP: '''<u>V</u>'''inblastine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethrotrexate, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:6f694d|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526806/ Metzger et al. 2012 (HOD99)]<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''To be completed? This is to be distinguished from the VAMP protocols used in AML and multiple myeloma.''<br />
====Chemotherapy====<br />
*[[Vinblastine (Velban)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Methotrexate (MTX)]]<br />
*[[Prednisone (Sterapred)]]<br />
'''4 cycles'''<br />
====Subsequent treatment====<br />
*Early responders: [[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]] versus [[#Radiation_therapy_2|RT]]<br />
===References===<br />
#'''HOD99:''' Metzger ML, Weinstein HJ, Hudson MM, Billett AL, Larsen EC, Friedmann A, Howard SC, Donaldson SS, Krasin MJ, Kun LE, Marcus KJ, Yock TI, Tarbell N, Billups CA, Wu J, Link MP. Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma. JAMA. 2012 Jun 27;307(24):2609-16. [https://jamanetwork.com/journals/jama/fullarticle/1199151 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526806/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22735430 PubMed]<br />
==ABVE {{#subobject:c24h71|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
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ABVE: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide<br />
===Regimen {{#subobject:7fa7ya|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3468662/ Tebbi et al. 2012 (POG P9426)]<br />
|1996-2001<br />
| style="background-color:#91cf61" |Non-randomized (see note)<br />
|-<br />
|}<br />
''Note: this trial had a randomization to receive or not receive dexrazoxane. Labeled here as non-randomized because this drug does not have antineoplastic properties.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV once per day on days 1 & 15<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 15<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5<br />
====Supportive medications====<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 6 to 14, then once per day on days 16 until ANC greater than 1000/uL<br />
'''28-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*CR: [[#Radiation_therapy_2|IFRT consolidation]]<br />
*Other than CR: [[#ABVE|ABVE]] x 2, then [[#Radiation_therapy_2|IFRT consolidation]]<br />
===References===<br />
#'''POG P9426:''' Tebbi CK, Mendenhall NP, London WB, Williams JL, Hutchison RE, Fitzgerald TJ, de Alarcón PA, Schwartz C, Chauvenet A. Response-dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2012 Dec 15;59(7):1259-65. Epub 2012 Aug 21. [https://doi.org/10.1002/pbc.24279 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3468662/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/22911615/ PubMed] NCT00002827<br />
==MOPP {{#subobject:bcde0|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
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|}<br />
MOPP: '''<u>M</u>'''echlorethamine, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen variant #3, uncapped vincristine {{#subobject:ff7478|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.bloodjournal.org/content/42/2/163.long Young et al. 1973a]<br />
|1964-NR<br />
| style="background-color:#91cf61" |Non-randomized (RT)<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197610)38:4%3C1494::AID-CNCR2820380408%3E3.0.CO;2-E Kolygin 1976]<br />
|1970-1975<br />
| style="background-color:#91cf61" |Non-randomized (RT)<br />
|-<br />
|}<br />
==== Chemotherapy====<br />
*[[Mechlorethamine (Mustargen)]] 6 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 14<br />
'''28-day cycle for 6 to 8 cycles'''<br />
===References===<br />
#Young RC, DeVita VT, Johnson RE. Hodgkin's disease in childhood. Blood. 1973 Aug;42(2):163-74. [http://www.bloodjournal.org/content/42/2/163.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/4793108 PubMed]<br />
#Kolygin BA. Combination chemotherapy of Hodgkin's disease in children. Cancer. 1976 Oct;38(4):1494-7. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197610)38:4%3C1494::AID-CNCR2820380408%3E3.0.CO;2-E link to original article] [https://pubmed.ncbi.nlm.nih.gov/991072 PubMed]<br />
<br />
<br />
=Consolidation after upfront therapy=<br />
==C-MOPP {{#subobject:034931|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
C-MOPP: '''<u>C</u>'''yclophospha'''<u>M</u>'''ide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
<br>COPP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen variant #1, 2 cycles {{#subobject:cfcc4b|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
====Preceding treatment====<br />
*[[#OPPA|OPPA]] x 2<br />
====Chemotherapy====<br />
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
'''28-day cycle for 2 cycles'''<br />
===Regimen variant #2, 4 cycles {{#subobject:228db9|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
====Preceding treatment====<br />
*[[#OPPA|OPPA]] x 2<br />
====Chemotherapy====<br />
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
'''28-day cycle for 4 cycles'''<br />
===References===<br />
#'''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
==COPDAC {{#subobject:195ad7|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
COPDAC: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>DAC</u>'''arbazine<br />
===Regimen variant #1, 2 cycles {{#subobject:e9d06d|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
====Preceding treatment====<br />
*[[#OEPA|OEPA]] x 2<br />
====Chemotherapy====<br />
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Dacarbazine (DTIC)]] 250 mg/m<sup>2</sup> IV once per day on days 1 to 4<br />
'''28-day cycle for 2 cycles'''<br />
===Regimen variant #2, 4 cycles {{#subobject:515d30|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
====Preceding treatment====<br />
*[[#OEPA|OEPA]] x 2<br />
==== Chemotherapy====<br />
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Dacarbazine (DTIC)]] 250 mg/m<sup>2</sup> IV once per day on days 1 to 4<br />
'''28-day cycle for 4 cycles'''<br />
===References ===<br />
#'''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
<br />
<br />
=Maintenance after upfront therapy=<br />
==Bacillus Calmette-Guérin (BCG) monotherapy {{#subobject:e1fd72|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:52ca75|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.nejm.org/doi/full/10.1056/NEJM197412052912305 Sokal et al. 1974]<br />
|1965-1967<br />
| style="background-color:#91cf61" |Randomized, <20 pts in this subgroup (E-esc)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation_2|Observation]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
''Note: this study was open to patients with "malignant lymphoma" but the majority had Hodgkin disease.''<br />
==== Immunotherapy====<br />
*[[Bacillus Calmette-Guérin (BCG)]]<br />
===References===<br />
#Sokal JE, Aungst CW, Snyderman M. Delay in progression of malignant lymphoma after BCG vaccination. N Engl J Med. 1974 Dec 5;291(23):1226-30. [https://www.nejm.org/doi/full/10.1056/NEJM197412052912305 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4609380 PubMed]<br />
=Relapsed or refractory, salvage therapy =<br />
==ABDIC {{#subobject:c5c5ab|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABDIC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>DI</u>'''C (Dacarbazine), '''<u>C</u>'''CNU (Lomustine), Prednisone<br />
===Regimen {{#subobject:4ba1e1|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19801201)46:11%3C2349::AID-CNCR2820461105%3E3.0.CO;2-V/abstract Rodgers et al. 1980]<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Dacarbazine (DTIC)]]<br />
*[[Lomustine (CCNU)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
#Rodgers RW, Gamble JF, Loh KK, Shullenberger CC. Adriamycin, bleomycin, DIC, CCNU, and prednisone (ABDIC) chemotherapy in MOPP-resistant Hodgkin's disease. Cancer. 1980 Dec 1;46(11):2349-55. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19801201)46:11%3C2349::AID-CNCR2820461105%3E3.0.CO;2-V/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/6159961 PubMed]<br />
##'''Update:''' Tannir N, Hagemeister F, Velasquez W, Cabanillas F. Long-term follow-up with ABDIC salvage chemotherapy of MOPP-resistant Hodgkin's disease. J Clin Oncol. 1983 Jul;1(7):432-9. [https://doi.org/10.1200/jco.1983.1.7.432 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6199478 PubMed]<br />
==ABVD {{#subobject:c5a35d|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVD: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine<br />
===Regimen {{#subobject:ae32ee|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" | Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197806)41:6%3C2107::AID-CNCR2820410606%3E3.0.CO;2-L/abstract Krikorian et al. 1978]<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|[https://doi.org/10.1007/bf00254081 Santoro & Bonadonna 1979]<br />
| style="background-color:#91cf61" | Non-randomized<br />
|-<br />
|[http://annals.org/article.aspx?articleid=695320 Santoro et al. 1982a]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|[http://annals.org/article.aspx?articleid=698987 Harker et al. 1984]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
''This is for historical interest only; ABVD is no longer used in the salvage setting.''<br />
====Chemotherapy ====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Dacarbazine (DTIC)]]<br />
===References===<br />
#Krikorian JG, Portlock CS, Rosenberg SA. Treatment of advanced Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) after failure of MOPP therapy. Cancer. 1978 Jun;41(6):2107-11. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197806)41:6%3C2107::AID-CNCR2820410606%3E3.0.CO;2-L/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/77716 PubMed]<br />
#Santoro A, Bonadonna G. Prolonged disease-free survival in MOPP-resistant Hodgkin's disease after treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). Cancer Chemother Pharmacol. 1979;2(2):101-5. [https://doi.org/10.1007/bf00254081 link to original article] [https://pubmed.ncbi.nlm.nih.gov/93984 PubMed]<br />
#Santoro A, Bonfante V, Bonadonna G. Salvage chemotherapy with ABVD in MOPP-resistant Hodgkin's disease. Ann Intern Med. 1982 Feb;96(2):139-43. [http://annals.org/article.aspx?articleid=695320 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6174060 PubMed]<br />
#Harker WG, Kushlan P, Rosenberg SA. Combination chemotherapy for advanced Hodgkin's disease after failure of MOPP: ABVD and B-CAVe. Ann Intern Med. 1984 Oct;101(4):440-6. [http://annals.org/article.aspx?articleid=698987 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6206757 PubMed]<br />
==B-CAVe {{#subobject:41a31c|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
B-CAVe: '''<u>B</u>'''leomycin, '''<u>C</u>'''CNU (Lomustine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''inblastin'''<u>e</u>'''<br />
===Regimen {{#subobject:c53f0c|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197805)41:5%3C1670::AID-CNCR2820410504%3E3.0.CO;2-Y/abstract Porzig et al. 1978]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|[http://annals.org/article.aspx?articleid=698987 Harker et al. 1984]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Lomustine (CCNU)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Vinblastine (Velban)]]<br />
===References===<br />
#Porzig KJ, Portlock CS, Robertson A, Rosenberg SA. Treatment of advanced Hodgkin's disease with B-CAVE following MOPP failure. Cancer. 1978 May;41(5):1670-5. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197805)41:5%3C1670::AID-CNCR2820410504%3E3.0.CO;2-Y/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/77180 PubMed]<br />
#Harker WG, Kushlan P, Rosenberg SA. Combination chemotherapy for advanced Hodgkin's disease after failure of MOPP: ABVD and B-CAVe. Ann Intern Med. 1984 Oct;101(4):440-6. [http://annals.org/article.aspx?articleid=698987 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6206757 PubMed]<br />
==BVCPP {{#subobject:cb42cf|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
BVCPP: '''<u>B</u>'''CNU (Carmustine), '''<u>V</u>'''inblastine, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:514e7d|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142%28197811%2942%3A5%3C2101%3A%3AAID-CNCR2820420504%3E3.0.CO%3B2-M Durant et al. 1978]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Carmustine (BCNU)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
====Subsequent treatment====<br />
*Patients who achieved CR: No additional therapy versus [[Hodgkin_lymphoma#MOPP|MOPP]] x 6 versus BVCPP x 6 additional cycles<br />
===References===<br />
#Durant JR, Gams RA, Velez-Garcia E, Bartolucci A, Wirtschafter D, Dorfman R. BCNU, velban, cyclophosphamide, procarbazine, and prednisone (BVCPP) in advanced Hodgkin's disease. Cancer. 1978 Nov;42(5):2101-10. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142%28197811%2942%3A5%3C2101%3A%3AAID-CNCR2820420504%3E3.0.CO%3B2-M link to original article] [https://pubmed.ncbi.nlm.nih.gov/719600 PubMed]<br />
==BVDS {{#subobject:3a24f9|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
BVDS: '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''oxorubicin, '''<u>S</u>'''treptozocin<br />
===Regimen {{#subobject:41d09e|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://jamanetwork.com/journals/jama/article-abstract/350618 Vinciguerra et al. 1977]<br />
| style="background-color:#ffffbe" |Non-randomized, <20 pts<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Streptozocin (Zanosar)]]<br />
===References===<br />
#Vinciguerra V, Coleman M, Jarowski CI, Degnan TJ, Silver RT. A new combination chemotherapy for resistant Hodgkin disease. JAMA. 1977 Jan 3;237(1):33-5. [https://jamanetwork.com/journals/jama/article-abstract/350618 link to original article] [https://pubmed.ncbi.nlm.nih.gov/62854 PubMed]<br />
==CEP {{#subobject:a1a2cc|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
CEP: '''<u>C</u>'''CNU (Lomustine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednimustine<br />
===Regimen {{#subobject:a353e9|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://pubmed.ncbi.nlm.nih.gov/2420012 Santoro et al. 1986]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Lomustine (CCNU)]]<br />
*[[Etoposide (Vepesid)]]<br />
*[[Prednimustine (Stereocyt)]]<br />
===References===<br />
#Santoro A, Viviani S, Valagussa P, Bonfante V, Bonadonna G. CCNU, etoposide, and prednimustine (CEP) in refractory Hodgkin's disease. Semin Oncol. 1986 Mar;13(1 Suppl 1):23-6. [https://pubmed.ncbi.nlm.nih.gov/2420012 PubMed]<br />
==CVB {{#subobject:b2b2cc|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
CVB: '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''inblastine, '''<u>B</u>'''leomycin<br />
===Regimen {{#subobject:a464e9|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(75)92069-3/fulltext Goldman & Dawson 1975]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Lomustine (CCNU)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
===References===<br />
#Goldman JM, Dawson AA. Combination therapy for advanced resistant Hodgkin's disease. Lancet. 1975 Dec 20;2(7947):1224-7. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(75)92069-3/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/53720 PubMed]<br />
==CVPP {{#subobject:be8f99|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
CVPP: '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''inblastine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:f32d98|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.1986.4.6.838 Vinciguerra et al. 1986]<br />
|1975-1981<br />
| style="background-color:#1a9851" |Randomized (C)<br />
|1. [[#ABOS_99|ABOS]]<br> 2. [[#CVPP.2FABOS_99|CVPP/ABOS]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Lomustine (CCNU)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
#Vinciguerra V, Propert KJ, Coleman M, Anderson JR, Stutzman L, Pajak TF, Nissen NI, Frizzera G, Gottlieb A, Holland JF; [[Study_Groups#CALGB|CALGB]]. Alternating cycles of combination chemotherapy for patients with recurrent Hodgkin's disease following radiotherapy: a prospectively randomized study by the Cancer and Leukemia Group B. J Clin Oncol. 1986 Jun;4(6):838-46. [https://doi.org/10.1200/JCO.1986.4.6.838 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2423652 PubMed]<br />
==SCAB {{#subobject:04355f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
SCAB: '''<u>S</u>'''treptozocin, '''<u>C</u>'''CNU (Lomustine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin<br />
===Regimen {{#subobject:5c34db|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1002/mpo.2950030106 Levi et al. 1977]<br />
| style="background-color:#ffffbe" |Non-randomized, <20 pts<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Streptozocin (Zanosar)]]<br />
*[[Lomustine (CCNU)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
===References===<br />
#Levi JA, Wiernik PH, Diggs CH. Combination chemotherapy of advanced previously treated Hodgkin's disease with streptozotocin, CCNU, adriamycin and bleomycin. Med Pediatr Oncol. 1977;3(1):33-40. [https://doi.org/10.1002/mpo.2950030106 link to original article] [https://pubmed.ncbi.nlm.nih.gov/65727 PubMed]<br />
=Relapsed or refractory, further lines of therapy=<br />
==Carmustine monotherapy {{#subobject:f072cf|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:d61e28|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.nejm.org/doi/full/10.1056/NEJM197108262850902 Young et al. 1971]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Carmustine (BCNU)]]<br />
===References===<br />
#Young RC, DeVita VT Jr, Serpick AA, Canellos GP. Treatment of advanced Hodgkin's disease with (1,3 bis (2-chloroethyl)-1-nitrosourea) BCNU. N Engl J Med. 1971 Aug 26;285(9):475-9. [https://www.nejm.org/doi/full/10.1056/NEJM197108262850902 link to original article] [https://pubmed.ncbi.nlm.nih.gov/5558887 PubMed]<br />
==Doxorubicin & Lomustine {{#subobject:7e7049|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:e9f038|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://jamanetwork.com/journals/jama/article-abstract/355977 Williams & Einhorn 1977]<br />
| style="background-color:#ffffbe" |Non-randomized, <20 pts<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Lomustine (CCNU)]]<br />
===References===<br />
#Williams SD, Einhorn LH. Combination chemotherapy with doxorubicin and lomustine: treatment of refractory Hodgkin's disease. JAMA. 1977 Oct 10;238(15):1659-61. [https://jamanetwork.com/journals/jama/article-abstract/355977 link to original article] [https://pubmed.ncbi.nlm.nih.gov/578254 PubMed]<br />
==Sirolimus & Vorinostat {{#subobject:273a59|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:91d698|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1158/1078-0432.ccr-20-1215 Janku et al. 2020 (MDACC 2009-0729)]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
''This is a very heavily pre-treated cohort, median of 6 prior therapies; doses here are one level below MTD and are proposed as the ongoing doses to be studied.''<br />
====Targeted therapy====<br />
*[[Sirolimus (Rapamune)]] 4 mg PO once per day<br />
*[[Vorinostat (Zolinza)]] as follows:<br />
**Cycle 1: 300 mg PO once per day on days 7 to 28<br />
**Subsequent cycles: 300 mg PO once per day on days 1 to 28<br />
'''28-day cycles'''<br />
===References===<br />
#'''MDACC 2009-0729:''' Janku F, Park H, Call SG, Madwani K, Oki Y, Subbiah V, Hong DS, Naing A, Velez-Bravo VM, Barnes TG, Hagemeister FB, Falchook GS, Karp DD, Wheler JJ, Piha-Paul SA, Garrido-Laguna I, Shpall EJ, Fayad LE, Neelapu SS, Meric-Bernstam F, Kurzrock R, Fanale MA. Safety and Efficacy of Vorinostat Plus Sirolimus or Everolimus in Patients with Relapsed Refractory Hodgkin Lymphoma. Clin Cancer Res. 2020 Nov 1;26(21):5579-5587. Epub 2020 Oct 14. [https://doi.org/10.1158/1078-0432.ccr-20-1215 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33055173/ PubMed] NCT01087554<br />
[[Category:Hodgkin lymphoma regimens]]<br />
[[Category:Historical regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Aggressive lymphomas]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Classical_Hodgkin_lymphoma,_pediatric&diff=56351Classical Hodgkin lymphoma, pediatric2022-05-18T16:58:49Z<p>Wayneliang: added subject tag</p>
<hr />
<div>{{#lst:Section editor transclusions|peds}}<br />
<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big><br><br><br />
''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Hodgkin_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Hodgkin lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br><br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=4}}<br />
=Guidelines=<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)]<br />
=Upfront Therapy, High Risk=<br />
==ABVE-PC (COG AHOD1331)==<br />
===Standard Arm (ABVE-PC)===<br />
====Cycles 1 to 5====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once on days 1 & 2<br />
**Concentration not to exceed 2 mg/mL<br />
**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1 & 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3<br />
**Rate should not exceed 300 mg/m<sup>2</sup><br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO BID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 & 2<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV daily beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC > 1000/μL<br />
**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6<br />
Response evaluation after cycle 2<br />
'''21 day cycle'''<br />
===Experimental Arm (Bv-AVEPC)===<br />
====Cycles 1 to 5====<br />
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg (maximum dose of 180 mg) IV over 30 minutes once on day 1<br />
**[[Brentuximab vedotin (Adcetris)]] should be given prior to other chemotherapy<br />
**Do NOT use In Line Filters<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once on days 1 & 2<br />
**Concentration not to exceed 2 mg/mL<br />
**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 8<br />
**<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3<br />
**Rate should not exceed 300 mg/m<sup>2</sup><br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO BID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 & 2<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV daily beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC > 1000/μL<br />
**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6<br />
Response evaluation after cycle 2<br />
'''21 day cycle'''<br />
===References===<br />
# '''COG AHOD1331:''' Mailhot Vega RB, Castellino SM, Pei Q, Parsons S, Roberts KB, Hodgson D, Charpentier AM, Fitzgerald TJ, Kessel SK, Keller FG, Kelly K, and Hoppe BS. Evaluating Disparities in Proton Radiation Therapy Use in AHOD1331, A Contemporary Children's Oncology Group Trial for Advanced-Stage Hodgkin Lymphoma. Int J Part Ther. 2021 Oct 28;8(3):55-57. [https://doi.org/10.14338/ijpt-21-00012.1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8768892/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35127976/ PubMed] NCT02166463<br />
=Upfront Therapy, Intermediate Risk=<br />
==ABVE-PC (COG AHOD0031) {{#subobject:c24d93|Regimen=1}}==<br />
===Rapid Early Responders (Standard Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====Involved Field Radiation Therapy====<br />
===Rapid Early Responders (Reduced Therapy Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====No Further Treatment====<br />
===Slow Early Responders (Standard Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
===Slow Early Responders (Augmented Therapy Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Therapy====<br />
====DECA Therapy x 2 Cycles====<br />
=====Chemotherapy=====<br />
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2<br />
**[[Dexamethasone (Decadron)]] to be given prior to [[Etoposide (Vepesid)]]/[[Cytarabine (Ara-C)]]<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 2<br />
**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL<br />
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours on days 1, 2<br />
**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL<br />
*[[Cisplatin (Platinol)]] 90 mg/m<sup>2</sup> IV over 6 hours once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
====References====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
=Upfront Therapy, Low Risk=<br />
==OEPA (GPOD-HD-2002) {{#subobject:0e614f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)<br />
===Regimen {{#subobject:25c262|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.''<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Treatment group 2: [[#COPDAC|COPDAC]] x 2<br />
*Treatment group 3: [[#COPDAC|COPDAC]] x 4<br />
===References===<br />
# '''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
= Intermediate Risk Pediatric Hodgkin Lymphoma =<br />
==ABVE-PC {{#subobject:c24d93|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
===Regimen variant #1, 2 cycles with response adaptation {{#subobject:7fa6ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
'''21-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total) versus DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2; then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #2, 3 cycles with response adaptation {{#subobject:14cd95|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 3 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (5 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #3, 4 cycles with response adaptation {{#subobject:17a940|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 2<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
'''21-day cycle for 4 cycles, including the first 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders with CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Rapid early responders with less than CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #4, 5 cycles {{#subobject:7e95ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old, who are slow early responders. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 3, with slow early response<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 5 cycles, including the first 3 cycles'''<br />
====Subsequent treatment====<br />
*[[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===References===<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
= Radiation therapy {{#subobject:b169ea|Regimen=1}}=<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy<br />
===Regimen variant #2, 21 Gy of IFRT {{#subobject:dfa48c|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2002.12.007 Nachman et al. 2002 (CCG 5942)]<br />
|1995-1998<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
|1997-2001<br />
| style="background-color:#91cf61" |Phase 2<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
|2002-2009<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS48<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old.''<br />
====Preceding treatment====<br />
*CCG 5942: [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification<br />
*POG P9425: [[#ABVE-PC|ABVE-PC]] x 3 to 5<br />
*COG AHOD0031 RERs: [[#ABVE-PC|ABVE-PC]] x 4<br />
*COG AHOD0031 SERs: [[#ABVE-PC|ABVE-PC]] x 4 versus [[#ABVE-PC|ABVE-PC]] x 2, then DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2<br />
====Radiotherapy====<br />
*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.5 to 1.75 Gy per fraction<br />
===References===<br />
# '''CCG 5942:''' Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12228196 PubMed] NCT00592111<br />
## '''Update:''' Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136 PubMed]<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
[[Category:Hodgkin lymphoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Aggressive lymphomas]]<br />
[[Category:Pediatric hematologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Classical_Hodgkin_lymphoma,_pediatric&diff=56350Classical Hodgkin lymphoma, pediatric2022-05-18T16:54:37Z<p>Wayneliang: remove duplicated content</p>
<hr />
<div>{{#lst:Section editor transclusions|peds}}<br />
<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big><br><br><br />
''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Hodgkin_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Hodgkin lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br><br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=4}}<br />
=Guidelines=<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)]<br />
=Upfront Therapy, High Risk=<br />
==ABVE-PC (COG AHOD1331)==<br />
===Standard Arm (ABVE-PC)===<br />
====Cycles 1 to 5====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once on days 1 & 2<br />
**Concentration not to exceed 2 mg/mL<br />
**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1 & 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3<br />
**Rate should not exceed 300 mg/m<sup>2</sup><br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO BID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 & 2<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV daily beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC > 1000/μL<br />
**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6<br />
Response evaluation after cycle 2<br />
'''21 day cycle'''<br />
===Experimental Arm (Bv-AVEPC)===<br />
====Cycles 1 to 5====<br />
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg (maximum dose of 180 mg) IV over 30 minutes once on day 1<br />
**[[Brentuximab vedotin (Adcetris)]] should be given prior to other chemotherapy<br />
**Do NOT use In Line Filters<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once on days 1 & 2<br />
**Concentration not to exceed 2 mg/mL<br />
**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 8<br />
**<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3<br />
**Rate should not exceed 300 mg/m<sup>2</sup><br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO BID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 & 2<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV daily beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC > 1000/μL<br />
**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6<br />
Response evaluation after cycle 2<br />
'''21 day cycle'''<br />
===References===<br />
# '''COG AHOD1331:''' Mailhot Vega RB, Castellino SM, Pei Q, Parsons S, Roberts KB, Hodgson D, Charpentier AM, Fitzgerald TJ, Kessel SK, Keller FG, Kelly K, and Hoppe BS. Evaluating Disparities in Proton Radiation Therapy Use in AHOD1331, A Contemporary Children's Oncology Group Trial for Advanced-Stage Hodgkin Lymphoma. Int J Part Ther. 2021 Oct 28;8(3):55-57. [https://doi.org/10.14338/ijpt-21-00012.1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8768892/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35127976/ PubMed] NCT02166463<br />
=Upfront Therapy, Intermediate Risk=<br />
==ABVE-PC (COG AHOD0031)==<br />
===Rapid Early Responders (Standard Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====Involved Field Radiation Therapy====<br />
===Rapid Early Responders (Reduced Therapy Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====No Further Treatment====<br />
===Slow Early Responders (Standard Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
===Slow Early Responders (Augmented Therapy Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Therapy====<br />
====DECA Therapy x 2 Cycles====<br />
=====Chemotherapy=====<br />
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2<br />
**[[Dexamethasone (Decadron)]] to be given prior to [[Etoposide (Vepesid)]]/[[Cytarabine (Ara-C)]]<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 2<br />
**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL<br />
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours on days 1, 2<br />
**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL<br />
*[[Cisplatin (Platinol)]] 90 mg/m<sup>2</sup> IV over 6 hours once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
====References====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
=Upfront Therapy, Low Risk=<br />
==OEPA (GPOD-HD-2002) {{#subobject:0e614f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)<br />
===Regimen {{#subobject:25c262|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.''<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Treatment group 2: [[#COPDAC|COPDAC]] x 2<br />
*Treatment group 3: [[#COPDAC|COPDAC]] x 4<br />
===References===<br />
# '''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
= Intermediate Risk Pediatric Hodgkin Lymphoma =<br />
==ABVE-PC {{#subobject:c24d93|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
===Regimen variant #1, 2 cycles with response adaptation {{#subobject:7fa6ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
'''21-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total) versus DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2; then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #2, 3 cycles with response adaptation {{#subobject:14cd95|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 3 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (5 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #3, 4 cycles with response adaptation {{#subobject:17a940|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 2<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
'''21-day cycle for 4 cycles, including the first 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders with CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Rapid early responders with less than CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #4, 5 cycles {{#subobject:7e95ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old, who are slow early responders. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 3, with slow early response<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 5 cycles, including the first 3 cycles'''<br />
====Subsequent treatment====<br />
*[[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===References===<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
= Radiation therapy {{#subobject:b169ea|Regimen=1}}=<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy<br />
===Regimen variant #2, 21 Gy of IFRT {{#subobject:dfa48c|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2002.12.007 Nachman et al. 2002 (CCG 5942)]<br />
|1995-1998<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
|1997-2001<br />
| style="background-color:#91cf61" |Phase 2<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
|2002-2009<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS48<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old.''<br />
====Preceding treatment====<br />
*CCG 5942: [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification<br />
*POG P9425: [[#ABVE-PC|ABVE-PC]] x 3 to 5<br />
*COG AHOD0031 RERs: [[#ABVE-PC|ABVE-PC]] x 4<br />
*COG AHOD0031 SERs: [[#ABVE-PC|ABVE-PC]] x 4 versus [[#ABVE-PC|ABVE-PC]] x 2, then DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2<br />
====Radiotherapy====<br />
*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.5 to 1.75 Gy per fraction<br />
===References===<br />
# '''CCG 5942:''' Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12228196 PubMed] NCT00592111<br />
## '''Update:''' Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136 PubMed]<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
[[Category:Hodgkin lymphoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Aggressive lymphomas]]<br />
[[Category:Pediatric hematologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Classical_Hodgkin_lymphoma,_pediatric&diff=56349Classical Hodgkin lymphoma, pediatric2022-05-18T16:52:35Z<p>Wayneliang: Reorganizing headers</p>
<hr />
<div>{{#lst:Section editor transclusions|peds}}<br />
<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big><br><br><br />
''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Hodgkin_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Hodgkin lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br><br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=4}}<br />
=Guidelines=<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)]<br />
<br />
=Upfront Therapy, High Risk=<br />
==ABVE-PC (COG AHOD1331)==<br />
===Standard Arm (ABVE-PC)===<br />
====Cycles 1 to 5====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once on days 1 & 2<br />
**Concentration not to exceed 2 mg/mL<br />
**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1 & 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3<br />
**Rate should not exceed 300 mg/m<sup>2</sup><br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO BID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 & 2<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV daily beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC > 1000/μL<br />
**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6<br />
<br />
Response evaluation after cycle 2<br />
<br />
'''21 day cycle'''<br />
<br />
===Experimental Arm (Bv-AVEPC)===<br />
====Cycles 1 to 5====<br />
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg (maximum dose of 180 mg) IV over 30 minutes once on day 1<br />
**[[Brentuximab vedotin (Adcetris)]] should be given prior to other chemotherapy<br />
**Do NOT use In Line Filters<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push or intermittent infusion once on days 1 & 2<br />
**Concentration not to exceed 2 mg/mL<br />
**IV push over 1 to 5 minutes or by intermittent infusion over 1 to 15 minutes; may prolong to 60 minutes if institutional policies mandate<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once on day 8<br />
**<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 60 to 120 minutes once per day on days 1 to 3<br />
**Rate should not exceed 300 mg/m<sup>2</sup><br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup> PO BID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV over 30 to 60 minutes once on day 1 & 2<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC (preferred) or IV daily beginning on day 4, 5, 6, 7, 8, or 9, per institutional policy and continuing until ANC > 1000/μL<br />
**Alternative: [[Pegfilgrastim (Neulasta)]] 100 mcg/kg (Maximum dose of 6 mg) SC once on day 4, 5, or 6<br />
<br />
Response evaluation after cycle 2<br />
<br />
'''21 day cycle'''<br />
<br />
===References===<br />
# '''COG AHOD1331:''' Mailhot Vega RB, Castellino SM, Pei Q, Parsons S, Roberts KB, Hodgson D, Charpentier AM, Fitzgerald TJ, Kessel SK, Keller FG, Kelly K, and Hoppe BS. Evaluating Disparities in Proton Radiation Therapy Use in AHOD1331, A Contemporary Children's Oncology Group Trial for Advanced-Stage Hodgkin Lymphoma. Int J Part Ther. 2021 Oct 28;8(3):55-57. [https://doi.org/10.14338/ijpt-21-00012.1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8768892/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35127976/ PubMed] NCT02166463<br />
<br />
=Upfront Therapy, Intermediate Risk=<br />
==ABVE-PC (COG AHOD0031)==<br />
===Rapid Early Responders (Standard Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
====Evaluate Response====<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
====Evaluate Response====<br />
====Involved Field Radiation Therapy====<br />
<br />
===Rapid Early Responders (Reduced Therapy Arm)===<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
====Evaluate Response====<br />
<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
====No Further Treatment====<br />
<br />
===Slow Early Responders (Standard Arm)===<br />
<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
====Evaluate Response====<br />
<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
====Evaluate Response====<br />
<br />
===Slow Early Responders (Augmented Therapy Arm)===<br />
<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
====Evaluate Therapy====<br />
<br />
====DECA Therapy x 2 Cycles====<br />
<br />
=====Chemotherapy=====<br />
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV over 15 minutes on days 1, 2<br />
**[[Dexamethasone (Decadron)]] to be given prior to [[Etoposide (Vepesid)]]/[[Cytarabine (Ara-C)]]<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 2 <br />
**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL<br />
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 3 hours on days 1, 2<br />
**Mix [[Etoposide (Vepesid)]] with [[Cytarabine (Ara-C)]] in D5W at an [[Etoposide (Vepesid)]] concentration of ≤ 0.4 mg/mL<br />
*[[Cisplatin (Platinol)]] 90 mg/m<sup>2</sup> IV over 6 hours once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
=====References=====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
====ABVE-PC x 2 Cycles====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 10 to 30 minutes once per day on days 1, 2<br />
*[[Bleomycin (Blenoxane)]] 5 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV over 10 to 20 minutes or SQ once on day 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 1, 8<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 2, 3<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO divided BID or TID on days 1 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 1 hour once on day 1<br />
'''21-day cycle for 2 cycles'''<br />
====References====<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
=Upfront Therapy, Low Risk=<br />
==OEPA (GPOD-HD-2002) {{#subobject:0e614f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)<br />
===Regimen {{#subobject:25c262|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.''<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Treatment group 2: [[#COPDAC|COPDAC]] x 2<br />
*Treatment group 3: [[#COPDAC|COPDAC]] x 4<br />
===References===<br />
# '''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
<br />
= Intermediate Risk Pediatric Hodgkin Lymphoma =<br />
<br />
==ABVE-PC {{#subobject:c24d93|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
===Regimen variant #1, 2 cycles with response adaptation {{#subobject:7fa6ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
'''21-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total) versus DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2; then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #2, 3 cycles with response adaptation {{#subobject:14cd95|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 3 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (5 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #3, 4 cycles with response adaptation {{#subobject:17a940|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 2<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
'''21-day cycle for 4 cycles, including the first 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders with CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Rapid early responders with less than CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #4, 5 cycles {{#subobject:7e95ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old, who are slow early responders. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 3, with slow early response<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 5 cycles, including the first 3 cycles'''<br />
====Subsequent treatment====<br />
*[[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===References===<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
= High Risk Pediatric Hodgkin Lymphoma =<br />
<br />
== ABVE-PC (COG AHOD1331 Standard Arm) ==<br />
<br />
=Radiation therapy {{#subobject:b169ea|Regimen=1}}=<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy<br />
===Regimen variant #2, 21 Gy of IFRT {{#subobject:dfa48c|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2002.12.007 Nachman et al. 2002 (CCG 5942)]<br />
|1995-1998<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
|1997-2001<br />
| style="background-color:#91cf61" |Phase 2<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
|2002-2009<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS48<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old.''<br />
====Preceding treatment====<br />
*CCG 5942: [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification<br />
*POG P9425: [[#ABVE-PC|ABVE-PC]] x 3 to 5<br />
*COG AHOD0031 RERs: [[#ABVE-PC|ABVE-PC]] x 4<br />
*COG AHOD0031 SERs: [[#ABVE-PC|ABVE-PC]] x 4 versus [[#ABVE-PC|ABVE-PC]] x 2, then DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2<br />
====Radiotherapy====<br />
*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.5 to 1.75 Gy per fraction<br />
===References===<br />
# '''CCG 5942:''' Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12228196 PubMed] NCT00592111<br />
## '''Update:''' Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136 PubMed]<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
[[Category:Hodgkin lymphoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Aggressive lymphomas]]<br />
[[Category:Pediatric hematologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Anaplastic_large_cell_lymphoma,_pediatric&diff=56347Anaplastic large cell lymphoma, pediatric2022-05-17T20:58:08Z<p>Wayneliang: /* HOP */ changed to APO</p>
<hr />
<div>{{#lst:Section editor transclusions|peds}}<br />
<big>''This page contains studies that were specific to pediatric populations. For the more general ALCL page, follow [[Anaplastic large cell lymphoma|this link]].</big><br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=3}}<br />
=Untreated=<br />
==COG ANHL12P1 protocol {{#subobject:69ug1e|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Protocol {{#subobject:1yxa91|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1182/blood.2020009806 Lowe et al. 2021 (COG ANHL12P1)]<br />
|2013-2017<br />
| style="background-color:#91cf61" |Randomized Phase 2<br />
|-<br />
|}<br />
''Note: there appear to be several dosing errors in Table 2; the authors have been contacted for clarification.''<br />
====Chemotherapy, prophase====<br />
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV once per day on days 1 & 2<br />
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup>/day PO on days 1 & 2, then 10 mg/m<sup>2</sup>/day PO on days 3 to 5<br />
====CNS prophylaxis====<br />
*[[Methotrexate (MTX)]] age-based IT once on day 1<br />
'''5-day course'''<br />
====Antibody-drug conjugate therapy, induction====<br />
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg (maximum dose of 180 mg) IV over 30 minutes once on day 1<br />
====Chemotherapy, induction====<br />
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1<br />
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 1 to 5<br />
*[[Ifosfamide (Ifex)]] as follows:<br />
**Cycles 1, 3, 5: 800 mg/m<sup>2</sup> IV once per day on days 1 to 5<br />
*[[Etoposide (Vepesid)]] as follows:<br />
**Cycles 1, 3, 5: 100 mg/m<sup>2</sup> IV once per day on days 4 & 5<br />
*[[Cytarabine (Ara-C)]] as follows:<br />
**Cycles 1, 3, 5: 150 mg/m<sup>2</sup> IV every 12 hours on days 4 & 5 (total dose per cycle: 600 mg/m<sup>2</sup>)<br />
*[[Cyclophosphamide (Cytoxan)]] as follows:<br />
**Cycles 2, 4, 6: 200 mg/m<sup>2</sup> IV once per day on days 1 to 5<br />
*[[Doxorubicin (Adriamycin)]] as follows:<br />
**Cycles 2, 4, 6: 25 mg/m<sup>2</sup> IV once per day on days 4 & 5<br />
'''21-day cycle for 6 cycles'''<br />
===References===<br />
#'''COG ANHL12P1:''' Lowe EJ, Reilly AF, Lim MS, Gross TG, Saguilig L, Barkauskas DA, Wu R, Alexander S, Bollard CM. Brentuximab vedotin in combination with chemotherapy for pediatric patients with ALK+ ALCL: results of COG trial ANHL12P1. Blood. 2021 Jul 1;137(26):3595-3603. [https://doi.org/10.1182/blood.2020009806 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33684925/ PubMed] NCT01979536<br />
==EICNHL ALCL99 protocol {{#subobject:69ug1e|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Protocol {{#subobject:1yxa91|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 17%"|Study<br />
!style="width: 15%"|Years of enrollment<br />
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 17%"|Comparator<br />
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2008.18.1487 Brugières et al. 2009 (EICNHL ALCL99)]<br />
|1999-2005<br />
| style="background-color:#1a9851" |Randomized (E-switch-ic)<br />
|[[#EICNHL_ALCL99_protocol|EICHNL ALCL99]]; alternate MTX dosing<br />
| style="background-color:#ffffbf" |Inconclusive whether non-inferior EFS<br />
| style="background-color:#1a9850" |Less toxic<br />
|-<br />
|}<br />
====Chemotherapy, prophase====<br />
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV once per day on days 1 & 2<br />
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup>/day PO on days 1 & 2, then 10 mg/m<sup>2</sup>/day PO on days 3 to 5<br />
====CNS prophylaxis====<br />
*Triple-therapy IT once on day 1<br />
'''5-day course'''<br />
====Chemotherapy, induction====<br />
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1<br />
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 1 to 5<br />
*[[Ifosfamide (Ifex)]] as follows:<br />
**Cycles 1, 3, 5: 800 mg/m<sup>2</sup> IV once per day on days 1 to 5<br />
*[[Etoposide (Vepesid)]] as follows:<br />
**Cycles 1, 3, 5: 100 mg/m<sup>2</sup> IV once per day on days 4 & 5<br />
*[[Cytarabine (Ara-C)]] as follows:<br />
**Cycles 1, 3, 5: 150 mg/m<sup>2</sup> IV every 12 hours on days 4 & 5 (total dose per cycle: 600 mg/m<sup>2</sup>)<br />
*[[Cyclophosphamide (Cytoxan)]] as follows:<br />
**Cycles 2, 4, 6: 200 mg/m<sup>2</sup> IV once per day on days 1 to 5<br />
*[[Doxorubicin (Adriamycin)]] as follows:<br />
**Cycles 2, 4, 6: 25 mg/m<sup>2</sup> IV once per day on days 4 & 5<br />
'''21-day cycle for 6 cycles'''<br />
===References===<br />
#'''EICNHL ALCL99:''' Brugières L, Le Deley MC, Rosolen A, Williams D, Horibe K, Wrobel G, Mann G, Zsiros J, Uyttebroeck A, Marky I, Lamant L, Reiter A. Impact of the methotrexate administration dose on the need for intrathecal treatment in children and adolescents with anaplastic large-cell lymphoma: results of a randomized trial of the EICNHL Group. J Clin Oncol. 2009 Feb 20;27(6):897-903. Epub 2009 Jan 12. [https://doi.org/10.1200/jco.2008.18.1487 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/19139435/ PubMed] NCT00006455<br />
==APO{{#subobject:6964de|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
APO: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine)<br />
<br />
HOP: '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone<br />
<br><br />
===Regimen {{#subobject:985a91|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682366/ Alexander et al. 2014 (COG ANHL0131)]<br />
|2004-2008<br />
| style="background-color:#91cf61" |Non-randomized portion of phase III RCT<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV once per day on days 1 & 22<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO on days 1 to 28<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22, 29<br />
====CNS prophylaxis====<br />
*[[Methotrexate (MTX)]] age-adjusted IT once per day on days 1, 8, 22<br />
'''6-week course'''<br />
====Subsequent treatment====<br />
*APO versus APV maintenance<br />
===References===<br />
# '''COG ANHL0131:''' Alexander S, Kraveka JM, Weitzman S, Lowe E, Smith L, Lynch JC, Chang M, Kinney MC, Perkins SL, Laver J, Gross TG, Weinstein H. Advanced stage anaplastic large cell lymphoma in children and adolescents: results of ANHL0131, a randomized phase III trial of APO versus a modified regimen with vinblastine: a report from the children's oncology group. Pediatr Blood Cancer. 2014 Dec;61(12):2236-42. Epub 2014 Aug 23. [https://onlinelibrary.wiley.com/doi/abs/10.1002/pbc.25187 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682366/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/25156886 PubMed] NCT00059839<br />
=Relapsed or refractory, subsequent lines of therapy=<br />
==Crizotinib monotherapy {{#subobject:be5391|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:e9c195|Variant=1}}===<br />
{| class="wikitable" style="color:white; background-color:#404040"<br />
|<small>'''FDA-recommended dose'''</small><br />
|-<br />
|}<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730818/ Mossé et al. 2013 (ADVL0912)]<br />
|2009-2012<br />
| style="background-color:#91cf61" |Non-randomized (RT)<br />
|-<br />
|}<br />
''Note: this was an expansion cohort of a phase I study.''<br />
====Biomarker eligibility criteria====<br />
*ALK rearrangement<br />
====Targeted therapy====<br />
*[[Crizotinib (Xalkori)]] 280 mg/m<sup>2</sup> PO twice per day<br />
'''28-day cycles'''<br />
===References===<br />
# '''ADVL0912:''' Mossé YP, Lim MS, Voss SD, Wilner K, Ruffner K, Laliberte J, Rolland D, Balis FM, Maris JM, Weigel BJ, Ingle AM, Ahern C, Adamson PC, Blaney SM. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: a Children's Oncology Group phase 1 consortium study. Lancet Oncol. 2013 May;14(6):472-80. Epub 2013 Apr 16. [https://doi.org/10.1016/s1470-2045(13)70095-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730818/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/23598171 PubMed] NCT00939770<br />
[[Category:Anaplastic large cell lymphoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:T-cell lymphomas]]<br />
[[Category:Pediatric hematologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Medulloblastoma&diff=55608Medulloblastoma2022-04-14T21:20:18Z<p>Wayneliang: removed adjuvant label</p>
<hr />
<div>{{#lst:Section editor transclusions|peds-neuro}}<br />
''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[Medulloblastoma_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''<br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=4}}<br />
<br />
<br />
=Upfront Therapy=<br />
==COG ACNS0331 Standard Dose CSRT/Reduced Volume Boost to Tumor Bed==<br />
*Ages 3+<br />
*All patients must begin therapy within 31 days of surgery. <br />
===Chemoradiotherapy===<br />
====XRT====<br />
*Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions<br />
*Tumor Bed Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 8, 15, 22, 29, 36, 43 (Once a week starting one week after CSRT begins)<br />
**Round vincristine '''down''' to the nearest 0.1 mg<br />
'''7-week course'''<br />
===Maintenance Regimen A===<br />
Cycles 1, 2, 4, 5, 7, 8<br />
====Chemotherapy====<br />
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1<br />
*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)<br />
**[[Pediatric Lomustine Dosing Chart]]<br />
**Give [[Lomustine (CCNU)]] with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15<br />
**Dose rounded '''down''' to the nearest 0.1 mg<br />
**Can be given IV push over 1-minute or by infusion via minibag as per institution policy<br />
'''6-week cycle'''<br />
<br />
<br />
===Maintenance Regimen B===<br />
Cycles 3, 6, and 9<br />
====Chemotherapy====<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1, 2<br />
*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV over 15 to 30 minutes on Days 1, 2<br />
**Dose is given at least 15 minutes prior to or at the same time as [[Cyclophosphamide (Cytoxan)]] and repeated at 4 and 8 hours post [[Cyclophosphamide (Cytoxan)]]<br />
**Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as [[Cyclophosphamide (Cytoxan)]] and finished no sooner than 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8<br />
**Dose rounded '''down''' to the nearest 0.1 mg<br />
**Can be given IV push over 1-minute or by infusion via minibag as per institution policy<br />
'''6-week course'''<br />
=====References=====<br />
#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. [https://doi.org/10.1200/JCO.20.02730 link to original article] NCT00085735<br />
==COG ACNS0331 Standard Dose CSRT/Standard Volume Boost==<br />
*Ages 3+<br />
*All patients must begin therapy within 31 days of surgery. <br />
===Chemoradiotherapy===<br />
====XRT====<br />
*Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions<br />
*Posterior Fossa Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 8, 15, 22, 29, 36, 43 (Once a week starting one week after CSRT begins)<br />
**Round vincristine '''down''' to the nearest 0.1 mg<br />
'''7-week course'''<br />
===Maintenance Regimen A===<br />
Cycles 1, 2, 4, 5, 7, 8<br />
====Chemotherapy====<br />
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1<br />
*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V)<br />
**[[Pediatric Lomustine Dosing Chart]]<br />
**Give [[Lomustine (CCNU)]] with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15<br />
**Dose rounded '''down''' to the nearest 0.1 mg<br />
**Can be given IV push over 1-minute or by infusion via minibag as per institution policy<br />
'''6-week cycle'''<br />
===Maintenance Regimen B===<br />
Cycles 3, 6, and 9<br />
====Chemotherapy====<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1, 2<br />
*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup> IV over 15 to 30 minutes on Days 1, 2<br />
**Dose given at least 15 minutes prior to or at the same time as [[Cyclophosphamide (Cytoxan)]] and repeated at 4 and 8 hours post [[Cyclophosphamide (Cytoxan)]]<br />
**Can be given via continuous infusion starting 15 to 30 minutes before or at the same time as [[Cyclophosphamide (Cytoxan)]] and finished no sooner than 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8<br />
**Dose rounded '''down''' to the nearest 0.1 mg<br />
**Can be given IV push over 1-minute or by infusion via minibag as per institution policy<br />
'''6-week course'''<br />
====References====<br />
#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. [https://doi.org/10.1200/JCO.20.02730 link to original article] NCT00085735<br />
==COG ACNS0332 Regimen A==<br />
===Chemoradiotherapy===<br />
====XRT====<br />
*Craniospinal [[External beam radiotherapy]] 36 Gy in 20 daily fractions (Monday - Friday)<br />
*Posterior Fossa Boost [[External beam radiotherapy]] 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy)<br />
For additional boost details, such as technique and location, please see the full protocol as this depends on the site of metastases and disease stage<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15, 22, 29, 36 (Once a week starting within one week of the start of CSRT)<br />
**Round vincristine '''down''' to the nearest 0.1 mg<br />
'''6-Week Course'''<br />
===Maintenance Cycle===<br />
Begin each cycle on Day 29 and when ANC ≥ 750/μL, platelets ≥ 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours for a total of 6 cycles. <br />
====Chemotherapy====<br />
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on days 1, 8<br />
**Round vincristine '''down''' to the nearest 0.1 mg<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 1 hour once on days 2, 3<br />
**[[Cyclophosphamide (Cytoxan)]] should be given at least 24 hours after Cisplatin on day 2<br />
'''28-Day Course'''<br />
=====References=====<br />
#'''COG ACNS0332:''' Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. [https://doi.org/10.1200/jco.2017.76.4720 link to original article] NCT00392327<br />
#'''COG ACNS0332:''' Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] NCT00392327<br />
==COG ACNS0332 Regimen B==<br />
===Chemoradiotherapy===<br />
====XRT====<br />
*Craniospinal [[External beam radiotherapy]] 36 Gy in 20 daily fractions (Monday - Friday)<br />
*Posterior Fossa Boost [[External beam radiotherapy]] 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy)<br />
For additional boost details, such as technique and location, please see the full protocol as this depends on the site of metastases and disease stage<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15, 22, 29, 36 (Once a week starting within one week of the start of CSRT)<br />
**Round vincristine '''down''' to the nearest 0.1 mg<br />
**Administer prior to Carboplatin<br />
*[[Carboplatin (Paraplatin)]] 35 mg/m<sup>2</sup> IV over 15 minutes given daily 1 to 4 hours prior to radiation therapy (Total of 30 doses)<br />
**[[Carboplatin (Paraplatin)]] first dose administered on the first day of radiation therapy<br />
**[[Carboplatin (Paraplatin)]] should be '''HELD''' if radiation treatment is not given<br />
**Since there are 31 fractions of radiation, No [[Carboplatin (Paraplatin)]] should be given prior to the final radiation fraction<br />
'''6-Week Course'''<br />
===Maintenance Cycle===<br />
Begin each cycle on Day 29 and when ANC ≥ 750/μL, platelets ≥ 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours for a total of 6 cycles. <br />
====Chemotherapy====<br />
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on days 1, 8<br />
**Round vincristine '''down''' to the nearest 0.1 mg<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 1 hour once on days 2, 3<br />
**[[Cyclophosphamide (Cytoxan)]] should be given at least 24 hours after Cisplatin on day 2<br />
'''28-Day Course'''<br />
===References===<br />
#'''COG ACNS0332:''' Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. [https://doi.org/10.1200/jco.2017.76.4720 link to original article] NCT00392327<br />
#'''COG ACNS0332:''' Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] NCT00392327<br />
<br />
<br />
==COG ACNS0334 Regimen A==<br />
===Induction===<br />
====Chemotherapy====<br />
'''3 Cycles'''<br />
*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum single dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on Day 1, 8, 15<br />
<br />
*[[Etoposide (Vepesid)]] 2.5 mg/kg (maximum concentration of [[Etoposide (Vepesid)]] is 0.4 mg/ml) IV over 1 hour once daily on Day 1, 2, 3<br />
**Begin [[Etoposide (Vepesid)]] infusion 1 hour before the [[Cyclophosphamide (Cytoxan)]] or [[Cisplatin (Platinol)]] infusions<br />
<br />
*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV over 1 hour (Hour 1-2) on Days 1, 2 with hyperhydration and [[Mesna (Mesnex)]]<br />
**Must reduce urine specific gravity to ≤ 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour<br />
<br />
*[[Mesna (Mesnex)]] 60 mg/kg IV on Days 1, 2, of which the total daily [[Mesna (Mesnex)]] dose is administered in 5 equally divided doses of 12 mg/kg:<br />
**Dose 1: Initial bolus dose of mesna may be administered before or at the same time as the [[Cyclophosphamide (Cytoxan)]]<br />
**Dose 2: A 3-hour infusion of [[Mesna (Mesnex)]] immediately following the [[Cyclophosphamide (Cytoxan)]] infusion (Hours 2 - 5)<br />
**Dose 3-5: 3 subsequent [[Mesna (Mesnex)]] bolus doses are given at hours 6, 9, 12, or by institutional protocol<br />
**[[Mesna (Mesnex)]] may also be given as a 24-hour continuous infusion starting 30 minutes before cyclophosphamide and finishing no sooner than 12 hours after the end of the cyclophosphamide infusion, or by institutional protocol<br />
<br />
*[[Cisplatin (Platinol)]] 3.5 mg/kg IV infusion over 6 hours on Day 3<br />
**[[Cisplatin (Platinol)]] doses may require the use of mannitol to augment hydration and diuresis<br />
**Must reduce urine specific gravity to ≤1.010 prior to starting of [[Cisplatin (Platinol)] <br />
'''21 Day Course'''<br />
===Consolidation===<br />
====Chemotherapy====<br />
'''3 Cycles'''<br />
*[[Carboplatin (Paraplatin)]] 17 mg/kg IV over 2 hours given daily on Days 1 & 2<br />
** If corrected GFR is < 100 ml/min/1.73m<sup>2</sup>, the [[Carboplatin (Paraplatin)]] dose should be calculated using the modified Calvert formula<br />
<br />
*[[Thiotepa (Thioplex)]] 10 mg/kg IV over 2 hours once daily on Days 1 & 2 immediately following [[Carboplatin (Paraplatin)]] administration<br />
** Skincare, frequent bathing, and linen changes during [[Thiotepa (Thioplex)]] administration are important and required to avoid chemical skin burns<br />
<br />
*[[Filgrastim (Neupogen)]] 5 μg/kg SubQ or IV (per institutional policy) once daily starting on Day 5 (24 hours after infusion of PBSC) and continue until ANC > 2000/μL<br />
**If [[Filgrastim (Neupogen)]] is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion <br />
'''28-Day Course'''<br />
=====References=====<br />
#'''COG ACNS0334:''' P.D. Aridgides, G. Kang, C. Mazewski, T.E. Merchant. Outcomes after Radiation Therapy for Very Young Children with High-Risk Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor Treated on COG ACNS0334. Radiation Oncology 105, no. 1 (September 1, 2019)[https://doi.org/10.1016/j.ijrobp.2019.06.602 link to original article] NCT00336024<br />
==COG ACNS0334 Regimen B==<br />
===Induction===<br />
====Chemotherapy====<br />
'''3 Cycles'''<br />
*[[Vincristine (Oncovin)]] 0.05 mg/kg (maximum single dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15<br />
*High Dose [[Methotrexate (MTX)]] 400 mg/kg (20 gram maximum) IV over 4 hours on day 1<br />
*[[Folinic acid (Leucovorin)]] 10 mg/m<sup>2</sup> PO or IV every 6 hours until serum [[Methotrexate (MTX)]] levels are less than 0.1 micromolar<br />
**[[Folinic acid (Leucovorin)]] must be started 24 hours from the beginning of the [[Methotrexate (MTX)]] infusion<br />
*[[Etoposide (Vepesid)]] 2.5 mg/kg (maximum concentration of [[Etoposide (Vepesid)]] is 0.4 mg/ml) IV over 1 hour once daily on days A, B, C<br />
**Day A of chemotherapy begins when the serum [[Methotrexate (MTX)]] level is less than 0.1 micromolar<br />
**Begin [[Etoposide (Vepesid)]] infusion 1 hour before the Cyclophosphamide or CIS platin infusions<br />
*[[Cyclophosphamide (Cytoxan)]] 60 mg/kg IV once per day over 1 hour on days A, B<br />
**Day A of chemotherapy begins when the serum [[Methotrexate (MTX)]] level is less than 0.1 micromolar <br />
**Must reduce urine specific gravity to ≤ 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour<br />
*[[Mesna (Mesnex)]] 12 mg/kg IV on days A, B as described below:<br />
**Dose 1:Initial bolus dose of [[Mesna (Mesnex)]] may be administered before or at the same time as the [[Cyclophosphamide (Cytoxan)]]<br />
**Dose 2:A 3 hour infusion of [[Mesna (Mesnex)]] immediately following the [[Cyclophosphamide (Cytoxan)]] infusion <br />
**Dose 3 to 5: 3 Subsequent [[Mesna (Mesnex)]] bolus doses given at hours 6, 9, 12 or by institutional protocol<br />
**[[Mesna (Mesnex)]] 60 mg/kg/day may also be given as a 24 hour continuous infusion by institutional protocol<br />
**Day A of chemotherapy begins when the serum [[Methotrexate (MTX)]] level is less than 0.1 micromolar<br />
*[[Cisplatin (Platinol)]] 3.5 mg/kg IV infusion over 6 hours on day C<br />
**Day A of chemotherapy begins when the serum [[Methotrexate (MTX)]] level is less than 0.1 micromolar<br />
**[[Cisplatin (Platinol)]] doses may require use of mannitol to augment hydration and diuresis<br />
**Must reduce urine specific gravity to ≤ 1.010 prior to administration and maintain urine output at greater than 3 mL/kg/hour<br />
'''21 Day Course'''<br />
===Consolidation===<br />
====Chemotherapy====<br />
'''3 Cycles'''<br />
*[[Carboplatin (Paraplatin)]] 17 mg/kg IV over 2 hours given daily on Days 1 & 2<br />
** If corrected GFR is < 100 ml/min/1.73m<sup>2</sup>, the [[Carboplatin (Paraplatin)]] dose should be calculated using the modified Calvert formula<br />
<br />
*[[Thiotepa (Thioplex)]] 10 mg/kg IV over 2 hours once daily on Days 1 & 2 immediately following [[Carboplatin (Paraplatin)]] administration<br />
** Skincare, frequent bathing, and linen changes during [[Thiotepa (Thioplex)]] administration are important and required to avoid chemical skin burns<br />
<br />
*[[Filgrastim (Neupogen)]] 5 μg/kg SubQ or IV (per institutional policy) once daily starting on Day 5 (24 hours after infusion of PBSC) and continue until ANC > 2000/μL<br />
**If [[Filgrastim (Neupogen)]] is given IV, it should be administered by IV bolus over 15 to 30 minutes or by continuous infusion <br />
'''28-Day Cycle'''<br />
=====References=====<br />
#'''COG ACNS0334:''' P.D. Aridgides, G. Kang, C. Mazewski, T.E. Merchant. Outcomes after Radiation Therapy for Very Young Children with High-Risk Medulloblastoma or Supratentorial Primitive Neuroectodermal Tumor Treated on COG ACNS0334. Radiation Oncology 105, no. 1 (September 1, 2019)[https://doi.org/10.1016/j.ijrobp.2019.06.602 link to original article] NCT00336024<br />
[[Category:Medulloblastoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Pediatric neurologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Ewing_sarcoma,_pediatric&diff=55586Ewing sarcoma, pediatric2022-04-14T20:42:51Z<p>Wayneliang: changed regimen name</p>
<hr />
<div>{{#lst:Section editor transclusions|peds-sarcoma}}<br />
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|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=4}}<br />
=Upfront Therapy=<br />
==COG AEWS0031==<br />
===Regimen A Induction===<br />
*Regimen A is a standard regimen consisting of 21 day cycles<br />
====Cycles 1 & 3 (VDC)====<br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''21 day cycle'''<br />
====Cycles 2 & 4 (IE)====<br />
*[[Ifosfamide (Ifex)]] 1800 mg/m<sup>2</sup> IV infusion over 1 hour once on day 1 to 5<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once on days 1 to 5<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 1080 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Ifosfamide (Ifex)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Ifosfamide (Ifex)]] and remain until at least 8 hours after the end of the [[Ifosfamide (Ifex)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''21 day cycle'''<br />
===Regimen A Continuation===<br />
*At week 13 patients either underwent surgery, received radiation, or both<br />
*Radiation coincided with cycle 5<br />
====Cycle 5 & 9 (VDC)====<br />
Cycle 5 begins on week 15 in patients receiving surgery and on week 13 in Regimen A<sub>2</sub><br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''21 day cycle'''<br />
====Cycle 6, 8, 10, 12, & 14 (IE)====<br />
*[[Ifosfamide (Ifex)]] 1800 mg/m<sup>2</sup> IV infusion over 1 hour once on day 1 to 5<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once on days 1 to 5<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 1080 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Ifosfamide (Ifex)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Ifosfamide (Ifex)]] and remain until at least 8 hours after the end of the [[Ifosfamide (Ifex)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''21 day cycle'''<br />
====Cycle 7 (VDC) Regimen A<sub>1</sub> (Surgery Only)====<br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''21 day cycle'''<br />
====Cycle 7 (VC) Regimen A<sub>2</sub> & A<sub>3</sub> (Radiation w/ or w/o Surgery)====<br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''21 day cycle'''<br />
====Cycle 11 (VC) Regimen A<sub>1</sub> (Surgery Only)====<br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''21 day cycle'''<br />
====Cycle 11 (VDC) Regimen A<sub>2</sub> & A<sub>3</sub> (Radiation w/ or w/o Surgery)====<br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''21 day cycle'''<br />
====Cycle 13 (VC)====<br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''21 day cycle'''<br />
===Regimen B Induction===<br />
*Regimen B is a consolidated regimen consisting of 14 day cycles<br />
====Cycles 1, 3, & 5 (VDC)====<br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''14 day cycle'''<br />
====Cycle 2, 4, & 6 (IE)====<br />
*[[Ifosfamide (Ifex)]] 1800 mg/m<sup>2</sup> IV infusion over 1 hour once on day 1 to 5<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once on days 1 to 5<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 1080 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Ifosfamide (Ifex)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Ifosfamide (Ifex)]] and remain until at least 8 hours after the end of the [[Ifosfamide (Ifex)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''14 day cycle'''<br />
===Regimen B Continuation===<br />
*At week 13 patients either underwent surgery, received radiation, or both<br />
*Radiation coincided with cycle 7<br />
====Cycle 7 (VDC)====<br />
Cycle 7 begins on week 15 in patients receiving surgery and on week 13 in Regimen B<sub>2</sub><br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''14 day cycle'''<br />
<br />
<br />
====Cycle 8, 10, 12, & 14 (IE)====<br />
*[[Ifosfamide (Ifex)]] 1800 mg/m<sup>2</sup> IV infusion over 1 hour once on day 1 to 5<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV infusion over 1 to 2 hours once on days 1 to 5<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 1080 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Ifosfamide (Ifex)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Ifosfamide (Ifex)]] and remain until at least 8 hours after the end of the [[Ifosfamide (Ifex)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 6<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''14 day cycle'''<br />
====Cycle 9 (VDC) Regimen B<sub>1</sub> (Surgery Only)====<br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''14 day cycle'''<br />
====Cycle 9 (VC) Regimen B<sub>2</sub> & B<sub>3</sub> (Radiation w/ or w/o Surgery)====<br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''14 day cycle'''<br />
====Cycle 11 (VC)====<br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''14 day cycle'''<br />
====Cycle 13 (VC) Regimen B<sub>1</sub> (Surgery Only)====<br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''14 day cycle'''<br />
====Cycle 13 (VDC) Regimen B<sub>2</sub> & B<sub>3</sub> (Radiation w/ or w/o Surgery)====<br />
*[[Vincristine (Oncovin)]] 2 mg/m<sup>2</sup> IV push once on day 1 (maximum dose of 2 mg)<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated <br />
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV infusion over 48 hours once on day 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV over 1 hour on Days 1<br />
**Treat with 50% doses calculated on a m<sup>2</sup> basis for children < 1 year, then consider increasing to 75% and then to 100 % of calculated dose if tolerated<br />
*[[Mesna (Mesnex)]] 720 mg/m<sup>2</sup> IV continuous infusion on day 1<br />
**NOTE: Protocol states that [[Mesna (Mesnex)]] should be dosed as AT LEAST 60% of [[Cyclophosphamide (Cytoxan)]] m<sup>2</sup><br />
**[[Mesna (Mesnex)]] continuous infusion should be started at the same time as the [[Cyclophosphamide (Cytoxan)]] and remain until at least 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC for at least 7 days, or until ANC ≥ 750/μl, beginning on day 2<br />
**ANC ≥ 750/μl on or before day 7 of the cycle is not sufficient for discontinuing G-CSF<br />
'''14 day cycle'''<br />
===References===<br />
#'''COG AEWS0031:''' Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, and Weiss AR. Randomized Controlled Trial of Interval-Compressed Chemotherapy for the Treatment of Localized Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Nov 20;30(33):4148-4154. [https://dx.doi.org/10.1200%2FJCO.2011.41.5703 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23091096/ PubMed] NCT00006734<br />
<br />
<br />
==COG AEWS1031==<br />
===Regimen A Induction===<br />
===Regimen A Consolidation===<br />
===Regimen B Induction===<br />
===Regimen B Consolidation===<br />
[[Category:Disease-specific pages]]<br />
[[Category:Bone sarcomas]]<br />
[[Category:Pediatric solid tumors]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Classical_Hodgkin_lymphoma,_pediatric&diff=54399Classical Hodgkin lymphoma, pediatric2022-02-04T06:08:15Z<p>Wayneliang: reorganization</p>
<hr />
<div>{{#lst:Section editor transclusions|peds}}<br />
<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big><br><br><br />
''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Hodgkin_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Hodgkin lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br><br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=3}}<br />
=Guidelines=<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)]<br />
=Low Risk Pediatric Hodgkin Lymphoma=<br />
==OEPA (GPOD-HD-2002) {{#subobject:0e614f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)<br />
===Regimen {{#subobject:25c262|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.''<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Treatment group 2: [[#COPDAC|COPDAC]] x 2<br />
*Treatment group 3: [[#COPDAC|COPDAC]] x 4<br />
===References===<br />
# '''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
<br />
= Intermediate Risk Pediatric Hodgkin Lymphoma =<br />
<br />
==ABVE-PC {{#subobject:c24d93|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
===Regimen variant #1, 2 cycles with response adaptation {{#subobject:7fa6ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
'''21-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total) versus DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2; then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #2, 3 cycles with response adaptation {{#subobject:14cd95|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 3 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (5 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #3, 4 cycles with response adaptation {{#subobject:17a940|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 2<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
'''21-day cycle for 4 cycles, including the first 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders with CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Rapid early responders with less than CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===Regimen variant #4, 5 cycles {{#subobject:7e95ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old, who are slow early responders. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 3, with slow early response<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 5 cycles, including the first 3 cycles'''<br />
====Subsequent treatment====<br />
*[[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===References===<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
= High Risk Pediatric Hodgkin Lymphoma =<br />
<br />
== ABVE-PC (COG AHOD1331 Standard Arm) ==<br />
<br />
=Radiation therapy {{#subobject:b169ea|Regimen=1}}=<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy<br />
===Regimen variant #2, 21 Gy of IFRT {{#subobject:dfa48c|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2002.12.007 Nachman et al. 2002 (CCG 5942)]<br />
|1995-1998<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
|1997-2001<br />
| style="background-color:#91cf61" |Phase II<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
|2002-2009<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS48<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old.''<br />
====Preceding treatment====<br />
*CCG 5942: [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification<br />
*POG P9425: [[#ABVE-PC|ABVE-PC]] x 3 to 5<br />
*COG AHOD0031 RERs: [[#ABVE-PC|ABVE-PC]] x 4<br />
*COG AHOD0031 SERs: [[#ABVE-PC|ABVE-PC]] x 4 versus [[#ABVE-PC|ABVE-PC]] x 2, then DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2<br />
====Radiotherapy====<br />
*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.5 to 1.75 Gy per fraction<br />
===References===<br />
# '''CCG 5942:''' Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12228196 PubMed] NCT00592111<br />
## '''Update:''' Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136 PubMed]<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
[[Category:Hodgkin lymphoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Aggressive lymphomas]]<br />
[[Category:Pediatric hematologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Classical_Hodgkin_lymphoma,_pediatric&diff=54398Classical Hodgkin lymphoma, pediatric2022-02-04T05:59:49Z<p>Wayneliang: changed radiation section heading level</p>
<hr />
<div>{{#lst:Section editor transclusions|peds}}<br />
<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big><br><br><br />
''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Hodgkin_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Hodgkin lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br><br />
<br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=3}}<br />
=Guidelines=<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)]<br />
<br />
=Untreated, induction=<br />
==OEPA {{#subobject:0e614f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)<br />
<br />
===Regimen {{#subobject:25c262|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.''<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
<br />
'''28-day cycle for 2 cycles'''<br />
<br />
====Subsequent treatment====<br />
*Treatment group 2: [[#COPDAC|COPDAC]] x 2<br />
*Treatment group 3: [[#COPDAC|COPDAC]] x 4<br />
<br />
===References===<br />
# '''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
<br />
<br />
<br />
<br />
<br />
<br />
=Untreated, intermediate risk=<br />
==ABVE-PC {{#subobject:c24d93|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
===Regimen variant #1, 2 cycles with response adaptation {{#subobject:7fa6ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
<br />
'''21-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total) versus DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2; then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
<br />
===Regimen variant #2, 3 cycles with response adaptation {{#subobject:14cd95|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
<br />
'''21-day cycle for 3 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (5 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
<br />
===Regimen variant #3, 4 cycles with response adaptation {{#subobject:17a940|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 2<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
<br />
'''21-day cycle for 4 cycles, including the first 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders with CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Rapid early responders with less than CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
<br />
===Regimen variant #4, 5 cycles {{#subobject:7e95ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old, who are slow early responders. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 3, with slow early response<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 5 cycles, including the first 3 cycles'''<br />
====Subsequent treatment====<br />
*[[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===References===<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
<br />
<br />
=Radiation therapy {{#subobject:b169ea|Regimen=1}}=<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy<br />
===Regimen variant #2, 21 Gy of IFRT {{#subobject:dfa48c|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2002.12.007 Nachman et al. 2002 (CCG 5942)]<br />
|1995-1998<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
|1997-2001<br />
| style="background-color:#91cf61" |Phase II<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
|2002-2009<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS48<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old.''<br />
====Preceding treatment====<br />
*CCG 5942: [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification<br />
*POG P9425: [[#ABVE-PC|ABVE-PC]] x 3 to 5<br />
*COG AHOD0031 RERs: [[#ABVE-PC|ABVE-PC]] x 4<br />
*COG AHOD0031 SERs: [[#ABVE-PC|ABVE-PC]] x 4 versus [[#ABVE-PC|ABVE-PC]] x 2, then DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2<br />
====Radiotherapy====<br />
*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.5 to 1.75 Gy per fraction<br />
<br />
===References===<br />
# '''CCG 5942:''' Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12228196 PubMed] NCT00592111<br />
## '''Update:''' Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136 PubMed]<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
[[Category:Hodgkin lymphoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Aggressive lymphomas]]<br />
[[Category:Pediatric hematologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Classical_Hodgkin_lymphoma,_pediatric&diff=54397Classical Hodgkin lymphoma, pediatric2022-02-04T05:57:59Z<p>Wayneliang: added link to historical page</p>
<hr />
<div>{{#lst:Section editor transclusions|peds}}<br />
<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big><br><br><br />
''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Hodgkin_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Hodgkin lymphoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''<br><br />
<br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=3}}<br />
=Guidelines=<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)]<br />
<br />
=Untreated, induction=<br />
==OEPA {{#subobject:0e614f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)<br />
<br />
===Regimen {{#subobject:25c262|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.''<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
<br />
'''28-day cycle for 2 cycles'''<br />
<br />
====Subsequent treatment====<br />
*Treatment group 2: [[#COPDAC|COPDAC]] x 2<br />
*Treatment group 3: [[#COPDAC|COPDAC]] x 4<br />
<br />
===References===<br />
# '''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
<br />
<br />
<br />
<br />
<br />
<br />
=Untreated, intermediate risk=<br />
==ABVE-PC {{#subobject:c24d93|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
===Regimen variant #1, 2 cycles with response adaptation {{#subobject:7fa6ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
<br />
'''21-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total) versus DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2; then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
<br />
===Regimen variant #2, 3 cycles with response adaptation {{#subobject:14cd95|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
<br />
'''21-day cycle for 3 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (5 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
<br />
===Regimen variant #3, 4 cycles with response adaptation {{#subobject:17a940|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 2<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
<br />
'''21-day cycle for 4 cycles, including the first 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders with CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Rapid early responders with less than CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
<br />
===Regimen variant #4, 5 cycles {{#subobject:7e95ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old, who are slow early responders. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 3, with slow early response<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 5 cycles, including the first 3 cycles'''<br />
====Subsequent treatment====<br />
*[[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===References===<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
<br />
<br />
==Radiation therapy {{#subobject:b169ea|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy<br />
===Regimen variant #2, 21 Gy of IFRT {{#subobject:dfa48c|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2002.12.007 Nachman et al. 2002 (CCG 5942)]<br />
|1995-1998<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
|1997-2001<br />
| style="background-color:#91cf61" |Phase II<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
|2002-2009<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS48<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old.''<br />
====Preceding treatment====<br />
*CCG 5942: [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification<br />
*POG P9425: [[#ABVE-PC|ABVE-PC]] x 3 to 5<br />
*COG AHOD0031 RERs: [[#ABVE-PC|ABVE-PC]] x 4<br />
*COG AHOD0031 SERs: [[#ABVE-PC|ABVE-PC]] x 4 versus [[#ABVE-PC|ABVE-PC]] x 2, then DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2<br />
====Radiotherapy====<br />
*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.5 to 1.75 Gy per fraction<br />
<br />
===References===<br />
# '''CCG 5942:''' Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12228196 PubMed] NCT00592111<br />
## '''Update:''' Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136 PubMed]<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
[[Category:Hodgkin lymphoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Aggressive lymphomas]]<br />
[[Category:Pediatric hematologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Classical_Hodgkin_lymphoma,_pediatric&diff=54396Classical Hodgkin lymphoma, pediatric2022-02-04T05:55:50Z<p>Wayneliang: Moved non-current pediatric regimens to the main Hodgkin lymphoma historical page</p>
<hr />
<div>{{#lst:Section editor transclusions|peds}}<br />
<big>''This page contains studies that were specific to pediatric populations. For the more general Hodgkin lymphoma page, follow [[Hodgkin lymphoma|this link]].</big><br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=3}}<br />
=Guidelines=<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf NCCN Guidelines - Hodgkin Lymphoma (Pediatric and AYA)]<br />
<br />
=Untreated, induction=<br />
==OEPA {{#subobject:0e614f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
OEPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)<br />
<br />
===Regimen {{#subobject:25c262|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
!style="width: 33%"|Study<br />
!style="width: 33%"|Years of enrollment<br />
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.''<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Etoposide (Vepesid)]] 125 mg/m<sup>2</sup> IV once per day on days 2 to 6<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
<br />
'''28-day cycle for 2 cycles'''<br />
<br />
====Subsequent treatment====<br />
*Treatment group 2: [[#COPDAC|COPDAC]] x 2<br />
*Treatment group 3: [[#COPDAC|COPDAC]] x 4<br />
<br />
===References===<br />
# '''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
<br />
<br />
<br />
<br />
<br />
<br />
=Untreated, intermediate risk=<br />
==ABVE-PC {{#subobject:c24d93|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide<br />
===Regimen variant #1, 2 cycles with response adaptation {{#subobject:7fa6ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
<br />
'''21-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (4 cycles total) versus DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2; then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
<br />
===Regimen variant #2, 3 cycles with response adaptation {{#subobject:14cd95|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
<br />
'''21-day cycle for 3 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (5 cycles total), then [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
<br />
===Regimen variant #3, 4 cycles with response adaptation {{#subobject:17a940|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT <br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by POG P9425; Friedman et al. 2014 does not contain dosing information.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 2<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
<br />
'''21-day cycle for 4 cycles, including the first 2 cycles'''<br />
====Subsequent treatment====<br />
*Rapid early responders with CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy versus [[Hodgkin_lymphoma_-_null_regimens#Observation|no further treatment]]<br />
*Rapid early responders with less than CR: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
*Slow early responders: [[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
<br />
===Regimen variant #4, 5 cycles {{#subobject:7e95ea|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old, who are slow early responders. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''<br />
====Preceding treatment====<br />
*[[#ABVE-PC|ABVE-PC]] x 3, with slow early response<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7 <br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7<br />
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7<br />
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0<br />
====Supportive medications====<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)<br />
'''21-day cycle for 5 cycles, including the first 3 cycles'''<br />
====Subsequent treatment====<br />
*[[#Radiation_therapy_2|IFRT consolidation]] x 21 Gy<br />
===References===<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL; Children's Oncology Group. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
<br />
<br />
==Radiation therapy {{#subobject:b169ea|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy<br />
===Regimen variant #2, 21 Gy of IFRT {{#subobject:dfa48c|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2002.12.007 Nachman et al. 2002 (CCG 5942)]<br />
|1995-1998<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]<br />
|1997-2001<br />
| style="background-color:#91cf61" |Phase II<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (COG AHOD0031)]<br />
|2002-2009<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]]<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS48<br />
|-<br />
|}<br />
''This regimen is intended for pediatric patients, younger than 22 years old.''<br />
====Preceding treatment====<br />
*CCG 5942: [[#C-MOPP.2FABV|COPP-ABV hybrid]] x 4 or 6 or multi-drug therapy, depending on risk stratification<br />
*POG P9425: [[#ABVE-PC|ABVE-PC]] x 3 to 5<br />
*COG AHOD0031 RERs: [[#ABVE-PC|ABVE-PC]] x 4<br />
*COG AHOD0031 SERs: [[#ABVE-PC|ABVE-PC]] x 4 versus [[#ABVE-PC|ABVE-PC]] x 2, then DECA x 2, then [[#ABVE-PC|ABVE-PC]] x 2<br />
====Radiotherapy====<br />
*[[External beam radiotherapy]] 21 Gy in 12 to 14 fractions of 1.5 to 1.75 Gy per fraction<br />
<br />
===References===<br />
# '''CCG 5942:''' Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. [https://doi.org/10.1200/JCO.2002.12.007 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/12228196 PubMed] NCT00592111<br />
## '''Update:''' Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. [https://doi.org/10.1200/JCO.2011.41.1819 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434976/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22649136 PubMed]<br />
# '''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578<br />
# '''COG AHOD0031:''' Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk Hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. [https://doi.org/10.1200/jco.2013.52.5410 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25311218 PubMed] NCT00025259<br />
<br />
[[Category:Hodgkin lymphoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Aggressive lymphomas]]<br />
[[Category:Pediatric hematologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Classical_Hodgkin_lymphoma_-_historical&diff=54395Classical Hodgkin lymphoma - historical2022-02-04T05:55:26Z<p>Wayneliang: Moved non-current pediatric regimens to this page</p>
<hr />
<div>The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Hodgkin_lymphoma|main Hodgkin lymphoma page]] for current regimens.<br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=3}}<br />
=Untreated=<br />
==ABVDm {{#subobject:3065be|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVDm: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine, '''<u>m</u>'''ethylprednisolone<br />
===Regimen {{#subobject:c39ab4|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[http://www.bloodjournal.org/content/103/1/58.long Le Maignan et al. 2003 (H90-NM)]<br />
|1990-1996<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|EBVMm<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Dacarbazine (DTIC)]]<br />
*[[Methylprednisolone (Solumedrol)]]<br />
===References===<br />
# '''H90-NM:''' Le Maignan C, Desablens B, Delwail V, Dib M, Berthou C, Vigier M, Ghandour C, Atmani S, Casassus P, Maisonneuve H, Le Mevel A, Traulle C, Bernard M, Briere J, Colonna P, Andrieu JM. Three cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) or epirubicin, bleomycin, vinblastine, and methotrexate (EBVM) plus extended field radiation therapy in early and intermediate Hodgkin disease: 10-year results of a randomized trial. Blood. 2004 Jan 1;103(1):58-66. Epub 2003 Aug 7. [http://www.bloodjournal.org/content/103/1/58.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/12907440 PubMed] <br />
==BCVPP {{#subobject:75779b|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
BCVPP: '''<u>B</u>'''CNU (Carmustine), '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:ab3db2|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142%28197811%2942%3A5%3C2101%3A%3AAID-CNCR2820420504%3E3.0.CO%3B2-M Durant et al. 1978]<br />
|1971-1975<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[http://annals.org/aim/article-abstract/698988/bcvpp-chemotherapy-advanced-hodgkin-s-disease-evidence-greater-duration-complete Bakemeier et al. 1984]<br />
|1972-1976<br />
|style="background-color:#1a9851"|Phase III (E-esc)<br />
|[[Hodgkin_lymphoma#MOPP|MOPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<sup>1</sup><br />
|-<br />
|}<br />
''<sup>1</sup>For patients achieving CR, this regimen seemed to have comparatively superior survival.''<br />
====Chemotherapy====<br />
*[[Carmustine (BCNU)]]<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Durant JR, Gams RA, Velez-Garcia E, Bartolucci A, Wirtschafter D, Dorfman R. BCNU, velban, cyclophosphamide, procarbazine, and prednisone (BVCPP) in advanced Hodgkin's disease. Cancer. 1978 Nov;42(5):2101-10. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142%28197811%2942%3A5%3C2101%3A%3AAID-CNCR2820420504%3E3.0.CO%3B2-M link to original article] [https://pubmed.ncbi.nlm.nih.gov/719600 PubMed]<br />
# Bakemeier RF, Anderson JR, Costello W, Rosner G, Horton J, Glick JH, Hines JD, Berard CW, DeVita VT Jr; [[Study_Groups#ECOG|ECOG]]. BCVPP chemotherapy for advanced Hodgkin's disease: evidence for greater duration of complete remission, greater survival, and less toxicity than with a MOPP regimen: results of the Eastern Cooperative Oncology Group study. Ann Intern Med. 1984 Oct;101(4):447-56. [http://annals.org/aim/article-abstract/698988/bcvpp-chemotherapy-advanced-hodgkin-s-disease-evidence-greater-duration-complete link to original article] [https://pubmed.ncbi.nlm.nih.gov/6089632 PubMed]<br />
==ChlVPP/PABIOE {{#subobject:8ee324|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ChlVPP/PABIOE: '''<u>Chl</u>'''orambucil, '''<u>V</u>'''inblastine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>P</u>'''rednisolone, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide<br />
===Protocol {{#subobject:48feb0|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363648/ Hancock et al. 2001]<br />
|1992-1996<br />
| style="background-color:#1a9851" |Randomized (C)<br />
|PABIOE<br />
| style="background-color:#1a9850" |Superior OS<br />
|-<br />
|}<br />
====Chemotherapy, ChlVPP portion====<br />
*[[Chlorambucil (Leukeran)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisolone (Millipred)]]<br />
====Chemotherapy, PABIOE portion====<br />
*[[Prednisolone (Millipred)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Etoposide (Vepesid)]] <br />
===References===<br />
# Hancock BW, Gregory WM, Cullen MH, Hudson GV, Burton A, Selby P, Maclennan KA, Jack A, Bessell EM, Smith P, Linch DC; British National Lymphoma Investigation; Central Lymphoma Group. ChlVPP alternating with PABlOE is superior to PABlOE alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation/Central Lymphoma Group randomized controlled trial. Br J Cancer. 2001 May 18;84(10):1293-300. [https://www.nature.com/articles/6691778 link to orginal article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363648/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/11355937 PubMed]<br />
# '''UKLG LY09:''' Johnson PW, Radford JA, Cullen MH, Sydes MR, Walewski J, Jack AS, MacLennan KA, Stenning SP, Clawson S, Smith P, Ryder D, Hancock BW; United Kingdom Lymphoma Group. Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol. 2005 Dec 20;23(36):9208-18. Epub 2005 Nov 28. [https://doi.org/10.1200/JCO.2005.03.2151 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/16314615 PubMed] ISRCTN97144519<br />
## '''Subgroup analysis:''' Johnson PW, Sydes MR, Hancock BW, Cullen M, Radford JA, Stenning SP. Consolidation radiotherapy in patients with advanced Hodgkin's lymphoma: survival data from the UKLG LY09 randomized controlled trial (ISRCTN97144519). J Clin Oncol. 2010 Jul 10;28(20):3352-9. Epub 2010 May 24. [https://doi.org/10.1200/JCO.2009.26.0323 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20498402 PubMed]<br />
==COMP {{#subobject:8ee324|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
COMP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:48feb0|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://cancerres.aacrjournals.org/content/27/7/1258.long Moxley et al. 1967]<br />
| style="background-color:#ffffbe" |Pilot<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Methotrexate (MTX)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Moxley JH 3rd, De Vita VT, Brace K, Frei E 3rd. Intensive combination chemotherapy and X-irradiation in Hodgkin's disease. Cancer Res. 1967 Jul;27(7):1258-63. [http://cancerres.aacrjournals.org/content/27/7/1258.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/4952914 PubMed]<br />
==COPP (CCNU) {{#subobject:86879b|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
COPP: '''<u>C</u>'''CNU (Lomustine), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:cf3db2|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|rowspan=3|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract Cooper et al. 1980]<br />
|rowspan=3|1972-1975<br />
|rowspan=3 style="background-color:#1a9851"|Phase III (E-switch-ic)<br />
|1. [[#CVPP|CVPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|2. [[Hodgkin_lymphoma#MOPP|MOPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|3. [[#MVPP|MVPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Lomustine (CCNU)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/7397630 PubMed]<br />
==COPP/ABVD {{#subobject:92a2c8|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
COPP/ABVD: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine<br />
<br>C-MOPP/ABVD: '''<u>C</u>'''yclophospha'''<u>M</u>'''ide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine<br />
===Protocol variant #1, 4 cycles {{#subobject:771e81|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2002.20.2.476 Sieber et al. 2002 (GHSG HD5)]<br />
|1988-1993<br />
|style="background-color:#1a9851"|Phase III (C)<br />
|COPP/ABV/IMEP<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|[https://doi.org/10.1093/annonc/mdh046 Sieber et al. 2004 (GHSG HD6)]<br />
|1988-1993<br />
|style="background-color:#1a9851"|Phase III (C)<br />
|COPP/ABV/IMEP<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|[https://doi.org/10.1200/JCO.2003.03.023 Engert et al. 2003 (GHSG HD8)]<br />
|1993-1998<br />
|style="background-color:#91cf61"|Non-randomized portion of RCT<br />
|style="background-color:#d3d3d3"|<br />
|style="background-color:#d3d3d3"|<br />
|-<br />
|}<br />
====Chemotherapy, COPP portion====<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
'''28-day cycle for 2 total cycles of COPP, alternating with 2 total cycles of ABVD'''<br />
====Chemotherapy, ABVD portion====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Dacarbazine (DTIC)]]<br />
'''28-day cycle for 2 total cycles of ABVD, alternating with 2 total cycles of COPP'''<br />
====Subsequent treatment====<br />
*GHSG HD5 & HD6: [[Hodgkin_lymphoma#Radiation_therapy_2|EFRT]]<br />
*GHSG HD8: [[Hodgkin_lymphoma#Radiation_therapy_2|EFRT]] versus [[Hodgkin_lymphoma#Radiation_therapy_2|IFRT]]<br />
===Protocol variant #2, 6 cycles {{#subobject:6d7f98|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1093/oxfordjournals.annonc.a059357 Diehl et al. 1995 (GHSG HD3)]<br />
|style="background-color:#91cf61"|Non-randomized portion of RCT<br />
|-<br />
|}<br />
====Chemotherapy, COPP portion====<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
'''28-day cycle for 3 total cycles of COPP, alternating with 3 total cycles of ABVD'''<br />
====Chemotherapy, ABVD portion====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Dacarbazine (DTIC)]]<br />
'''28-day cycle for 3 total cycles of ABVD, alternating with 3 total cycles of COPP'''<br />
====Subsequent treatment====<br />
*COPP/ABVD x 1 (8 cycles total) versus IFRT<br />
===Protocol variant #3, 10 cycles {{#subobject:faa63|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://jjco.oxfordjournals.org/content/30/3/146.long Takenaka et al. 2000 (JCOG 8905)]<br />
|1989-1993<br />
|style="background-color:#91cf61"|Phase II<br />
|style="background-color:#d3d3d3"|<br />
|style="background-color:#d3d3d3"|<br />
|-<br />
|[https://doi.org/10.1200/jco.1998.16.12.3810 Diehl et al. 1998 (GHSG HD9)]<br />
|1993-1998<br />
|style="background-color:#1a9851"|Phase III (C)<br />
|1. [[Hodgkin_lymphoma#BEACOPP_2|BEACOPP]]<br> 2. [[Hodgkin_lymphoma#eBEACOPP_2|eBEACOPP]]<br />
|style="background-color:#fc8d59"|Seems to have inferior OS<br />
|-<br />
|[https://doi.org/10.1093/annonc/mdi023 Ballova et al. 2005 (GHSG HD9elderly)]<br />
|1993-1998<br />
|style="background-color:#1a9851"|Phase III (C)<br />
|[[Hodgkin_lymphoma#BEACOPP_2|BEACOPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy, COPP portion====<br />
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8<br />
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> (maximum dose of 150 mg) PO once per day on days 1 to 14<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 3, 8 to 10<br />
'''28-day cycle for 5 total cycles of COPP, alternating with 5 total cycles of ABVD'''<br />
====Chemotherapy, ABVD portion====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
*[[Bleomycin (Blenoxane)]] 9 mg/m<sup>2</sup> (maximum of 15 mg per dose) IV once per day on days 1 & 15 <br />
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> (maximum of 10 mg per dose) IV once per day on days 1 & 15<br />
*[[Dacarbazine (DTIC)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 5 total cycles of ABVD, alternating with 5 total cycles of COPP'''<br />
====Subsequent treatment====<br />
*Some studies: [[Hodgkin_lymphoma#Radiation_therapy_2|IFRT]] x 30 Gy after completion of chemotherapy was given to patients with bulky (at least 10 cm maximum diameter) disease<br />
====Dose modifications====<br />
*Treatment was postponed for at least 1 week or until recovery if:<br />
**Pretreatment ANC was less than 1500/uL<br />
**Platelet count was less than 100 x 10<sup>9</sup>/L<br />
**AST/S-GOT was greater than 100 IU/L<br />
**Total bilirubin was greater than 2<br />
*Vincristine and vinblastine were temporarily discontinued if patients had grade 2 or greater neurotoxicity (e.g. motor weakness, paresthesia, constipation)<br />
*Doxorubicin was discontinued if cardiac LV ejection fraction was less than 50%<br />
*Bleomycin was stopped if the PaO2 was less than 70 mmHg or if it decreased more than 10 mmHg from the previous measurement<br />
*Note: Dacarbazine 250 mg/m<sup>2</sup> was used at this dose reduction based on experiences in a pilot study in which there was severe emesis with 375 mg/m<sup>2</sup>.<br />
===References===<br />
# '''GHSG HD3:''' Diehl V, Loeffler M, Pfreundschuh M, Ruehl U, Hasenclever D, Nisters-Backes H, Sieber M, Smith K, Tesch H, Geilen W, Adler M, Bartels H, Brandenburg U, Diezler P, Doelken G, Enzian J, Fuchs R, Gassmann W, Gerhartz H, Hagenaukamp U, Hecht T, Hiller E, Hinkelbein H, Lathan B, Kirchner H, Kuehn G, Kuerten H, Loos U, Makoski B, Oertel W, Petsch S, Pfab R, Pflueger H, Planker M, Rohioff R, Sack H, Samandari S, Sauer R, Schalk K, Schmitz G, Schoppe W, Schwieder G, Szepesi S, Teichmann J, Wilhelmy W, Worst P, Fischer R, Georgii A, Huebner E, Schwarze EW; German Hodgkin's Study Group. Further chemotherapy versus low-dose involved-field radiotherapy as consolidation of complete remission after six cycles of alternating chemotherapy in patients with advance Hodgkin's disease. Ann Oncol. 1995 Nov;6(9):901-10. [https://doi.org/10.1093/oxfordjournals.annonc.a059357 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8624293 PubMed]<br />
# '''GHSG HD9:''' Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Rueffer JU, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duehmke E, Georgii A, Loeffler M. BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 1998 Dec;16(12):3810-21. [https://doi.org/10.1200/jco.1998.16.12.3810 link to original article]'''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/9850026 PubMed]<br />
## '''Update:''' Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dörken B, Müller-Hermelink HK, Dühmke E, Loeffler M; German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12;348(24):2386-95. [https://www.nejm.org/doi/full/10.1056/NEJMoa022473 link to original article]'''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/12802024 PubMed]<br />
## '''Update:''' Engert A, Diehl V, Franklin J, Lohri A, Dörken B, Ludwig WD, Koch P, Hänel M, Pfreundschuh M, Wilhelm M, Trümper L, Aulitzky WE, Bentz M, Rummel M, Sezer O, Müller-Hermelink HK, Hasenclever D, Löffler M. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009 Sep 20;27(27):4548-54. [https://doi.org/10.1200/jco.2008.19.8820 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19704068 PubMed]<br />
## '''Update:''' von Tresckow B, Kreissl S, Dipl-Math HG, Bröckelmann PJ, Pabst T, Fridrik M, Rummel M, Jung W, Thiemer J, Sasse S, Bürkle C, Baues C, Diehl V, Engert A, Borchmann P; German Hodgkin Study Group. Intensive treatment strategies in advanced-stage Hodgkin's lymphoma (HD9 and HD12): analysis of long-term survival in two randomised trials. Lancet Haematol. 2018 Oct 01;5(10):e462-73. [https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(18)30140-6/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/30290903 PubMed]<br />
# '''JCOG 8905:''' Takenaka T, Mikuni C, Miura A, Sasaki T, Suzuki H, Hotta T, Hirano M, Fukuhara S, Sugiyama H, Nasu K, Dohi H, Kozuru M, Tomonaga M, Tajima K, Niimi M, Fukuda H, Mukai K, Shimoyama M; Lymphoma Study Group of the Japan Clinical Oncology Group. Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). Jpn J Clin Oncol. 2000 Mar;30(3):146-52. [https://jjco.oxfordjournals.org/content/30/3/146.long link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/10798542 PubMed]<br />
# '''GHSG HD5:''' Sieber M, Tesch H, Pfistner B, Rueffer U, Lathan B, Brosteanu O, Paulus U, Koch T, Pfreundschuh M, Loeffler M, Engert A, Josting A, Wolf J, Hasenclever D, Franklin J, Duehmke E, Georgii A, Schalk KP, Kirchner H, Doelken G, Munker R, Koch P, Herrmann R, Greil R, Anselmo AP, Diehl V. Rapidly alternating COPP/ABV/IMEP is not superior to conventional alternating COPP/ABVD in combination with extended-field radiotherapy in intermediate-stage Hodgkin's lymphoma: final results of the German Hodgkin's Lymphoma Study Group Trial HD5. J Clin Oncol. 2002 Jan 15;20(2):476-84. [https://doi.org/10.1200/JCO.2002.20.2.476 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11786577 PubMed]<br />
# '''GHSG HD8:''' Engert A, Schiller P, Josting A, Herrmann R, Koch P, Sieber M, Boissevain F, De Wit M, Mezger J, Duhmke E, Willich N, Muller RP, Schmidt BF, Renner H, Muller-Hermelink HK, Pfistner B, Wolf J, Hasenclever D, Loffler M, Diehl V; German Hodgkin's Lymphoma Study Group. Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2003 Oct 1;21(19):3601-8. Epub 2003 Aug 11. [https://doi.org/10.1200/JCO.2003.03.023 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/12913100 PubMed]<br />
## '''Update:''' Sasse S, Klimm B, Görgen H, Fuchs M, Heyden-Honerkamp A, Lohri A, Koch O, Wilhelm M, Trenn G, Finke J, Müller RP, Diehl V, Eich HT, Borchmann P, Engert A; German Hodgkin Study Group (GHSG). Comparing long-term toxicity and efficacy of combined modality treatment including extended- or involved-field radiotherapy in early-stage Hodgkin's lymphoma. Ann Oncol. 2012 Nov;23(11):2953-9. Epub 2012 Jul 5. [https://doi.org/10.1093/annonc/mds110 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22767583 PubMed]<br />
## '''Update:''' Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, Buerkle C, Borchmann S, Fuchs M, Borchmann P, Diehl V, Engert A. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017 Jun 20;35(18):1999-2007. Epub 2017 Apr 18. [https://doi.org/10.1200/JCO.2016.70.9410 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28418763 PubMed]<br />
# '''GHSG HD6:''' Sieber M, Tesch H, Pfistner B, Rueffer U, Paulus U, Munker R, Hermann R, Doelken G, Koch P, Oertel J, Roller S, Worst P, Bischof H, Glunz A, Greil R, von Kalle K, Schalk KP, Hasenclever D, Brosteanu O, Duehmke E, Georgii A, Engert A, Loeffler M, Diehl V, Mueller RP, Willich N, Fischer R, Hansmann ML, Stein H, Schober T, Koch B; German Hodgkin's Lymphoma Study Group. Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial. Ann Oncol. 2004 Feb;15(2):276-82. [https://doi.org/10.1093/annonc/mdh046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14760122 PubMed]<br />
# '''GHSG HD9elderly:''' Ballova V, Rüffer JU, Haverkamp H, Pfistner B, Müller-Hermelink HK, Dühmke E, Worst P, Wilhelmy M, Naumann R, Hentrich M, Eich HT, Josting A, Löffler M, Diehl V, Engert A. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005 Jan;16(1):124-31. [https://doi.org/10.1093/annonc/mdi023 link to original article]'''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/15598949 PubMed]<br />
==CVPP {{#subobject:be8f99|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
CVPP: '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''inblastine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:e71c98|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|rowspan=3|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract Cooper et al. 1980]<br />
|rowspan=3|1972-1975<br />
|rowspan=3 style="background-color:#1a9851"|Phase III (E-switch-ic)<br />
|1. [[#COPP_.28CCNU.29|COPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|2. [[Hodgkin_lymphoma#MOPP|MOPP]]<br />
|style="background-color:#91cf60"|Seems to have superior CR rate<br />
|-<br />
|3. [[#MVPP|MVPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|[https://academic.oup.com/jnci/article-abstract/80/18/1466/943469 Pavlovsky et al. 1988]<br />
|1977-1986<br />
|style="background-color:#1a9851"|Randomized (E-de-esc)<br />
|CVPP & RT<br />
| style="background-color:#d73027" |Inferior FFS<sup>1</sup><br />
|-<br />
|[https://doi.org/10.1200/JCO.1997.15.7.2652 Pavlovsky et al. 1997]<br />
|1986-NR<br />
|style="background-color:#1a9851"|Randomized (C)<br />
|AOPE<br />
|style="background-color:#91cf60"|Seems to have superior CR rate<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1096-911X(199712)29:6%3C544::AID-MPO5%3E3.0.CO;2-K Sackmann-Muriel et al. 1997]<br />
|1987-1994<br />
|style="background-color:#1a9851"|Randomized (C)<br />
|AOPE<br />
|style="background-color:#91cf60"|Seems to have superior EFS<br />
|-<br />
|}<br />
''<sup>1</sup>No advantage was seen for either arm in the favorable prognosis group, whereas this arm had inferior DFS for the unfavorable prognosis group.''<br />
====Chemotherapy====<br />
*[[Lomustine (CCNU)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/7397630 PubMed]<br />
# Pavlovsky S, Maschio M, Santarelli MT, Sackmann Muriel F, Corrado C, Garcia I, Schwartz L, Montero C, Lobo Sanahuja F, Magnasco O, Raha R, Cavagnaro F. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage I-II Hodgkin's disease. J Natl Cancer Inst. 1988 Nov 16;80(18):1466-73. [https://academic.oup.com/jnci/article-abstract/80/18/1466/943469 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3184196 PubMed]<br />
## '''Update:''' Pavlovsky S, Santarelli MT, Sackmann Muriel F, Fernández I, Garcia I, Schwartz L, Montero C, Sanahuja FL, Magnasco H, Costa A, Corrado C, Raha R, Bezares R. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage III-IV A & B Hodgkin's disease. Ann Oncol. 1992 Jul;3(7):533-7. [https://doi.org/10.1093/oxfordjournals.annonc.a058255 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1498073 PubMed]<br />
# Pavlovsky S, Schvartzman E, Lastiri F, Magnasco H, Corrado C, Raslawski E, Cancela ME, Ardaiz MC, Cerutti I, Rosso A, Bruno S, Aranguren PN, Salvarezza A, Donato H, Dibar E, Zirone S; GATLA. Randomized trial of CVPP for three versus six cycles in favorable-prognosis and CVPP versus AOPE plus radiotherapy in intermediate-prognosis untreated Hodgkin's disease. J Clin Oncol. 1997 Jul;15(7):2652-8. [https://doi.org/10.1200/JCO.1997.15.7.2652 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9215837 PubMed]<br />
# Sackmann-Muriel F, Zubizarreta P, Gallo G, Scopinaro M, Alderete D, Alfaro E, Casak S, Chantada G, Felice MS, Quinteros R. Hodgkin disease in children: results of a prospective randomized trial in a single institution in Argentina. Med Pediatr Oncol. 1997 Dec;29(6):544-52. [https://onlinelibrary.wiley.com/doi/abs/10.1002/(SICI)1096-911X(199712)29:6%3C544::AID-MPO5%3E3.0.CO;2-K link to original article] [https://pubmed.ncbi.nlm.nih.gov/9324342 PubMed]<br />
==Doxorubicin & Vinblastine {{#subobject:66828f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:597e32|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2001.19.22.4238 Press et al. 2001 (SWOG S9133)]<br />
|NR-2000<br />
|style="background-color:#1a9851"|Phase III (E-esc)<br />
|STLI<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 3 cycles'''<br />
====Subsequent treatment====<br />
*STLI<br />
===References===<br />
# '''SWOG S9133:''' Press OW, LeBlanc M, Lichter AS, Grogan TM, Unger JM, Wasserman TH, Gaynor ER, Peterson BA, Miller TP, Fisher RI. Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease. J Clin Oncol. 2001 Nov 15;19(22):4238-44. [https://doi.org/10.1200/JCO.2001.19.22.4238 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/11709567 PubMed] NCT00002495<br />
==LOPP {{#subobject:f2a168|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
LOPP: '''<u>L</u>'''eukeran (Chlorambucil), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:bfcf5a|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.thegreenjournal.com/article/S0167-8140(86)80032-9/pdf Hancock 1986]<br />
|1979-NR<br />
| style="background-color:#1a9851" |Randomized (E-switch-ic)<br />
|[[Hodgkin_lymphoma#MOPP|MOPP]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[https://doi.org/10.1200/JCO.1992.10.8.1252 Hancock et al. 1992]<br />
|1983-1989<br />
| style="background-color:#1a9851" |Randomized (C)<br />
|[[#LOPP.2FEVAP|LOPP/EVAP]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Chlorambucil (Leukeran)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Hancock BW; British National Lymphoma Investigation. Randomised study of MOPP (mustine, Oncovin, procarbazine, prednisone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease. Radiother Oncol. 1986 Nov;7(3):215-21. [https://www.thegreenjournal.com/article/S0167-8140(86)80032-9/pdf link to original article] [https://pubmed.ncbi.nlm.nih.gov/3544084 PubMed]<br />
## '''Update:''' Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Haybittle JL, Bennett MH, MacLennan KA, Jelliffe AM; BNLI. British National Lymphoma Investigation randomised study of MOPP (mustine, Oncovin, procarbazine, prednisolone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease--long term results. Br J Cancer. 1991 Apr;63(4):579-82. [https://doi.org/10.1038/bjc.1991.134 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1972355/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/2021542 PubMed]<br />
# Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Bennett MH, MacLennan KA, Haybittle JL, Anderson L, Linch DC; BNLI. LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial. J Clin Oncol. 1992 Aug;10(8):1252-8. [https://doi.org/10.1200/JCO.1992.10.8.1252 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1634914 PubMed]<br />
==LOPP/EVAP {{#subobject:22b023|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
LOPP/EVAP: '''<u>L</u>'''eukeran (Chlorambucil), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>E</u>'''toposide, '''<u>V</u>'''inblastine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''rednisone<br />
===Protocol {{#subobject:53f4da|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.1992.10.8.1252 Hancock et al. 1992]<br />
|1983-1989<br />
| style="background-color:#1a9851" |Randomized (E-switch-ic)<br />
|[[#LOPP|LOPP]]<br />
| style="background-color:#91cf60" |Seems to have superior OS<br />
|-<br />
|[https://doi.org/10.1093/annonc/5.suppl_2.s117 Hancock et al. 1994]<br />
|1990-1991<br />
| style="background-color:#1a9851" |Randomized (C)<br />
|LOPP-EVA<br />
| style="background-color:#1a9850" |Superior CR rate<br />
|-<br />
|}<br />
====Chemotherapy, LOPP portion====<br />
*[[Chlorambucil (Leukeran)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
====Chemotherapy, EVAP portion====<br />
*[[Etoposide (Vepesid)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Bennett MH, MacLennan KA, Haybittle JL, Anderson L, Linch DC; BNLI. LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial. J Clin Oncol. 1992 Aug;10(8):1252-8. [https://doi.org/10.1200/JCO.1992.10.8.1252 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1634914 PubMed]<br />
# Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Linch DC, Anderson L, MacLennan KA; BNLI. Hybrid LOPP/EVA is not better than LOPP alternating with EVAP: a prematurely terminated British National Lymphoma Investigation randomized trial. Ann Oncol. 1994;5 Suppl 2:117-20. [https://doi.org/10.1093/annonc/5.suppl_2.s117 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8204511 PubMed]<br />
==Mechlorethamine monotherapy {{#subobject:3674c2|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:2761c1|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://jamanetwork.com/journals/jama/fullarticle/288442 Goodman et al. 1946]<br />
|NR<br />
| style="background-color:#91cf61" |Non-randomized<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://jamanetwork.com/journals/jama/article-abstract/288767 Jacobson et al. 1946]<br />
|1943-1945<br />
| style="background-color:#91cf61" |Non-randomized<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[http://annals.org/aim/article/673669/nitrogen-mustard-therapeutic-agent-hodgkin-s-disease-lymphosarcoma-leukemia Wintrobe et al. 1947]<br />
|NR<br />
| style="background-color:#91cf61" |Non-randomized<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[http://annals.org/aim/article/673986/use-nitrogen-mustard-hodgkin-s-disease-lymphosarcoma Meyer & Overmiller 1949]<br />
|1946-1947<br />
| style="background-color:#91cf61" |Non-randomized<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://jamanetwork.com/journals/jama/article-abstract/337835 Jacobs et al. 1968]<br />
|1960-1963<br />
| style="background-color:#1a9851" |Randomized (C)<br />
|Cyclophosphamide<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
''These references are of major historic interest as they are the first systemic chemotherapy trials in humans. Note that some of these early trials used nitrogen mustards other than mechlorethamine but are grouped here for simplicity.''<br />
====Chemotherapy====<br />
*[[Mechlorethamine (Mustargen)]]<br />
===References===<br />
# Goodman LS, Wintrobe MM, Dameshek W, Goodman MJ, Gilman A, McLennan MT. Nitrogen mustard therapy; use of methyl-bis (beta-chloroethyl) amine hydrochloride and tris (beta-chloroethyl) amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. J Am Med Assoc. 1946 Sep 21;132:126-32. [https://jamanetwork.com/journals/jama/fullarticle/288442 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20997191 PubMed]<br />
# Jacobson LO, Spurr CL, Guzman-Barron ES, Smith T, Lushbaugh C, Dick GF. Nitrogen mustard therapy; studies on the effect of methyl-bis (beta-chloroethyl) amine hydrochloride on neoplastic diseases and allied disorders of the hemopoietic system. J Am Med Assoc. 1946 Oct 5;132:263-71. [https://jamanetwork.com/journals/jama/article-abstract/288767 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20997209 PubMed]<br />
# Wintrobe MM, Huguley CM Jr, McLennan MT, Penna de Carvalho Lima L. Nitrogen mustard as a therapeutic agent for Hodgkin's disease, lymphosarcoma and leukemia. Ann Intern Med. 1947 Oct;27(4):529-40. [http://annals.org/aim/article/673669/nitrogen-mustard-therapeutic-agent-hodgkin-s-disease-lymphosarcoma-leukemia link to original article] [https://pubmed.ncbi.nlm.nih.gov/20268426 PubMed]<br />
# Meyer AH, Overmiller WC. The use of nitrogen mustard in Hodgkin's disease and lymphosarcoma. Ann Intern Med. 1949 Feb;30(2):381-6. [http://annals.org/aim/article/673986/use-nitrogen-mustard-hodgkin-s-disease-lymphosarcoma link to original article] [https://pubmed.ncbi.nlm.nih.gov/18109292 PubMed]<br />
# Jacobs EM, Peters FC, Luce JK, Zippin C, Wood DA. Mechlorethamine HCl and cyclophosphamide in the treatment of Hodgkin's disease and the lymphomas. JAMA. 1968 Feb 5;203(6):392-8. [https://jamanetwork.com/journals/jama/article-abstract/337835 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4865234 PubMed]<br />
==MOPP/ABVD {{#subobject:f28468|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
MOPP/ABVD: '''<u>M</u>'''ustargen (Mechlorethamine), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine<br />
===Protocol {{#subobject:5b28f5|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.nejm.org/doi/full/10.1056/NEJM198204013061303 Santoro et al. 1982]<br />
|1974-1980<br />
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)<br />
|[[Hodgkin_lymphoma#MOPP|MOPP]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|[https://doi.org/10.1200/jco.1994.12.2.279 Somers et al. 1994]<br />
|1981-1986<br />
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)<br />
|[[Hodgkin_lymphoma#MOPP|MOPP]]<br />
| style="background-color:#91cf60" |Seems to have superior FFS<br />
|-<br />
| rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJM199211193272102 Canellos et al. 1992 (CALGB 8251)]<br />
|rowspan=2|1982-NR<br />
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)<br />
|1. [[Hodgkin_lymphoma#ABVD_3|ABVD]]<br />
| style="background-color:#ffffbf" |Seems not superior<sup>1</sup><br />
|-<br />
|2. [[Hodgkin_lymphoma#MOPP|MOPP]]<br />
| style="background-color:#91cf60" |Seems to have superior EFS<sup>1</sup><br />
|-<br />
|[https://doi.org/10.1200/jco.1996.14.5.1421 Viviani et al. 1996]<br />
|1982-1990<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|MOPP-ABVD<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[https://doi.org/10.1200/jco.1997.15.4.1638 Connor et al. 1997 (NCIC-CTG HD4)]<br />
|1984-1989<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma#MOPP-ABV_3|MOPP-ABV]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[https://doi.org/10.1200/JCO.1998.16.3.897 Hutchinson et al. 1998 (CCG-521)]<br />
|1986-1990<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|[[Hodgkin_lymphoma#ABVD_3|ABVD]], then RT<br />
| style="background-color:#fee08b" |Might have inferior EFS<br />
|-<br />
|}<br />
''<sup>1</sup>Reported efficacy for CALGB 8251 is based on the 2009 update.''<br />
====Chemotherapy, MOPP portion====<br />
*[[Mechlorethamine (Mustargen)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
====Chemotherapy, ABVD portion====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Dacarbazine (DTIC)]]<br />
===References===<br />
# Santoro A, Bonadonna G, Bonfante V, Valagussa P. Alternating drug combinations in the treatment of advanced Hodgkin's disease. N Engl J Med. 1982 Apr 1;306(13):770-5. [https://www.nejm.org/doi/full/10.1056/NEJM198204013061303 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6174865 PubMed]<br />
## '''Update:''' Bonadonna G, Valagussa P, Santoro A. Alternating non-cross-resistant combination chemotherapy or MOPP in stage IV Hodgkin's disease: a report of 8-year results. Ann Intern Med. 1986 Jun;104(6):739-46. [http://annals.org/article.aspx?articleid=700485 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2422994 PubMed]<br />
# '''CALGB 8251:''' Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992 Nov 19;327(21):1478-84. [https://www.nejm.org/doi/10.1056/NEJM199211193272102 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1383821 PubMed]<br />
## '''Update:''' Canellos GP, Niedzwiecki D. Long-term follow-up of Hodgkin's disease trial. N Engl J Med. 2002 May 2;346(18):1417-8. [https://www.nejm.org/doi/10.1056/NEJM200205023461821 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11986425 PubMed]<br />
## '''Update:''' Canellos GP, Niedzwiecki D, Johnson JL. Long-term follow-up of survival in Hodgkin's lymphoma. N Engl J Med. 2009 Dec 10;361(24):2390-1. [https://www.nejm.org/doi/10.1056/NEJMc0906731 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20007568 PubMed]<br />
# Somers R, Carde P, Henry-Amar M, Tarayre M, Thomas J, Hagenbeek A, Monconduit M, de Pauw BE, Breed WP, Verdonck L, Burgers JMV, Eghbali H, Zittoun R; [[Study_Groups#EORTC|EORTC]]. A randomized study in stage IIIB and IV Hodgkin's disease comparing eight courses of MOPP versus an alteration of MOPP with ABVD: a European Organisation for Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie controlled clinical trial. J Clin Oncol. 1994 Feb;12(2):279-87. [https://doi.org/10.1200/jco.1994.12.2.279 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7509381 PubMed]<br />
# Viviani S, Bonadonna G, Santoro A, Bonfante V, Zanini M, Devizzi L, Soncini F, Valagussa P. Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin's disease: ten-year results. J Clin Oncol. 1996 May;14(5):1421-30. [https://doi.org/10.1200/jco.1996.14.5.1421 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8622055 PubMed]<br />
# '''NCIC-CTG HD4:''' Connors JM, Klimo P, Adams G, Burns BF, Cooper I, Meyer RM, O'Reilly SE, Pater J, Quirt I, Sadura A, Shustik C, Skillings J, Sutcliffe S, Verma S, Yoshida S, Zee B. Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group. J Clin Oncol. 1997 Apr;15(4):1638-45. Erratum in: J Clin Oncol 1997 Jul;15(7):2762. [https://doi.org/10.1200/jco.1997.15.4.1638 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9193364 PubMed]<br />
# '''CCG-521:''' Hutchinson RJ, Fryer CJ, Davis PC, Nachman J, Krailo MD, O'Brien RT, Collins RD, Whalen T, Reardon D, Trigg ME, Gilchrist GS. MOPP or radiation in addition to ABVD in the treatment of pathologically staged advanced Hodgkin's disease in children: results of the Children's Cancer Group Phase III Trial. J Clin Oncol. 1998 Mar;16(3):897-906. [https://doi.org/10.1200/JCO.1998.16.3.897 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9508171 PubMed]<br />
==MVPP {{#subobject:b01f3a|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
MVPP: '''<u>M</u>'''echlorethamine, '''<u>V</u>'''inblastine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:312fd8|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|rowspan=3|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract Cooper et al. 1980]<br />
|rowspan=3|1972-1975<br />
|rowspan=3 style="background-color:#1a9851"|Phase III (E-switch-ic)<br />
|1. [[#COPP_.28CCNU.29|COPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|2. [[#CVPP|CVPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|3. [[Hodgkin_lymphoma#MOPP|MOPP]]<br />
|style="background-color:#ffffbf"|Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Mechlorethamine (Mustargen)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/7397630 PubMed]<br />
==NOVP {{#subobject:230457|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
NOVP: '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>O</u>'''ncovin (Vincristine), '''<u>V</u>'''inblastine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:5bf81f|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://pubmed.ncbi.nlm.nih.gov/2259922 Hagemeister et al. 1990]<br />
|style="background-color:#91cf61"|Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Mitoxantrone (Novantrone)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
# Hagemeister FB, Cabanillas F, Velásquez WS, Meistrich ML, Liang JC, McLaughlin P, Redman JR, Romaguera JE, Rodríguez MA, Swan F Jr, Fuller LM. NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease. Semin Oncol. 1990 Dec;17(6 Suppl 10):34-8. [http://www.seminoncol.org/article/0093-7754(90)90122-J/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/2259922 PubMed]<br />
==SCAB {{#subobject:344883|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
SCAB: '''<u>S</u>'''treptozocin, '''<u>C</u>'''CNU (Lomustine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin<br />
===Regimen {{#subobject:a68d3b|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19810115)47:2%3C224::AID-CNCR2820470203%3E3.0.CO;2-6/abstract Diggs et al. 1981]<br />
|style="background-color:#91cf61"|Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Streptozocin (Zanosar)]]<br />
*[[Lomustine (CCNU)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
===References===<br />
# Diggs CH, Wiernik PH, Sutherland JC. Treatment of advanced untreated Hodgkin's disease with SCAB--an alternative to MOPP. Cancer. 1981 Jan 15;47(2):224-8. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19810115)47:2%3C224::AID-CNCR2820470203%3E3.0.CO;2-6/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/6161689 PubMed]<br />
## '''Update:''' Wiernik PH, Schiffer CA. Long-term follow-up of advanced Hodgkin's disease patients treated with a combination of streptozotocin, lomustine (CCNU), doxorubicin and bleomycin (SCAB). J Cancer Res Clin Oncol. 1988;114(1):105-7. [https://doi.org/10.1007/bf00390494 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2450876 PubMed]<br />
==Vinblastine monotherapy {{#subobject:b1c2da|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:48bfd8|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://jamanetwork.com/journals/jama/article-abstract/657749 Stutzman et al. 1966]<br />
|1963-1964<br />
|style="background-color:#1a9851"|Randomized (E-switch-ic)<br />
|Cyclophosphamide<br />
| style="background-color:#1a9850" |Superior ORR<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Vinblastine (Velban)]]<br />
===References===<br />
# Stutzman L, Ezdinli EZ, Stutzman MA. Vinblastine sulfate vs cyclophosphamide in the therapy for lymphoma. JAMA. 1966 Jan 17;195(3):173-8. [https://jamanetwork.com/journals/jama/article-abstract/657749 link to original article] [https://pubmed.ncbi.nlm.nih.gov/5322863 PubMed]<br />
==OPPA {{#subobject:6418c0|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
OPPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)<br />
===Regimen {{#subobject:e17569|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" | Phase II<br />
|-<br />
|}<br />
''This regimen is meant for girls. Patients with early-stage disease only received the OPPA portion, see text for details.''<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
'''28-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*Treatment group 2: [[#C-MOPP|COPP]] x 2<br />
*Treatment group 3: [[#C-MOPP|COPP]] x 4<br />
===References===<br />
#'''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
==VAMP (Methotrexate) {{#subobject:4d666a|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VAMP: '''<u>V</u>'''inblastine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethrotrexate, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:6f694d|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526806/ Metzger et al. 2012 (HOD99)]<br />
| style="background-color:#91cf61" |Phase 2<br />
|-<br />
|}<br />
''To be completed? This is to be distinguished from the VAMP protocols used in AML and multiple myeloma.''<br />
====Chemotherapy====<br />
*[[Vinblastine (Velban)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Methotrexate (MTX)]]<br />
*[[Prednisone (Sterapred)]]<br />
'''4 cycles'''<br />
====Subsequent treatment====<br />
*Early responders: [[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]] versus [[#Radiation_therapy_2|RT]]<br />
===References===<br />
#'''HOD99:''' Metzger ML, Weinstein HJ, Hudson MM, Billett AL, Larsen EC, Friedmann A, Howard SC, Donaldson SS, Krasin MJ, Kun LE, Marcus KJ, Yock TI, Tarbell N, Billups CA, Wu J, Link MP. Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma. JAMA. 2012 Jun 27;307(24):2609-16. [https://jamanetwork.com/journals/jama/fullarticle/1199151 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526806/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22735430 PubMed]<br />
==ABVE {{#subobject:c24h71|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVE: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide<br />
===Regimen {{#subobject:7fa7ya|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3468662/ Tebbi et al. 2012 (POG P9426)]<br />
|1996-2001<br />
| style="background-color:#91cf61" |Non-randomized (see note)<br />
|-<br />
|}<br />
''Note: this trial had a randomization to receive or not receive dexrazoxane. Labeled here as non-randomized because this drug does not have antineoplastic properties.''<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15<br />
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV once per day on days 1 & 15<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 15<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5<br />
====Supportive medications====<br />
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 6 to 14, then once per day on days 16 until ANC greater than 1000/uL<br />
'''28-day cycle for 2 cycles'''<br />
====Subsequent treatment====<br />
*CR: [[#Radiation_therapy_2|IFRT consolidation]]<br />
*Other than CR: [[#ABVE|ABVE]] x 2, then [[#Radiation_therapy_2|IFRT consolidation]]<br />
===References===<br />
#'''POG P9426:''' Tebbi CK, Mendenhall NP, London WB, Williams JL, Hutchison RE, Fitzgerald TJ, de Alarcón PA, Schwartz C, Chauvenet A. Response-dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2012 Dec 15;59(7):1259-65. Epub 2012 Aug 21. [https://doi.org/10.1002/pbc.24279 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3468662/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/22911615/ PubMed] NCT00002827<br />
==MOPP {{#subobject:bcde0|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
MOPP: '''<u>M</u>'''echlorethamine, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen variant #3, uncapped vincristine {{#subobject:ff7478|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[http://www.bloodjournal.org/content/42/2/163.long Young et al. 1973a]<br />
|1964-NR<br />
| style="background-color:#91cf61" |Non-randomized (RT)<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197610)38:4%3C1494::AID-CNCR2820380408%3E3.0.CO;2-E Kolygin 1976]<br />
|1970-1975<br />
| style="background-color:#91cf61" |Non-randomized (RT)<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|}<br />
==== Chemotherapy====<br />
*[[Mechlorethamine (Mustargen)]] 6 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 14<br />
'''28-day cycle for 6 to 8 cycles'''<br />
===References===<br />
#Young RC, DeVita VT, Johnson RE. Hodgkin's disease in childhood. Blood. 1973 Aug;42(2):163-74. [http://www.bloodjournal.org/content/42/2/163.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/4793108 PubMed]<br />
#Kolygin BA. Combination chemotherapy of Hodgkin's disease in children. Cancer. 1976 Oct;38(4):1494-7. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(197610)38:4%3C1494::AID-CNCR2820380408%3E3.0.CO;2-E link to original article] [https://pubmed.ncbi.nlm.nih.gov/991072 PubMed]<br />
<br />
<br />
=Consolidation after upfront therapy=<br />
==C-MOPP {{#subobject:034931|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
C-MOPP: '''<u>C</u>'''yclophospha'''<u>M</u>'''ide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
<br>COPP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen variant #1, 2 cycles {{#subobject:cfcc4b|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Preceding treatment====<br />
*[[#OPPA|OPPA]] x 2<br />
====Chemotherapy====<br />
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
'''28-day cycle for 2 cycles'''<br />
===Regimen variant #2, 4 cycles {{#subobject:228db9|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Preceding treatment====<br />
*[[#OPPA|OPPA]] x 2<br />
====Chemotherapy====<br />
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
'''28-day cycle for 4 cycles'''<br />
===References===<br />
#'''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
==COPDAC {{#subobject:195ad7|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
COPDAC: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>DAC</u>'''arbazine<br />
===Regimen variant #1, 2 cycles {{#subobject:e9d06d|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Preceding treatment====<br />
*[[#OEPA|OEPA]] x 2<br />
====Chemotherapy====<br />
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Dacarbazine (DTIC)]] 250 mg/m<sup>2</sup> IV once per day on days 1 to 4<br />
'''28-day cycle for 2 cycles'''<br />
===Regimen variant #2, 4 cycles {{#subobject:515d30|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;"<br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]<br />
|2002-2005<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Preceding treatment====<br />
*[[#OEPA|OEPA]] x 2<br />
==== Chemotherapy====<br />
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15<br />
*[[Dacarbazine (DTIC)]] 250 mg/m<sup>2</sup> IV once per day on days 1 to 4<br />
'''28-day cycle for 4 cycles'''<br />
===References ===<br />
#'''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832<br />
<br />
<br />
=Maintenance after upfront therapy=<br />
==Bacillus Calmette-Guérin (BCG) monotherapy {{#subobject:e1fd72|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:52ca75|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.nejm.org/doi/full/10.1056/NEJM197412052912305 Sokal et al. 1974]<br />
|1965-1967<br />
| style="background-color:#91cf61" |Randomized, <20 pts in this subgroup (E-esc)<br />
|[[Hodgkin_lymphoma_-_null_regimens#Observation_2|Observation]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
''Note: this study was open to patients with "malignant lymphoma" but the majority had Hodgkin disease.''<br />
==== Immunotherapy====<br />
*[[Bacillus Calmette-Guérin (BCG)]]<br />
===References===<br />
#Sokal JE, Aungst CW, Snyderman M. Delay in progression of malignant lymphoma after BCG vaccination. N Engl J Med. 1974 Dec 5;291(23):1226-30. [https://www.nejm.org/doi/full/10.1056/NEJM197412052912305 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4609380 PubMed]<br />
=Relapsed or refractory, salvage therapy =<br />
==ABDIC {{#subobject:c5c5ab|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABDIC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>DI</u>'''C (Dacarbazine), '''<u>C</u>'''CNU (Lomustine), Prednisone<br />
===Regimen {{#subobject:4ba1e1|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19801201)46:11%3C2349::AID-CNCR2820461105%3E3.0.CO;2-V/abstract Rodgers et al. 1980]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Dacarbazine (DTIC)]]<br />
*[[Lomustine (CCNU)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
#Rodgers RW, Gamble JF, Loh KK, Shullenberger CC. Adriamycin, bleomycin, DIC, CCNU, and prednisone (ABDIC) chemotherapy in MOPP-resistant Hodgkin's disease. Cancer. 1980 Dec 1;46(11):2349-55. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19801201)46:11%3C2349::AID-CNCR2820461105%3E3.0.CO;2-V/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/6159961 PubMed]<br />
##'''Update:''' Tannir N, Hagemeister F, Velasquez W, Cabanillas F. Long-term follow-up with ABDIC salvage chemotherapy of MOPP-resistant Hodgkin's disease. J Clin Oncol. 1983 Jul;1(7):432-9. [https://doi.org/10.1200/jco.1983.1.7.432 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6199478 PubMed]<br />
==ABVD {{#subobject:c5a35d|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
ABVD: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine<br />
===Regimen {{#subobject:ae32ee|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" | Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197806)41:6%3C2107::AID-CNCR2820410606%3E3.0.CO;2-L/abstract Krikorian et al. 1978]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|[https://doi.org/10.1007/bf00254081 Santoro & Bonadonna 1979]<br />
| style="background-color:#91cf61" | Non-randomized<br />
|-<br />
|[http://annals.org/article.aspx?articleid=695320 Santoro et al. 1982a]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|[http://annals.org/article.aspx?articleid=698987 Harker et al. 1984]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
''This is for historical interest only; ABVD is no longer used in the salvage setting.''<br />
====Chemotherapy ====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Dacarbazine (DTIC)]]<br />
===References===<br />
#Krikorian JG, Portlock CS, Rosenberg SA. Treatment of advanced Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) after failure of MOPP therapy. Cancer. 1978 Jun;41(6):2107-11. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197806)41:6%3C2107::AID-CNCR2820410606%3E3.0.CO;2-L/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/77716 PubMed]<br />
#Santoro A, Bonadonna G. Prolonged disease-free survival in MOPP-resistant Hodgkin's disease after treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). Cancer Chemother Pharmacol. 1979;2(2):101-5. [https://doi.org/10.1007/bf00254081 link to original article] [https://pubmed.ncbi.nlm.nih.gov/93984 PubMed]<br />
#Santoro A, Bonfante V, Bonadonna G. Salvage chemotherapy with ABVD in MOPP-resistant Hodgkin's disease. Ann Intern Med. 1982 Feb;96(2):139-43. [http://annals.org/article.aspx?articleid=695320 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6174060 PubMed]<br />
#Harker WG, Kushlan P, Rosenberg SA. Combination chemotherapy for advanced Hodgkin's disease after failure of MOPP: ABVD and B-CAVe. Ann Intern Med. 1984 Oct;101(4):440-6. [http://annals.org/article.aspx?articleid=698987 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6206757 PubMed]<br />
==B-CAVe {{#subobject:41a31c|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
B-CAVe: '''<u>B</u>'''leomycin, '''<u>C</u>'''CNU (Lomustine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''inblastin'''<u>e</u>'''<br />
===Regimen {{#subobject:c53f0c|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197805)41:5%3C1670::AID-CNCR2820410504%3E3.0.CO;2-Y/abstract Porzig et al. 1978]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|[http://annals.org/article.aspx?articleid=698987 Harker et al. 1984]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Lomustine (CCNU)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Vinblastine (Velban)]]<br />
===References===<br />
#Porzig KJ, Portlock CS, Robertson A, Rosenberg SA. Treatment of advanced Hodgkin's disease with B-CAVE following MOPP failure. Cancer. 1978 May;41(5):1670-5. [https://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197805)41:5%3C1670::AID-CNCR2820410504%3E3.0.CO;2-Y/abstract link to original article] [https://pubmed.ncbi.nlm.nih.gov/77180 PubMed]<br />
#Harker WG, Kushlan P, Rosenberg SA. Combination chemotherapy for advanced Hodgkin's disease after failure of MOPP: ABVD and B-CAVe. Ann Intern Med. 1984 Oct;101(4):440-6. [http://annals.org/article.aspx?articleid=698987 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6206757 PubMed]<br />
==BVCPP {{#subobject:cb42cf|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
BVCPP: '''<u>B</u>'''CNU (Carmustine), '''<u>V</u>'''inblastine, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:514e7d|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142%28197811%2942%3A5%3C2101%3A%3AAID-CNCR2820420504%3E3.0.CO%3B2-M Durant et al. 1978]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Carmustine (BCNU)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
====Subsequent treatment====<br />
*Patients who achieved CR: No additional therapy versus [[Hodgkin_lymphoma#MOPP|MOPP]] x 6 versus BVCPP x 6 additional cycles<br />
===References===<br />
#Durant JR, Gams RA, Velez-Garcia E, Bartolucci A, Wirtschafter D, Dorfman R. BCNU, velban, cyclophosphamide, procarbazine, and prednisone (BVCPP) in advanced Hodgkin's disease. Cancer. 1978 Nov;42(5):2101-10. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142%28197811%2942%3A5%3C2101%3A%3AAID-CNCR2820420504%3E3.0.CO%3B2-M link to original article] [https://pubmed.ncbi.nlm.nih.gov/719600 PubMed]<br />
==BVDS {{#subobject:3a24f9|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
BVDS: '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''oxorubicin, '''<u>S</u>'''treptozocin<br />
===Regimen {{#subobject:41d09e|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://jamanetwork.com/journals/jama/article-abstract/350618 Vinciguerra et al. 1977]<br />
| style="background-color:#ffffbe" |Non-randomized, <20 pts<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Bleomycin (Blenoxane)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Streptozocin (Zanosar)]]<br />
===References===<br />
#Vinciguerra V, Coleman M, Jarowski CI, Degnan TJ, Silver RT. A new combination chemotherapy for resistant Hodgkin disease. JAMA. 1977 Jan 3;237(1):33-5. [https://jamanetwork.com/journals/jama/article-abstract/350618 link to original article] [https://pubmed.ncbi.nlm.nih.gov/62854 PubMed]<br />
==CEP {{#subobject:a1a2cc|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
CEP: '''<u>C</u>'''CNU (Lomustine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednimustine<br />
===Regimen {{#subobject:a353e9|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://pubmed.ncbi.nlm.nih.gov/2420012 Santoro et al. 1986]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Lomustine (CCNU)]]<br />
*[[Etoposide (Vepesid)]]<br />
*[[Prednimustine (Stereocyt)]]<br />
===References===<br />
#Santoro A, Viviani S, Valagussa P, Bonfante V, Bonadonna G. CCNU, etoposide, and prednimustine (CEP) in refractory Hodgkin's disease. Semin Oncol. 1986 Mar;13(1 Suppl 1):23-6. [https://pubmed.ncbi.nlm.nih.gov/2420012 PubMed]<br />
==CVB {{#subobject:b2b2cc|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
CVB: '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''inblastine, '''<u>B</u>'''leomycin<br />
===Regimen {{#subobject:a464e9|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(75)92069-3/fulltext Goldman & Dawson 1975]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Lomustine (CCNU)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
===References===<br />
#Goldman JM, Dawson AA. Combination therapy for advanced resistant Hodgkin's disease. Lancet. 1975 Dec 20;2(7947):1224-7. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(75)92069-3/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/53720 PubMed]<br />
==CVPP {{#subobject:be8f99|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
CVPP: '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''inblastine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:f32d98|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.1986.4.6.838 Vinciguerra et al. 1986]<br />
|1975-1981<br />
| style="background-color:#1a9851" |Randomized (C)<br />
|1. ABOS<br> 2. CVPP/ABOS<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Lomustine (CCNU)]]<br />
*[[Vinblastine (Velban)]]<br />
*[[Procarbazine (Matulane)]]<br />
*[[Prednisone (Sterapred)]]<br />
===References===<br />
#Vinciguerra V, Propert KJ, Coleman M, Anderson JR, Stutzman L, Pajak TF, Nissen NI, Frizzera G, Gottlieb A, Holland JF; [[Study_Groups#CALGB|CALGB]]. Alternating cycles of combination chemotherapy for patients with recurrent Hodgkin's disease following radiotherapy: a prospectively randomized study by the Cancer and Leukemia Group B. J Clin Oncol. 1986 Jun;4(6):838-46. [https://doi.org/10.1200/JCO.1986.4.6.838 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2423652 PubMed]<br />
==SCAB {{#subobject:04355f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
SCAB: '''<u>S</u>'''treptozocin, '''<u>C</u>'''CNU (Lomustine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin<br />
===Regimen {{#subobject:5c34db|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1002/mpo.2950030106 Levi et al. 1977]<br />
| style="background-color:#ffffbe" |Non-randomized, <20 pts<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Streptozocin (Zanosar)]]<br />
*[[Lomustine (CCNU)]]<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Bleomycin (Blenoxane)]]<br />
===References===<br />
#Levi JA, Wiernik PH, Diggs CH. Combination chemotherapy of advanced previously treated Hodgkin's disease with streptozotocin, CCNU, adriamycin and bleomycin. Med Pediatr Oncol. 1977;3(1):33-40. [https://doi.org/10.1002/mpo.2950030106 link to original article] [https://pubmed.ncbi.nlm.nih.gov/65727 PubMed]<br />
=Relapsed or refractory, further lines of therapy=<br />
==Carmustine monotherapy {{#subobject:f072cf|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:d61e28|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.nejm.org/doi/full/10.1056/NEJM197108262850902 Young et al. 1971]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Carmustine (BCNU)]]<br />
===References===<br />
#Young RC, DeVita VT Jr, Serpick AA, Canellos GP. Treatment of advanced Hodgkin's disease with (1,3 bis (2-chloroethyl)-1-nitrosourea) BCNU. N Engl J Med. 1971 Aug 26;285(9):475-9. [https://www.nejm.org/doi/full/10.1056/NEJM197108262850902 link to original article] [https://pubmed.ncbi.nlm.nih.gov/5558887 PubMed]<br />
==Doxorubicin & Lomustine {{#subobject:7e7049|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:e9f038|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://jamanetwork.com/journals/jama/article-abstract/355977 Williams & Einhorn 1977]<br />
| style="background-color:#ffffbe" |Non-randomized, <20 pts<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]]<br />
*[[Lomustine (CCNU)]]<br />
===References===<br />
#Williams SD, Einhorn LH. Combination chemotherapy with doxorubicin and lomustine: treatment of refractory Hodgkin's disease. JAMA. 1977 Oct 10;238(15):1659-61. [https://jamanetwork.com/journals/jama/article-abstract/355977 link to original article] [https://pubmed.ncbi.nlm.nih.gov/578254 PubMed]<br />
==Sirolimus & Vorinostat {{#subobject:273a59|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:91d698|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1158/1078-0432.ccr-20-1215 Janku et al. 2020 (MDACC 2009-0729)]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
''This is a very heavily pre-treated cohort, median of 6 prior therapies; doses here are one level below MTD and are proposed as the ongoing doses to be studied.''<br />
====Targeted therapy====<br />
*[[Sirolimus (Rapamune)]] 4 mg PO once per day<br />
*[[Vorinostat (Zolinza)]] as follows:<br />
**Cycle 1: 300 mg PO once per day on days 7 to 28<br />
**Subsequent cycles: 300 mg PO once per day on days 1 to 28<br />
'''28-day cycles'''<br />
===References===<br />
<br />
#'''MDACC 2009-0729:''' Janku F, Park H, Call SG, Madwani K, Oki Y, Subbiah V, Hong DS, Naing A, Velez-Bravo VM, Barnes TG, Hagemeister FB, Falchook GS, Karp DD, Wheler JJ, Piha-Paul SA, Garrido-Laguna I, Shpall EJ, Fayad LE, Neelapu SS, Meric-Bernstam F, Kurzrock R, Fanale MA. Safety and Efficacy of Vorinostat Plus Sirolimus or Everolimus in Patients with Relapsed Refractory Hodgkin Lymphoma. Clin Cancer Res. 2020 Nov 1;26(21):5579-5587. Epub 2020 Oct 14. [https://doi.org/10.1158/1078-0432.ccr-20-1215 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33055173/ PubMed] NCT01087554<br />
[[Category:Hodgkin lymphoma regimens]]<br />
[[Category:Historical regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Aggressive lymphomas]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Pediatric_Lomustine_Dosing_Chart&diff=54394Pediatric Lomustine Dosing Chart2022-02-04T05:42:07Z<p>Wayneliang: Merged content into main Lomustine page and replaced this page with a redirect</p>
<hr />
<div>#REDIRECT [[Lomustine_(CCNU)]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Lomustine_(CCNU)&diff=54393Lomustine (CCNU)2022-02-04T05:38:34Z<p>Wayneliang: Incorporated Lomustine Dosing Chart</p>
<hr />
<div>==General information==<br />
Class/mechanism: Nitrosourea, alkylates DNA and RNA and may inhibit certain key enzymatic reactions by carbamoylation of amino acids in proteins.<ref name="insert">[https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017588s042lbl.pdf Lomustine (Ceenu) package insert]</ref><ref>[http://hemonc.org/docs/packageinsert/lomustine.pdf Lomustine (Ceenu) package insert (locally hosted backup)]</ref><br />
<br>Route: PO<br />
<br>Extravasation: n/a<br />
<br />
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information.<ref name="insert"></ref> <br />
<br />
==Diseases for which it is used==<br />
*[[Acute myeloid leukemia]]<br />
*[[Anaplastic glioma]]<br />
*[[CNS lymphoma]]<br />
*[[Glioblastoma]]<br />
*[[Low-grade glioma]]<br />
*[[Medulloblastoma]]<br />
<br />
==Diseases for which it was used==<br />
*[[Hodgkin lymphoma_-_historical|Hodgkin lymphoma]]<br />
*[[Non-small cell lung cancer_-_historical|Non-small cell lung cancer]]<br />
<br />
==Patient drug information==<br />
*[https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/017588s042lbl.pdf Lomustine (Ceenu) package insert]<ref name="insert"></ref><br />
*[http://chemocare.com/bio/lomustine.asp Lomustine (Ceenu) patient drug information (Chemocare)]<ref>[http://chemocare.com/bio/lomustine.asp Lomustine (Ceenu) patient drug information (Chemocare)]</ref><br />
*[http://www.uptodate.com/contents/lomustine-patient-drug-information Lomustine (Ceenu) patient drug information (UpToDate)]<ref>[http://www.uptodate.com/contents/lomustine-patient-drug-information Lomustine (Ceenu) patient drug information (UpToDate)]</ref><br />
<br />
==History of changes in FDA indication==<br />
*8/4/1976: Initial approval<br />
*4/30/2009: (oldest available label at Drugs@FDA) has been shown to be useful as a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in [[:Category:CNS cancers|brain tumors]]—both primary and metastatic, in patients who have already received appropriate surgical and/or radiotherapeutic procedures.<br />
*4/30/2009: (oldest available label at Drugs@FDA) has been shown to be useful as a single agent in addition to other treatment modalities, or in established combination therapy with other approved chemotherapeutic agents in [[Hodgkin lymphoma|Hodgkin’s Disease]]—secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy, or who fail to respond to primary therapy.<br />
<br />
==Also known as==<br />
*'''Generic names:''' CCNU<br />
*'''Brand names:''' CeeNu, Gleostine<br />
**In 10/2013, Bristol-Myers Squibb discontinued production of their Lomustine brand name, CeeNu.<ref>[http://www.ashp.org/DrugShortages/NotAvailable/bulletin.aspx?id=1023 Discontinued drug bulletin: Lomustine capsules (American Society of Health-System Pharmacists)]</ref> Lomustine is currently supplied as Gleostine by NextSource Biotechnology LLC.<ref>[http://www.elabs6.com/content/12347425/EP298498RDNW/nextsource5.index.html NextSource Biotechnology Lomustine (CCNU) update]</ref><br />
<br />
==COG ACNS0331 Lomustine Dosing Nomogram==<br />
<br />
===Available Capsule Sizes===<br />
*10 mg <br />
*40 mg <br />
*100 mg<br />
<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Body Surface Area (m<sup>2</sup>)<br />
! style="width: 25%" |Ideal Dose (75 mg/m<sup>2</sup>/day once daily)<br />
! style="width: 25%" |Actual Dose to be Given<br />
|-<br />
|2.0<br />
|150 mg,<br />
|150 mg<br />
|-<br />
|1.9<br />
|143<br />
|140<br />
|-<br />
|1.8<br />
|135<br />
|130<br />
|-<br />
|1.7<br />
|128<br />
|130<br />
|-<br />
|1.6<br />
|120<br />
|120<br />
|-<br />
|1.5<br />
|112<br />
|110<br />
|-<br />
|1.4<br />
|105<br />
|100<br />
|-<br />
|1.3<br />
|98<br />
|100<br />
|-<br />
|1.2<br />
|90<br />
|90<br />
|-<br />
|1.1<br />
|82<br />
|80<br />
|-<br />
|1.0<br />
|75<br />
|80<br />
|-<br />
|0.95<br />
|71<br />
|70<br />
|-<br />
|0.9<br />
|68<br />
|70<br />
|-<br />
|0.85<br />
|64<br />
|60<br />
|-<br />
|0.8<br />
|60<br />
|60<br />
|-<br />
|0.75<br />
|56<br />
|60<br />
|-<br />
|0.7<br />
|53<br />
|50<br />
|-<br />
|0.65<br />
|49<br />
|50<br />
|-<br />
|0.6<br />
|45<br />
|40<br />
|-<br />
|0.55<br />
|41<br />
|40<br />
|-<br />
|0.5<br />
|38<br />
|40<br />
|-<br />
|0.45<br />
|34<br />
|30<br />
|-<br />
|0.4<br />
|30<br />
|30<br />
|-<br />
|0.35<br />
|26<br />
|30<br />
|-<br />
|0.3<br />
|23<br />
|20<br />
|}<br />
<br />
==References==<br />
<references/><br />
<br />
[[Category:Drugs]]<br />
[[Category:Oral medications]]<br />
<br />
[[Category:Nitrosoureas]]<br />
<br />
[[Category:Acute myeloid leukemia medications]]<br />
[[Category:Anaplastic glioma medications]]<br />
[[Category:CNS lymphoma medications]]<br />
[[Category:Glioblastoma medications]]<br />
[[Category:Low-grade glioma medications]]<br />
[[Category:Medulloblastoma medications]]<br />
<br />
[[Category:FDA approved in 1976]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Medulloblastoma&diff=54392Medulloblastoma2022-02-04T05:31:15Z<p>Wayneliang: Added space between COG and protocol identifier</p>
<hr />
<div>{{#lst:Section editor transclusions|peds-neuro}}<br />
''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[Medulloblastoma_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''<br />
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
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{{TOC limit|limit=3}}<br />
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<br />
=COG ACNS0331 Standard Dose CSRT/Reduced Volume Boost to Tumor Bed=<br />
*Ages 3+<br />
*All patients must begin therapy within 31 days of surgery. <br />
==Chemoradiotherapy==<br />
===XRT===<br />
*Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions<br />
*Tumor Bed Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions.<br />
===Chemotherapy===<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 8, 15, 22, 29, 36, and 43 (Once a week starting one week after CSRT begins).<br />
**Round vincristine '''down''' to the nearest 0.1 mg.<br />
'''7-week course'''<br />
====References====<br />
#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. [https://doi.org/10.1200/JCO.20.02730 link to original article] NCT00085735<br />
==Maintenance Regimen A==<br />
Cycles 1, 2, 4, 5, 7, 8<br />
===Chemotherapy===<br />
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1<br />
*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V).<br />
**[[Pediatric Lomustine Dosing Chart]]<br />
**Give [[Lomustine (CCNU)]] with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age. <br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, and 15.<br />
**Dose rounded '''down''' to the nearest 0.1 mg. <br />
**Can be given IV push over 1-minute or by infusion via minibag as per institution policy.<br />
'''6-week cycle'''<br />
====References====<br />
#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. [https://doi.org/10.1200/JCO.20.02730 link to original article] NCT00085735<br />
<br />
<br />
==Maintenance Regimen B==<br />
Cycles 3, 6, and 9<br />
===Chemotherapy===<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1 and 2. <br />
*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup>/dose IV over 15 to 30 minutes on Days 1 and 2<br />
**Dose given at least 15 minutes prior to or at the same time as [[Cyclophosphamide (Cytoxan)]] and repeated at 4 and 8 hours post [[Cyclophosphamide (Cytoxan)]].<br />
**Can be given via continuous infusion starting 15-30 minutes before or at the same time as [[Cyclophosphamide (Cytoxan)]] and finished no sooner than 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, and 8.<br />
**Dose rounded '''down''' to the nearest 0.1 mg.<br />
**Can be given IV push over 1-minute or by infusion via minibag as per institution policy.<br />
'''6-week course'''<br />
====References====<br />
#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. [https://doi.org/10.1200/JCO.20.02730 link to original article] NCT00085735<br />
=COG ACNS0331 Standard Dose CSRT/Standard Volume Boost=<br />
*Ages 3+<br />
*All patients must begin therapy within 31 days of surgery. <br />
==Chemoradiotherapy==<br />
===XRT===<br />
*Craniospinal [[External beam radiotherapy]] 23.4 Gy in 13 daily fractions. <br />
*Posterior Fossa Boost [[External beam radiotherapy]] 30.6 Gy in 17 daily fractions.<br />
===Chemotherapy===<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 8, 15, 22, 29, 36, and 43 (Once a week starting one week after CSRT begins).<br />
**Round vincristine '''down''' to the nearest 0.1 mg.<br />
'''7-week course'''<br />
====References====<br />
#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. [https://doi.org/10.1200/JCO.20.02730 link to original article] NCT00085735<br />
==Maintenance Regimen A==<br />
Cycles 1, 2, 4, 5, 7, 8<br />
===Chemotherapy===<br />
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1<br />
*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 1 on an empty stomach (at least 2 hours after food) preferably at bedtime (reduce N/V).<br />
**[[Pediatric Lomustine Dosing Chart]]<br />
**Give [[Lomustine (CCNU)]] with at least 8 oz of fluids for children > 3 years old and at least 4 oz of fluids for children < 3 years of age. <br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, and 15.<br />
**Dose rounded '''down''' to the nearest 0.1 mg. <br />
**Can be given IV push over 1-minute or by infusion via minibag as per institution policy.<br />
'''6-week cycle'''<br />
====References====<br />
#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. [https://doi.org/10.1200/JCO.20.02730 link to original article] NCT00085735<br />
<br />
<br />
==Maintenance Regimen B==<br />
Cycles 3, 6, and 9<br />
===Chemotherapy===<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV given over 1 hour on Days 1 and 2. <br />
*[[Mesna (Mesnex)]] 360 mg/m<sup>2</sup>/dose IV over 15 to 30 minutes on Days 1 and 2<br />
**Dose given at least 15 minutes prior to or at the same time as [[Cyclophosphamide (Cytoxan)]] and repeated at 4 and 8 hours post [[Cyclophosphamide (Cytoxan)]].<br />
**Can be given via continuous infusion starting 15-30 minutes before or at the same time as [[Cyclophosphamide (Cytoxan)]] and finished no sooner than 8 hours after the end of the [[Cyclophosphamide (Cytoxan)]] infusion.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, and 8.<br />
**Dose rounded '''down''' to the nearest 0.1 mg.<br />
**Can be given IV push over 1-minute or by infusion via minibag as per institution policy.<br />
'''6-week course'''<br />
====References====<br />
#'''COG ACNS0331:''' Michalski JM, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy PC, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, JBooth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy with Chemotherapy for Newly Diagnosed Average Risk Medulloblastoma. Journal of Clinical Oncology 39, no. 24 (August 20, 2021) 2685-2697. [https://doi.org/10.1200/JCO.20.02730 link to original article] NCT00085735<br />
=COG ACNS0332 Regimen A=<br />
==Chemoradiotherapy==<br />
===XRT===<br />
*Craniospinal [[External beam radiotherapy]] 36 Gy in 20 daily fractions (Monday - Friday). <br />
*Posterior Fossa Boost [[External beam radiotherapy]] 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy).<br />
For additional boost details, such as technique and location, please see full protocol as this depends on site of metastases and disease stage. <br />
===Chemotherapy===<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15, 22, 29, and 36 (Once a week starting within one week of the start of CSRT).<br />
**Round vincristine '''down''' to the nearest 0.1 mg.<br />
'''6-Week Course'''<br />
===References===<br />
#'''COG ACNS0332:''' Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. [https://doi.org/10.1200/jco.2017.76.4720 link to original article] NCT00392327<br />
#'''COG ACNS0332:''' Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] NCT00392327<br />
==Maintenance Cycle==<br />
Begin each cycle on Day 29 and when ANC ≥ 750/μL, platelets ≥ 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours for a total of 6 cycles. <br />
===Chemotherapy===<br />
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on days 1 and 8.<br />
**Round vincristine '''down''' to the nearest 0.1 mg.<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 1 hour once on days 2 and 3.<br />
**[[Cyclophosphamide (Cytoxan)]] should be given at least 24 hours after Cisplatin on day 2. <br />
'''28-Day Course'''<br />
===References===<br />
#'''COG ACNS0332:''' Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. [https://doi.org/10.1200/jco.2017.76.4720 link to original article] NCT00392327<br />
#'''COG ACNS0332:''' Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] NCT00392327<br />
=COG ACNS0332 Regimen B=<br />
==Chemoradiotherapy==<br />
===XRT===<br />
*Craniospinal [[External beam radiotherapy]] 36 Gy in 20 daily fractions (Monday - Friday). <br />
*Posterior Fossa Boost [[External beam radiotherapy]] 19.8 Gy in 11 daily fractions (Cumulative dose of 55.8 Gy).<br />
For additional boost details, such as technique and location, please see full protocol as this depends on site of metastases and disease stage. <br />
===Chemotherapy===<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on day 1, 8, 15, 22, 29, and 36 (Once a week starting within one week of the start of CSRT).<br />
**Round vincristine '''down''' to the nearest 0.1 mg.<br />
**Administer prior to Carboplatin<br />
*[[Carboplatin (Paraplatin)]] 35 mg/m<sup>2</sup> IV over 15 minutes given daily 1 - 4 hours prior to radiation therapy (Total of 30 doses).<br />
**[[Carboplatin (Paraplatin)]] first dose administered on the first day of radiation therapy.<br />
**[[Carboplatin (Paraplatin)]] should be '''HELD''' if radiation treatment is not given.<br />
**Since there are 31 fractions of radiation, No [[Carboplatin (Paraplatin)]] should be given prior to the final radiation fraction. <br />
'''6-Week Course'''<br />
#'''COG ACNS0332:''' Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. [https://doi.org/10.1200/jco.2017.76.4720 link to original article] NCT00392327<br />
#'''COG ACNS0332:''' Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] NCT00392327<br />
==Maintenance Cycle==<br />
Begin each cycle on Day 29 and when ANC ≥ 750/μL, platelets ≥ 75,000/μL, and the patient has been off of myeloid growth factor for at least 24 hours for a total of 6 cycles. <br />
===Chemotherapy===<br />
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute or IV infusion (per institution) once on days 1 and 8.<br />
**Round vincristine '''down''' to the nearest 0.1 mg.<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 1 hour once on days 2 and 3.<br />
**[[Cyclophosphamide (Cytoxan)]] should be given at least 24 hours after Cisplatin on day 2. <br />
'''28-Day Course'''<br />
===References===<br />
#'''COG ACNS0332:''' Hwang EI, Kool M, Capper D, Chavez L, Brabetz S, Williams-Hughes C, Billups C, Heier L, Jaju A, Michalski J, Li Y, Leary S, Zhou T, von Deimling A, Jones DTW, Fouladi M, Pollack IF, Gajjar A, Packer RJ, Pfister SM, Olson JM. Extensive Molecular and Clinical Heterogeneity in Patients with Histologically Diagnosed CNS-PNET Treated as a Single Entity: A Report From the Children's Oncology Group Randomized ACNS0332 Trial. Journal of Clinical Oncology 2018 Oct 17:JCO2017764720. [https://doi.org/10.1200/jco.2017.76.4720 link to original article] NCT00392327<br />
#'''COG ACNS0332:''' Leary SES, Packer RJ, LiY, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L, Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA, Olson JM. Efficacy of Carboplatin and Isotretinoin in Children with High-risk Medulloblastoma: A Randomized Clinical Trial from the Children's Oncology Group. JAMA Oncology 2021 Sep 1; 7(9): 1313-1321. [https://doi.org/10.1001/jamaoncol.2021.2224 link to original article] NCT00392327<br />
=Adjuvant therapy=<br />
==Carboplatin, Cyclophosphamide, Etoposide, Methotrexate, Vincristine {{#subobject:ea894c|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:9134b2|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.nejm.org/doi/10.1056/NEJMoa042176 Rutkowski et al. 2005]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
====Preceding treatment====<br />
*[[Surgery#Surgical_resection|Surgery]]<br />
====Chemotherapy====<br />
*[[Carboplatin (Paraplatin)]]<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Etoposide (Vepesid)]]<br />
*[[Methotrexate (MTX)]]<br />
*[[Vincristine (Oncovin)]]<br />
===References===<br />
# Rutkowski S, Bode U, Deinlein F, Ottensmeier H, Warmuth-Metz M, Soerensen N, Graf N, Emser A, Pietsch T, Wolff JE, Kortmann RD, Kuehl J. Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. N Engl J Med. 2005 Mar 10;352(10):978-86. [https://www.nejm.org/doi/10.1056/NEJMoa042176 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15758008 PubMed]<br />
==Cisplatin, Lomustine, Vincristine {{#subobject:3d292d|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:2067d9|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2006.06.4980 Packer et al. 2006 (COG A9961)]<br />
|1996-2000<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|Cisplatin, Cyclophosphamide, Vincristine<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS<br />
|-<br />
|}<br />
''Note: neither the cycle length nor the exact dosing instructions for vincristine are clear from the manuscript.''<br />
====Preceding treatment====<br />
*[[Surgery#Surgical_resection|Surgery]], then radiotherapy<br />
====Chemotherapy====<br />
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1<br />
*[[Lomustine (CCNU)]] 75 mg/m<sup>2</sup> PO once on day 0<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 7, 14<br />
'''8 cycles (see note)'''<br />
===References===<br />
# '''COG A9961:''' Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006 Sep 1;24(25):4202-8. [https://doi.org/10.1200/JCO.2006.06.4980 link to original article] '''contains partially verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/16943538 PubMed] NCT00002875<br />
==Cyclophosphamide & Vincristine/Cisplatin & Etoposide {{#subobject:852402|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Protocol {{#subobject:1a3d99|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;"<br />
!style="width: 25%"|Study<br />
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.nejm.org/doi/10.1056/NEJM199306173282401 Duffner et al. 1993]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
''Total duration of treatment is 12 to 24 months.''<br />
====Preceding treatment====<br />
*[[Surgery#Surgical_resection|Surgical resection]] or biopsy<br />
====Chemotherapy, part 1====<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Vincristine (Oncovin)]]<br />
'''28-day cycle for 2 cycles, alternating with part 2'''<br />
====Chemotherapy, part 2====<br />
*[[Cisplatin (Platinol)]]<br />
*[[Etoposide (Vepesid)]]<br />
'''28-day cycle for 1 cycle, alternating with part 1'''<br />
===References===<br />
# Duffner PK, Horowitz ME, Krischer JP, Friedman HS, Burger PC, Cohen ME, Sanford RA, Mulhern RK, James HE, Freeman CR, Seidel FG, Kun LE. Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med. 1993 Jun 17;328(24):1725-31. [https://www.nejm.org/doi/10.1056/NEJM199306173282401 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8388548 PubMed]<br />
==VCP {{#subobject:3dy31n|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VCP: '''<u>V</u>'''incristine, '''<u>C</u>'''CNU (Lomustine), '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:ytacgn|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
!style="width: 20%"|Study<br />
!style="width: 20%"|Years of enrollment<br />
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]<br />
!style="width: 20%"|Comparator<br />
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/jco.1999.17.3.832 Zeltzer et al. 1999 (CCG-921)]<br />
|1986-1992<br />
| style="background-color:#1a9851" |Phase 3 (C)<br />
|8-in-1<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
====Preceding treatment====<br />
*[[Surgery#Surgical_resection|Surgery]], then Vincristine & RT<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Lomustine (CCNU)]] 100 mg/m<sup>2</sup> IV once on day 1<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 14<br />
'''6-week cycle for 8 cycles'''<br />
===References===<br />
#'''CCG-921:''' Zeltzer PM, Boyett JM, Finlay JL, Albright AL, Rorke LB, Milstein JM, Allen JC, Stevens KR, Stanley P, Li H, Wisoff JH, Geyer JR, McGuire-Cullen P, Stehbens JA, Shurin SB, Packer RJ. Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. J Clin Oncol. 1999 Mar;17(3):832-45. [https://doi.org/10.1200/jco.1999.17.3.832 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/10071274/ PubMed]<br />
[[Category:Medulloblastoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Pediatric neurologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=User:Wayneliang&diff=54376User:Wayneliang2022-02-03T19:30:33Z<p>Wayneliang: changed doximity link (was broken)</p>
<hr />
<div>[[File:Wayne Liang.jpg|alt=|thumb|Wayne Liang, MD MS]]<br />
Wayne Liang, MD MS FAMIA FAAP is a pediatric hematology/oncology attending physician and physician informaticist at Children's Healthcare of Atlanta, and Assistant Professor of Pediatrics at Emory University, with a clinical focus in pediatric bone marrow transplant. Dr. Liang focuses on clinical informatics for cancer, bone marrow transplant, and genomic precision medicine. He participates as a clinical investigator for childhood cancer clinical trials through the [https://www.childrensoncologygroup.org/ Children's Oncology Group] and other cooperative groups. Dr. Liang is board-certified in Pediatrics, Pediatric Hematology/Oncology, and Clinical Informatics (ABPM).<br />
Wayne Liang, MD is the HemOnc.org Section Editor of [[:Category:Pediatric cancers|Pediatric Leukemia & Lymphoma]].<br />
==External Links==<br />
*[https://twitter.com/WayneLiangMD Twitter.com/WayneLiangMD]<br />
*[https://linkedin.com/in/wayneliang LinkedIn]<br />
*[https://www.doximity.com/cv/wayneliang Doximity]</div>Waynelianghttps://hemonc.org/w/index.php?title=File:Liang.jpg&diff=52727File:Liang.jpg2021-10-04T21:07:14Z<p>Wayneliang: Wayneliang uploaded a new version of File:Liang.jpg</p>
<hr />
<div></div>Waynelianghttps://hemonc.org/w/index.php?title=User:Wayneliang&diff=52726User:Wayneliang2021-10-04T21:06:08Z<p>Wayneliang: New headshot</p>
<hr />
<div>[[File:Wayne Liang.jpg|alt=|thumb|Wayne Liang, MD MS]]<br />
Wayne Liang, MD MS FAMIA FAAP is a pediatric hematology/oncology attending physician and physician informaticist at Children's Healthcare of Atlanta, and Assistant Professor of Pediatrics at Emory University, with a clinical focus in pediatric bone marrow transplant. Dr. Liang focuses on clinical informatics for cancer, bone marrow transplant, and genomic precision medicine. He participates as a clinical investigator for childhood cancer clinical trials through the [https://www.childrensoncologygroup.org/ Children's Oncology Group] and other cooperative groups. Dr. Liang is board-certified in Pediatrics, Pediatric Hematology/Oncology, and Clinical Informatics (ABPM). <br />
Wayne Liang, MD is the HemOnc.org Section Editor of [[:Category:Pediatric cancers|Pediatric Leukemia & Lymphoma]].<br />
==External Links==<br />
*[https://twitter.com/WayneLiangMD Twitter.com/WayneLiangMD]<br />
*[https://linkedin.com/in/wayneliang LinkedIn]<br />
*[http://www.wayneliangmd.com/ Doximity]</div>Waynelianghttps://hemonc.org/w/index.php?title=File:Wayne_Liang.jpg&diff=52725File:Wayne Liang.jpg2021-10-04T21:05:51Z<p>Wayneliang: </p>
<hr />
<div>New headshot</div>Waynelianghttps://hemonc.org/w/index.php?title=User:Wayneliang&diff=51891User:Wayneliang2021-08-18T12:02:36Z<p>Wayneliang: Role change</p>
<hr />
<div>[[File:Liang.jpg|thumb|Wayne Liang, MD MS]]<br />
Wayne Liang, MD MS FAMIA FAAP is a pediatric hematology/oncology attending physician and physician informaticist at Children's Healthcare of Atlanta, and Assistant Professor of Pediatrics at Emory University, with a clinical focus in pediatric bone marrow transplant. Dr. Liang focuses on clinical informatics for cancer, bone marrow transplant, and genomic precision medicine. He participates as a clinical investigator for childhood cancer clinical trials through the [https://www.childrensoncologygroup.org/ Children's Oncology Group] and other cooperative groups. Dr. Liang is board-certified in Pediatrics, Pediatric Hematology/Oncology, and Clinical Informatics (ABPM). <br />
<br />
Wayne Liang, MD <S is the HemOnc.org Section Editor of [[:Category:Pediatric cancers|Pediatric Oncology]].<br />
<br />
==External Links==<br />
<br />
*[https://twitter.com/WayneLiangMD Twitter.com/WayneLiangMD]<br />
*[http://linkedin.com/in/wayneliang LinkedIn]<br />
*[http://www.wayneliangmd.com/ Doximity]</div>Waynelianghttps://hemonc.org/w/index.php?title=B-cell_acute_lymphoblastic_leukemia,_pediatric&diff=51451B-cell acute lymphoblastic leukemia, pediatric2021-07-07T18:02:05Z<p>Wayneliang: </p>
<hr />
<div>{| class="wikitable" style="text-align:center; width:50%;"<br />
! colspan="2" align="center" style="color:white; font-size:125%; background-color:#4a1486" |'''Section editor'''<br />
|-<br />
| style="background-color:#F0F0F0" |[[File:Liang.jpg|frameless|upright=0.3|center]]<br />
|<big>[[User:Wayneliang|Wayne H. Liang, MD, MS, FAMIA]]<br>UAB<br>Birmingham, AL</big><br>[https://www.linkedin.com/in/wayneliang/ LinkedIn]<br>[[File:Social-twitter-icon.png|frameless|upright=0.1]] [https://twitter.com/WayneLiangMD WayneLiangMD]<br />
|-<br />
|}<br />
<big>''This page contains studies that are specific to pediatric populations. For the more general B-cell acute lymphoblastic leukemia page, including regimens for adolescents and young adults, follow [[B-cell acute lymphoblastic leukemia|this link]].''</big><br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=3}}<br />
=Guidelines=<br />
=="How I Treat"==<br />
<br />
*'''2020:''' Hunger & Raetz. [https://doi.org/10.1182/blood.2019004043 How I treat relapsed acute lymphoblastic leukemia in the pediatric population]<br />
<br />
==[https://www.nccn.org/ NCCN]==<br />
<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_all.pdf NCCN Guidelines - Pediatric Acute Lymphoblastic Leukemia]<br />
<br />
=COG AALL0932=<br />
'''For Standard Risk B-ALL'''<br />
<br />
==Induction==<br />
===Pegaspargase, Vincristine, Dexamethasone {{#subobject:15hgu1|Regimen=1}}===<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:e8uyt1|Variant=1}}====<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030893/ Maloney et al. 2019 (COG AALL0331)]<br />
|2005-2010<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
''Note: there are very minor differences in timing between protocols; see papers for details.''<br />
=====Chemotherapy=====<br />
<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV once over 1 - 2 hours on day 4<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22<br />
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 28<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Cytarabine (Ara-C)]] IT once on day 0<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Initial Dose<br />
|-<br />
|1 - 1.99 years<br />
|30 mg<br />
|-<br />
|2 - 2.99 years<br />
|50 mg<br />
|-<br />
|≥ 3 years<br />
|70 mg<br />
|}<br />
CNS2 Patients will receive an additional dose of [[Cytarabine (Ara-C)]] IT on either day 4, 5, or 6, followed by [[Methotrexate (MTX)]] IT on day 8 and then another dose of [[Cytarabine (Ara-C)]] IT on either day 11 or 12 according to the following dosing.<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Subsequent Doses<br />
|-<br />
|1 - 1.99<br />
|20 mg<br />
|-<br />
|2 - 2.99<br />
|30 mg<br />
|-<br />
|≥ 3<br />
|40 mg<br />
|}<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 8 & 29<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
=====DS Arm=====<br />
<br />
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> x 2 doses given 48 and 60 hours after the lumbar puncture on days 10-11 and 31-32<br />
<br />
<br />
'''35-day course'''<br />
<br />
=====Subsequent treatment=====<br />
<br />
*COG AALL0331, M2 marrow or M1 marrow with MRD of at least 1% at day 29: Extended induction<br />
*COG AALL0932: [[#Mercaptopurine_.26_Vincristine|6-MP & Vincristine consolidation]]<br />
<br />
====References====<br />
<br />
#'''COG AALL0331:''' Maloney KW, Devidas M, Wang C, Mattano LA, Friedmann AM, Buckley P, Borowitz MJ, Carroll AJ, Gastier-Foster JM, Heerema NA, Kadan-Lottick N, Loh ML, Matloub YH, Marshall DT, Stork LC, Raetz EA, Wood B, Hunger SP, Carroll WL, Winick NJ. Outcome in Children With Standard-Risk B-Cell Acute Lymphoblastic Leukemia: Results of Children's Oncology Group Trial AALL0331. J Clin Oncol. 2020 Feb 20;38(6):602-612. Epub 2019 Dec 11. [https://doi.org/10.1200/jco.19.01086 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030893/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/31825704/ PubMed] NCT00103285<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
==Consolidation==<br />
'''For AR B-ALL patients, LR-C Arm, and B-LLy'''<br />
===Mercaptopurine & Vincristine {{#subobject:171gc1|Regimen=1}}===<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:1ygvt1|Variant=1}}====<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
=====Preceding treatment=====<br />
<br />
*[[#Pegaspargase.2C_Vincristine.2C_Dexamethasone|Pegaspargase, Vincristine, Dexamethasone induction]]<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/day PO on days 1 to 28<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1, 8, 15<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
=====DS Arm=====<br />
<br />
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> x 2 doses given 48 and 60 hours after the lumbar puncture on days 3-4, 10-11, and 17-18.<br />
<br />
<br />
'''28-day course'''<br />
<br />
=====Subsequent treatment=====<br />
<br />
*[[#Methotrexate_.26_Vincristine|MTX & Vincristine interim maintenance]]<br />
<br />
====References====<br />
<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
==Interim Maintenance I==<br />
'''For AR B-ALL patients, LR-C Arm, and B-LLy'''<br />
===Methotrexate & Vincristine {{#subobject:0ae09f|Regimen=1}}===<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:57f39d|Variant=1}}====<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ Matloub et al. 2011 (COG CCG-1991)]<br />
|2000-2005<br />
| style="background-color:#1a9851" |Phase III (E-de-esc)<br />
|Mercaptopurine, MTX, Vincristine, Dexamethasone<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|}<br />
=====Preceding treatment=====<br />
<br />
*COG AALL0932: [[#Mercaptopurine_.26_Vincristine|6-MP & Vincristine consolidation]]<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Methotrexate (MTX)]] 100 mg/m<sup>2</sup> IV once on day 1, then 150 mg/m<sup>2</sup> IV once on day 11, then 200 mg/m<sup>2</sup> IV once on day 21, then 250 mg/m<sup>2</sup> IV once on day 31, then 300 mg/m<sup>2</sup> IV once on day 41<br />
**Given over 2 - 5 minutes (undiluted) or over 10 - 15 minutes (diluted).<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once on day 31<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
=====DS Arm=====<br />
<br />
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> x 2 doses given 48 and 60 hours after the lumbar puncture on days 33-34<br />
<br />
<br />
'''8-week course'''<br />
<br />
=====Subsequent treatment=====<br />
<br />
*COG AALL0932: [[#AALL0932_delayed_intensification|AALL0932 delayed intensification]]<br />
<br />
====References====<br />
<br />
#'''COG CCG-1991:''' Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. [http://www.bloodjournal.org/content/118/2/243.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21562038 PubMed] NCT00005945<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
==Delayed Intensification==<br />
'''For AR B-ALL patients, LR-C Arm, and B-LLy'''<br />
===AALL0932 delayed intensification {{#subobject:17185g|Regimen=1}}===<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:1y47gc|Variant=1}}====<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
=====Preceding treatment=====<br />
<br />
*[[#Methotrexate_.26_Vincristine|MTX & Vincristine interim maintenance]]<br />
<br />
====Chemotherapy====<br />
<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 - 60 minutes once on day 29<br />
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup>/day SC or IV over 1 - 30 minutes on days 29 to 32, 36 to 39<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push/infusion over 1 - 15 minutes once per day on days 1, 8, 15<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 - 2 hours once on day 4<br />
*[[Thioguanine (Tabloid)]] 60 mg/m<sup>2</sup>/day PO once per day on days 29 to 42<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15<br />
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup>/dose PO twice daily on days 1 to 7, 15 to 21 (10 mg/m<sup>2</sup>/day)<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1 & 29<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
=====DS Arm=====<br />
<br />
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> x 2 doses given 48 and 60 hours after the lumbar puncture on days 3-4 and 31-32.<br />
<br />
<br />
'''8-week course'''<br />
<br />
=====Subsequent treatment=====<br />
<br />
*[[#Methotrexate_.26_Vincristine_2|MTX & Vincristine interim maintenance II]]<br />
<br />
====References====<br />
<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
==Interim Maintenance II==<br />
'''For AR B-ALL patients, LR-C Arm, and B-LLy'''<br />
===Methotrexate & Vincristine {{#subobject:0ae09f|Regimen=1}}===<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:57f39d|Variant=1}}====<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ Matloub et al. 2011 (COG CCG-1991)]<br />
|2000-2005<br />
| style="background-color:#1a9851" |Phase III (E-de-esc)<br />
|Mercaptopurine, MTX, Vincristine, Dexamethasone<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|}<br />
=====Preceding treatment=====<br />
<br />
*COG AALL0932: [[#Mercaptopurine_.26_Vincristine|6-MP & Vincristine consolidation]]<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Methotrexate (MTX)]] 100 mg/m<sup>2</sup> IV once on day 1, then 150 mg/m<sup>2</sup> IV once on day 11, then 200 mg/m<sup>2</sup> IV once on day 21, then 250 mg/m<sup>2</sup> IV once on day 31, then 300 mg/m<sup>2</sup> IV once on day 41<br />
**Given over 2 - 5 minutes (undiluted) or over 10 - 15 minutes (diluted).<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once on day 31<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
=====DS Arm=====<br />
<br />
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> x 2 doses given 48 and 60 hours after the lumbar puncture on days 3-4 and 33-34.<br />
<br />
<br />
'''8-week course'''<br />
<br />
=====Subsequent treatment=====<br />
<br />
*COG AALL0932: [[#AALL0932_delayed_intensification|AALL0932 delayed intensification]]<br />
<br />
====References====<br />
<br />
#'''COG CCG-1991:''' Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. [http://www.bloodjournal.org/content/118/2/243.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21562038 PubMed] NCT00005945<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
==Maintenance Arm A and C==<br />
'''For AR B-ALL patients, and LR-C Arm'''<br />
===Vincristine/Dexamethasone Pulses {{#subobject:0ae09f|Regimen=1}}===<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:1y47gc|Variant=1}}====<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
=====Preceding treatment=====<br />
<br />
*COG AALL0932: [[#Methotrexate_.26_Vincristine|MTX & Vincristine interim maintenance]]<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, and 57<br />
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup>/dose PO twice daily on days 1 to 5, 29 - 33, and 578 - 61 (6 mg/m<sup>2</sup>/day)<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 to 84<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once on day 1<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''12-week cycles until total duration of therapy is 2 years for female and 3 years for male from the start of Interim I'''<br />
<br />
====References====<br />
<br />
#'''COG CCG-1991:''' Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. [http://www.bloodjournal.org/content/118/2/243.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21562038 PubMed] NCT00005945<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
==Maintenance Arm B and D==<br />
===Vincristine/Dexamethasone Pulses {{#subobject:0ae09f|Regimen=1}}===<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:1y47gc|Variant=1}}====<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
=====Preceding treatment=====<br />
<br />
*COG AALL0932: [[#Methotrexate_.26_Vincristine|MTX & Vincristine interim maintenance]]<br />
<br />
=====Chemotherapy=====<br />
<br />
*Currently maintenance arm B and D are also treated with [[Methotrexate (MTX)]] PO at 20 mg/m<sup>2</sup> (decreased from the starting dose of 40 mg/m<sup>2</sup>) on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, and 57<br />
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup>/dose PO twice daily on days 1 to 5, 29 - 33, and 57 - 61 (6 mg/m<sup>2</sup>/day)<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 to 84<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once on day 1<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''12-week cycles until total duration of therapy is 2 years for female and 3 years for male from the start of Interim I'''<br />
<br />
====References====<br />
<br />
#'''COG CCG-1991:''' Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. [http://www.bloodjournal.org/content/118/2/243.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21562038 PubMed] NCT00005945<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
==Maintenance Arm DS==<br />
'''For DS AR B-ALL patients and DS B-LLy'''<br />
===Vincristine/Dexamethasone {{#subobject:0ae09f|Regimen=1}}===<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:1y47gc|Variant=1}}====<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
=====Preceding treatment=====<br />
<br />
*COG AALL0932: [[#Methotrexate_.26_Vincristine|MTX & Vincristine interim maintenance]]<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1<br />
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup>/dose IV or PO twice daily on days 1 to 5 (6 mg/m<sup>2</sup>/day) (DO NOT TAPER)<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 to 84<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once on day 1<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''12-week cycles until total duration of therapy is 2 years for female and 3 years for male from the start of Interim I'''<br />
<br />
====References====<br />
<br />
#'''COG CCG-1991:''' Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. [http://www.bloodjournal.org/content/118/2/243.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21562038 PubMed] NCT00005945<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
==Arm LR-M==<br />
===Consolidation {{#subobject:0ae09f|Regimen=1}}===<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:1y47gc|Variant=1}}====<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Methotrexate (MTX)]] IV at 1000 mg/m<sup>2</sup> on days 8, 29, 50, 71, 92, and 113.<br />
<br />
Given as a 200 mg/m<sup>2</sup> bolus over 20 - 30 minutes followed by 800 mg/m<sup>2</sup> over 23.5 hours (initial bolus of 30 minutes) or 23 hours and 40 minutes (if initial bolus was over 20 minutes)<br />
<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 15, 22, 78, and 85.<br />
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup>/dose IV or PO twice daily on days 15 - 21, and 78 - 84. (6 mg/m<sup>2</sup>/day)<br />
*[[Mercaptopurine (6-MP)]] 50 mg/m<sup>2</sup>/dose PO once per day on days 1 to 33<br />
*[[Folinic acid (Leucovorin)]] 10 mg/m<sup>2</sup> x 2 doses PO or IV (given 48 and 60 hours after the START of MTX infusion, continuing until MTX level < 0.2 μM) on days 9 - 10, 30 - 31, 51 - 52, 72 - 73, 93 - 94, and 114 - 115.<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once on day 8, 29, 50, 71, 92, and 113 (To be delivered within 6 hours of the beginning of the IV MTX infusion, -6hr to + 6 hr)<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''19-week cycle'''<br />
<br />
====References====<br />
<br />
#'''COG CCG-1991:''' Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. [http://www.bloodjournal.org/content/118/2/243.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21562038 PubMed] NCT00005945<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
===Maintenance {{#subobject:0ae09f|Regimen=1}}===<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:1y47gc|Variant=1}}====<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
<br />
MTX DATES CHANGE DEPENDING ON CYCLE NUMBER<br />
<br />
Cycles 1 and 4:<br />
<br />
*[[Methotrexate (MTX)]] PO at 20 mg/m<sup>2</sup> on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 92, 99, and 106.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 and 8.<br />
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup>/dose PO twice daily on days 1 - 7. (6 mg/m<sup>2</sup>/day, do not taper)<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 - 112. (NOTE: Higher 6-MP dose than in consolidation)<br />
<br />
Cycles 2 and 5:<br />
<br />
*[[Methotrexate (MTX)]] PO at 20 mg/m<sup>2</sup> on days 1, 8, 15, 22, 29, 36, 43, 50, 64, 71, 78, 85, 92, 99, and 106.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 and 8.<br />
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup>/dose PO twice daily on days 1 - 7. (6 mg/m<sup>2</sup>/day, do not taper)<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 - 112. (NOTE: Higher 6-MP dose than in consolidation)<br />
<br />
Cycles 3 and 6:<br />
<br />
*[[Methotrexate (MTX)]] PO at 20 mg/m<sup>2</sup> on days 1, 8, 15, 22, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, and 106.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 and 8.<br />
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup>/dose PO twice daily on days 1 - 7. (6 mg/m<sup>2</sup>/day, do not taper)<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 - 112. (NOTE: Higher 6-MP dose than in consolidation)<br />
<br />
Cycle 7:<br />
<br />
*[[Methotrexate (MTX)]] PO at 20 mg/m<sup>2</sup> on days 1, 8, 15, 29, 22, 36, 43, 50, 57, and 64<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 and 8.<br />
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup>/dose PO twice daily on days 1 - 7. (6 mg/m<sup>2</sup>/day, do not taper)<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 - 70. (NOTE: Higher 6-MP dose than in consolidation)<br />
<br />
<br />
=====CNS prophylaxis=====<br />
<br />
DATES CHANGE DEPENDING ON CYCLE NUMBER<br />
<br />
Cycles 1 and 4: <br />
<br />
*[[Methotrexate (MTX)]] IT once on day 1 and 85.<br />
<br />
Cycles 2 and 5:<br />
<br />
*[[Methotrexate (MTX)]] IT once on day 57.<br />
<br />
Cycles 3 and 6:<br />
<br />
*[[Methotrexate (MTX)]] IT once on day 29.<br />
<br />
Cycle 7: <br />
NO MTX IT on Cycle 7<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''16-week cycles until a total duration of therapy of 2.5 years from the date of diagnosis is reached for both boys and girls.'''<br />
<br />
====References====<br />
<br />
#'''COG CCG-1991:''' Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. [http://www.bloodjournal.org/content/118/2/243.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21562038 PubMed] NCT00005945<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
==Maintenance Arm LLy==<br />
===Vincristine/Dexamethasone {{#subobject:0ae09f|Regimen=1}}===<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:1y47gc|Variant=1}}====<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
=====Preceding treatment=====<br />
<br />
*COG AALL0932: [[#Methotrexate_.26_Vincristine|MTX & Vincristine interim maintenance]]<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, and 57. (4 Week Intervals)<br />
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup>/dose PO twice daily on days 1 - 5, 29 - 33, and 57 - 61. (6 mg/m<sup>2</sup>/day) (DO NOT TAPER)<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 to 84.<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once on day 1<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''12-week cycles until total duration of therapy is 2 years for female and 3 years for male from the start of Interim I'''<br />
<br />
====References====<br />
<br />
#'''COG CCG-1991:''' Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. [http://www.bloodjournal.org/content/118/2/243.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21562038 PubMed] NCT00005945<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
=AALL1131=<br />
==Induction==<br />
===Daunorubicin, Pegaspargase, Vincristine, Dexamethasone {{#subobject:088146|Regimen=1}}===<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
''Note: the referenced publication does not specifically focus on induction; the full regimen is available as a protocol. Per the protocol, it is intended only for patients less than 10 years old.''<br />
====Chemotherapy====<br />
<br />
*[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV over 1 to 15 minutes once per day on days 1, 8, 15, 22<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 4<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22<br />
<br />
Patients < 10 years ONLY:<br />
<br />
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 14<br />
<br />
Patients ≥ 10 years ONLY:<br />
<br />
*[[Prednisone (Sterapred)]] 30 mg/m<sup>2</sup>/dose PO twice per day on days 1 to 28<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Cytarabine (Ara-C)]] as follows:<br />
**Ages 1 to 1.99: 30 mg IT once on day 1<br />
**Ages 2 to 2.99: 50 mg IT once on day 1<br />
**Age 3 and older: 70 mg IT once on day 1<br />
<br />
CNS2 Patients will receive an additional dose of [[Cytarabine (Ara-C)]] IT on either day 4, 5, or 6, and then another dose of [[Cytarabine (Ara-C)]] IT on either day 11 or 12 according to the following dosing.<br />
<br />
*[[Cytarabine (Ara-C)]] as follows:<br />
**Ages 1 to 1.99: 20 mg IT once<br />
**Ages 2 to 2.99: 30 mg IT once<br />
**Age 3 and older: 40 mg IT once<br />
<br />
*[[Methotrexate (MTX)]] as follows: (CNS3 also on Days 15 and 22)<br />
**Ages 1 to 1.99: 8 mg IT once per day on days 8 & 29<br />
**Ages 2 to 2.99: 10 mg IT once per day on days 8 & 29<br />
**Ages 3 to 8.99: 12 mg IT once per day on days 8 & 29<br />
**Age 9 and older: 15 mg IT once per day on days 8 & 29<br />
<br />
'''4-week course'''<br />
=====Subsequent treatment=====<br />
<br />
*See protocol for details of treatment beyond induction<br />
<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
==HR B-ALL==<br />
<br />
===Consolidation===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 - 60 minutes once on days 1 and 29<br />
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup>/day SC or IV over 1 - 30 minutes on days 1 - 4, 8 - 11, 29 - 32, 36 - 39.<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 - 2 hours once on days 15, and 43.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 15, 22, 43, and 50.<br />
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup>/dose PO once per day on days 1 - 14, and 29 - 42.<br />
<br />
======CNS prophylaxis======<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1, 8, 15, and 22.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''56-Day Course'''<br />
<br />
====References====<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
===Interim Maintenance with HD MTX===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29, and 43.<br />
*[[Mercaptopurine (6-MP)]] 25 mg/m<sup>2</sup>/dose PO once per day on days 1 - 56.<br />
*High Dose [[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV over 24 hours on days 1, 15, 29, and 43. <br />
**MTX 500 mg/m<sup>2</sup> IV infused over 30 minutes. This is followed, immediately, by MTX 4500 mg/m<sup>2</sup> given by continuous IV infusion over 23.5 hours.<br />
<br />
ANC must be ≥ 750/µL and platelets must be ≥ 75,000/µL prior to each dose of HD MTX<br />
<br />
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> x a minimum of 3 doses PO or IV (given at 42, 48, and 54 hours after the START of HD MTX infusion) on days 3 - 4, 17 - 18, 31 - 32, and 45 - 46.<br />
<br />
======CNS prophylaxis======<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1 and 29.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
When IT therapy and HD MTX are scheduled for the same day, deliver the IT therapy within 6 hours of the beginning of the IV MTX infusion. (hour -6 or +6, with 0 being the start of the MTX bolus). <br />
<br />
<br />
<br />
'''63-Day Course'''<br />
<br />
====References====<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
===Delayed Intensification===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push over 1 to 15 minutes once per day on days 1, 8, and 15.<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 to 2 hours once on days 4 and 43.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, and 50.<br />
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup> IV or PO twice per day on days 1 - 7 and 15 - 21.<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 - 60 minutes once on day 29 ONLY.<br />
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup>/day SC or IV over 1 - 30 minutes on days 29 - 32 and 36 - 39.<br />
*[[Thioguanine (Tabloid)]] 60 mg/m<sup>2</sup>/day PO once per day on days 29 to 42.<br />
<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1, 29, and 36.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
<br />
'''56-Day course'''<br />
<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
===Maintenance HR B-ALL===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
Cycles 1-4<br />
<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 - 84.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, and 57.<br />
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, 36, 43, 50, 57, 64, 71 and 78.<br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup>/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5, 29 - 33, and 57 - 61.<br />
<br />
Cycles 5 and Later<br />
<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 - 84.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, and 57.<br />
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71 and 78.<br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup>/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5, 29 - 33, and 57 - 61.<br />
<br />
=====CNS prophylaxis=====<br />
Cycles 1-4<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1 and 29.<br />
<br />
Cycles 5 and Later<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on day 1.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''12-Week Cycles repeated until total duration of therapy is 2 years for female patients and 3 years for male patients from the start of interim maintenance.'''<br />
<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
==VHR B-ALL==<br />
<br />
===Consolidation===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 15 and 43.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 15, 22, 43, and 50.<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 - 60 minutes once on day 1 and 29.<br />
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup>/day SC or IV over 1 - 30 minutes on days 1 - 4, 8 - 11, 29 - 32, and 36 - 39.<br />
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup>/dose PO once per day on days 1 - 14 and 29 - 42.<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1, 8, 15, and 22. (Omit days 15 and 22 for CNS3 Patients)<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''56-Day course'''<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
===Interim Maintenance I with HD MTX===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29, and 43.<br />
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup>/dose PO once per day on days 1 - 56.<br />
*High Dose [[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV over 24 hours on days 1, 15, 29, and 43. <br />
**MTX 500 mg/m<sup>2</sup> IV infused over 30 minutes. This is followed, immediately, by MTX 4500 mg/m<sup>2</sup> given by continuous IV infusion over 23.5 hours.<br />
<br />
ANC must be ≥ 750/µL and platelets must be ≥ 75,000/µL prior to each dose of HD MTX<br />
<br />
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> x a minimum of 3 doses PO or IV (given at 42, 48, and 54 hours after the START of HD MTX infusion) on days 3 - 4, 17 - 18, 31 - 32, and 45 - 46.<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1 and 29.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''28-Day course'''<br />
<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
===Delayed Intensification===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push over 1 to 15 minutes once per day on days 1, 8, and 15.<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 4 and 43.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, and 50.<br />
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup> IV or PO twice per day on days 1 - 7 and 15 - 21.<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 - 60 minutes once on day 29 ONLY.<br />
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup>/day SC or IV over 1 - 30 minutes on days 29 - 32 and 36 - 39.<br />
*[[Thioguanine (Tabloid)]] 60 mg/m<sup>2</sup>/day PO once per day on days 29 to 42.<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on day 1, 29, and 36.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''56-Day course'''<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
===Interim Maintenance II with Capizzi MTX===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on day 1, 11, 21, 31, and 41.<br />
*[[Methotrexate (MTX)]] 100 mg/m<sup>2</sup> IV over 2 - 5 minutes (undiluted) or over 10 - 15 minutes (diluted) on days 1, 150 mg/m<sup>2</sup> on day 11, 200 mg/m<sup>2</sup> on day 21, 250 mg/m<sup>2</sup> on day 31, and 300 mg/m<sup>2</sup> on day 41.<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 2 and 22.<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1 and 31.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''56-Day course'''<br />
<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
===VHR Arm Maintenance===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
====Radiotherapy====<br />
For Patients with CNS3 Disease<br />
<br />
*[[External_beam_radiotherapy|Total body irradiation (TBI)]] 1800 cGy in 10 fractions, during the first 4 weeks of Maintenance therapy and should be completed by day 29 of Maintenance.<br />
<br />
====Chemotherapy====<br />
<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 - 84.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, and 57.<br />
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, (29), 36, 43, 50, 57, 64, 71 and 78. (OMIT DAY 29 WHEN CNS RADIATION IS GIVEN, DUE TO IT MTX).<br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup>/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5, 29 - 33, and 57 - 61.<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on day 1 (also Day 29 of cycles 1 and 2, for patients who did NOT receive CNS Radiation).<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''12-Week Cycles repeated until total duration of therapy is 2 years for female patients and 3 years for male patients from the start of interim maintenance.'''<br />
<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
==Ph-Like B-ALL (Dasatinib Arm)==<br />
<br />
===Consolidation (Dasatinib Arm)===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 - 60 minutes once on days 1 and 29<br />
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup>/day SC or IV over 1 - 30 minutes on days 1 - 4, 8 - 11, 29 - 32, 36 - 39.<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 - 2 hours once on days 15, and 43.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 15, 22, 43, and 50.<br />
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup>/dose PO once per day on days 1 - 14, and 29 - 42.<br />
*[[Dasatinib (Sprycel)]] 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 56.<br />
<br />
======CNS prophylaxis======<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1, 8, 15, and 22.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
*[[Dasatinib (Sprycel)]] 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 56.<br />
<br />
'''56-Day Course'''<br />
<br />
====References====<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
===Interim Maintenance with HD MTX (Dasatinib Arm)===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29, and 43.<br />
*[[Mercaptopurine (6-MP)]] 25 mg/m<sup>2</sup>/dose PO once per day on days 1 - 56.<br />
*High Dose [[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV over 24 hours on days 1, 15, 29, and 43. <br />
**MTX 500 mg/m<sup>2</sup> IV infused over 30 minutes. This is followed, immediately, by MTX 4500 mg/m<sup>2</sup> given by continuous IV infusion over 23.5 hours.<br />
<br />
ANC must be ≥ 750/µL and platelets must be ≥ 75,000/µL prior to each dose of HD MTX<br />
<br />
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> x a minimum of 3 doses PO or IV (given at 42, 48, and 54 hours after the START of HD MTX infusion) on days 3 - 4, 17 - 18, 31 - 32, and 45 - 46.<br />
*[[Dasatinib (Sprycel)]] 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 63.<br />
<br />
======CNS prophylaxis======<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1 and 29.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
When IT therapy and HD MTX are scheduled for the same day, deliver the IT therapy within 6 hours of the beginning of the IV MTX infusion. (hour -6 or +6, with 0 being the start of the MTX bolus). <br />
<br />
<br />
'''63-Day Course'''<br />
<br />
====References====<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
===Delayed Intensification (Dasatinib Arm)===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push over 1 to 15 minutes once per day on days 1, 8, and 15.<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 to 2 hours once on days 4 and 43.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, and 50.<br />
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup> IV or PO twice per day on days 1 - 7 and 15 - 21.<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 - 60 minutes once on day 29 ONLY.<br />
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup>/day SC or IV over 1 - 30 minutes on days 29 - 32 and 36 - 39.<br />
*[[Thioguanine (Tabloid)]] 60 mg/m<sup>2</sup>/day PO once per day on days 29 to 42.<br />
*[[Dasatinib (Sprycel)]] 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 56.<br />
<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1, 29, and 36.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
<br />
'''56-Day course'''<br />
<br />
====References====<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article]<br />
<br />
===Interim Maintenance II with Capizzi MTX (Dasatinib Arm)===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on day 1, 11, 21, 31, and 41.<br />
*[[Methotrexate (MTX)]] 100 mg/m<sup>2</sup> IV over 2 - 5 minutes (undiluted) or over 10 - 15 minutes (diluted) on days 1, 150 mg/m<sup>2</sup> on day 11, 200 mg/m<sup>2</sup> on day 21, 250 mg/m<sup>2</sup> on day 31, and 300 mg/m<sup>2</sup> on day 41.<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 2 and 22.<br />
*[[Dasatinib (Sprycel)]] 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 56.<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1 and 31.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''56-Day course'''<br />
<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
===Maintenance (Dasatinib Arm)===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
====Radiotherapy====<br />
For Patients with CNS3 Disease<br />
<br />
*[[External_beam_radiotherapy|Total body irradiation (TBI)]] 1800 cGy in 10 fractions, during the first 4 weeks of Maintenance therapy and should be completed by day 29 of Maintenance.<br />
<br />
====Chemotherapy====<br />
<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 - 84.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 29, and 57.<br />
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, (29), 36, 43, 50, 57, 64, 71 and 78. (OMIT DAY 29 WHEN CNS RADIATION IS GIVEN, DUE TO IT MTX).<br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup>/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5, 29 - 33, and 57 - 61.<br />
*[[Dasatinib (Sprycel)]] 60 mg (rounded to the nearest 5 mg, max of 140 mg/day) PO once daily on days 1 to 84.<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on day 1 (also Day 29 of cycles 1 and 2, for patients who did NOT receive CNS Radiation).<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''12-Week Cycles repeated until total duration of therapy is 2 years for female patients and 3 years for male patients from the start of interim maintenance.'''<br />
<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
==DS HR B-ALL==<br />
<br />
===Induction===<br />
<br />
====Daunorubicin, Pegaspargase, Vincristine, Dexamethasone {{#subobject:088146|Regimen=1}}====<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
''Note: the referenced publication does not specifically focus on induction; the full regimen is available as a protocol. Per the protocol, it is intended only for patients less than 10 years old.''<br />
<br />
====Chemotherapy====<br />
<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 4<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, and 22<br />
<br />
Patients < 10 years ONLY:<br />
<br />
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 28 (DO NOT TAPER)<br />
<br />
Patients ≥ 10 years ONLY:<br />
<br />
*[[Prednisone (Sterapred)]] 30 mg/m<sup>2</sup>/dose PO twice per day on days 1 to 28 (DO NOT TAPER)<br />
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> x 2 doses PO (given at 48 and 60 hours after the lumbar puncture) on days 10 - 11 and 31 - 32. (CNS3 also on days 17 - 18 and 24 - 25).<br />
<br />
RER - M1 Marrow at Day 15<br />
<br />
*Add [[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV over 1 to 15 minutes once on days 15.<br />
<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Cytarabine (Ara-C)]] as follows:<br />
**Ages 1 to 1.99: 30 mg IT once on day 1<br />
**Ages 2 to 2.99: 50 mg IT once on day 1<br />
**Age 3 and older: 70 mg IT once on day 1<br />
<br />
*[[Methotrexate (MTX)]] as follows: <br />
**Ages 1 to 1.99: 8 mg IT once per day on days 8 and 29 (CNS 3 also on days 15 and 22)<br />
**Ages 2 to 2.99: 10 mg IT once per day on days 8 and 29 (CNS 3 also on days 15 and 22)<br />
**Ages 3 to 8.99: 12 mg IT once per day on days 8 and 29 (CNS 3 also on days 15 and 22)<br />
**Age 9 and older: 15 mg IT once per day on days 8 and 29 (CNS 3 also on days 15 and 22)<br />
<br />
'''4-week course'''<br />
=====Subsequent treatment=====<br />
<br />
*See protocol for details of treatment beyond induction<br />
<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
===Consolidation===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 - 60 minutes once on days 1 and 29<br />
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup>/day SC or IV over 1 - 30 minutes on days 1 - 4, 8 - 11, 29 - 32, 36 - 39.<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 - 2 hours once on days 15, and 43.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 15, 22, 43, and 50.<br />
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup>/dose PO once per day on days 1 - 14, and 29 - 42.<br />
<br />
======CNS prophylaxis======<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1, 8, 15, and 22.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
DS Arm<br />
<br />
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> x 2 doses PO (given at 48 and 60 hours after the lumbar puncture) on days 3 - 4, 10 - 11, 17 - 18, and 24 - 25.<br />
<br />
'''56-Day Course'''<br />
<br />
====References====<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
===Interim Maintenance with ID MTX===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
=====Chemotherapy=====<br />
<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29, and 43.<br />
*[[Mercaptopurine (6-MP)]] 25 mg/m<sup>2</sup>/dose PO once per day on days 1 - 56.<br />
*Intermediate Dose [[Methotrexate (MTX)]] 2000 mg/m<sup>2</sup> IV over 24 hours on days 1, 15, 29, and 43. <br />
**MTX 200 mg/m<sup>2</sup> IV infused over 30 minutes. This is followed, immediately, by MTX 1800 mg/m<sup>2</sup> given by continuous IV infusion over 23.5 hours.<br />
<br />
ANC must be ≥ 750/µL and platelets must be ≥ 75,000/µL prior to each dose of HD MTX<br />
<br />
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> x a minimum of 5 doses PO or IV (given at 30, 36, 42, 48, and 54 hours after the START of ID MTX infusion) on days 2 - 3, 17 - 18, 31 - 32, and 45 - 46.<br />
<br />
======CNS prophylaxis======<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1 and 29.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
When IT therapy and HD MTX are scheduled for the same day, deliver the IT therapy within 6 hours of the beginning of the IV MTX infusion. (hour -6 or +6, with 0 being the start of the MTX bolus). <br />
<br />
<br />
<br />
'''63-Day Course'''<br />
<br />
====References====<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
===Delayed Intensification===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV push over 1 to 15 minutes once per day on days 1, 8, and 15.<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 to 2 hours once on days 4 and 43.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 43, and 50.<br />
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup> IV or PO twice per day on days 1 - 7 and 15 - 21.<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV over 30 - 60 minutes once on day 29 ONLY.<br />
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup>/day SC or IV over 1 - 30 minutes on days 29 - 32 and 36 - 39.<br />
*[[Thioguanine (Tabloid)]] 60 mg/m<sup>2</sup>/day PO once per day on days 29 to 42.<br />
*[[Folinic acid (Leucovorin)]] 5 mg/m<sup>2</sup> x 2 doses PO or IV (given at 48, and 60 hours after the lumbar puncture) on days 3 - 4, 31 - 32, and 38 - 39.<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1, 29, and 36.<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
<br />
'''56-Day course'''<br />
<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
===DS HR Arm Maintenance===<br />
<br />
====Regimen {{#subobject:98346f|Variant=1}}====<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Randomized portion of RCT<br />
|-<br />
|}<br />
<br />
====Radiotherapy====<br />
For Patients with CNS3 Disease<br />
<br />
*[[External_beam_radiotherapy|Total body irradiation (TBI)]] 1800 cGy in 10 fractions, during the first 4 weeks of Maintenance therapy and should be completed by day 29 of Maintenance.<br />
<br />
====Chemotherapy====<br />
<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/dose PO once per day on days 1 - 84.<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on day 1 ONLY.<br />
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on days 8, 15, 22, (29), 36, 43, 50, 57, 64, 71 and 78. (OMIT DAY 29 WHEN CNS RADIATION IS GIVEN, DUE TO IT MTX).<br />
*[[Prednisone (Sterapred)]] 20 mg/m<sup>2</sup>/dose PO or IV (methylprednisolone given at 80% of the oral dose) twice per day on days 1 - 5.<br />
<br />
=====CNS prophylaxis=====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on day 1 (also Day 29 of cycles 1 and 2, for patients who did NOT receive CNS Radiation).<br />
<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Age<br />
! style="width: 25%" |Dose<br />
|-<br />
|1 - 1.99<br />
|8 mg<br />
|-<br />
|2 - 2.99<br />
|10 mg<br />
|-<br />
|3 - 8.99<br />
|12 mg<br />
|-<br />
|≥ 9<br />
|15 mg<br />
|}<br />
<br />
'''12-Week Cycles repeated until total duration of therapy is 2 years for female patients and 3 years for male patients from the start of interim maintenance.'''<br />
<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
=Prephase=<br />
==Methylprednisolone monotherapy {{#subobject:5gh1bb|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:88fgh7|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1016/s1470-2045(15)00363-0 Place et al. 2015 (DFCI 05-001)]<br />
|2005-2011<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|[https://doi.org/10.1002/pbc.28719 Burns et al. 2020 (DFCI 11-001)]<br />
|2012-2015<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
''Note: Burns et al. 2020 is both an update of DFCI 05-001 and the primary publication of DFCI 11-001.'' <br />
====Chemotherapy====<br />
<br />
*[[Methylprednisolone (Solumedrol)]] 8 mg/m<sup>2</sup> IV three times per day on days 1 to 3<br />
<br />
'''3-day course'''<br />
====Subsequent treatment====<br />
<br />
*DFCI 05-001: Doxorubicin, L-Asparaginase, Methotrexate, Vincristine, Methylprednisolone induction versus [[#Doxorubicin.2C_Methotrexate.2C_Pegaspargase.2C_Vincristine.2C_Methylprednisolone|Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone induction]]<br />
*DFCI 11-001: Calaspargase, Doxorubicin, Methotrexate, Vincristine, Methylprednisolone induction versus [[#Doxorubicin.2C_Methotrexate.2C_Pegaspargase.2C_Vincristine.2C_Methylprednisolone|Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone induction]]<br />
<br />
===References===<br />
<br />
#'''DFCI 05-001:''' Place AE, Stevenson KE, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Supko JG, Asselin BL, Athale UH, Clavell LA, Cole PD, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Welch JJ, Lipshultz SE, Kutok JL, Blonquist TM, Neuberg DS, Sallan SE, Silverman LB. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1677-90. Epub 2015 Nov 6. [https://doi.org/10.1016/s1470-2045(15)00363-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26549586/ PubMed] NCT00400946<br />
##'''Pooled update:''' Burns MA, Place AE, Stevenson KE, Gutiérrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. Epub 2020 Oct 7. Erratum in: Pediatr Blood Cancer. 2021 Mar;68(3):e28885. [https://doi.org/10.1002/pbc.28719 link to original article] '''contains verified protocol in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33026184/ PubMed]<br />
#'''DFCI 11-001:''' Burns MA, Place AE, Stevenson KE, Gutiérrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. Epub 2020 Oct 7. Erratum in: Pediatr Blood Cancer. 2021 Mar;68(3):e28885. [https://doi.org/10.1002/pbc.28719 link to original article] '''contains verified protocol in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33026184/ PubMed] NCT01574274<br />
<br />
==Prednisone monotherapy {{#subobject:8ca13b|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:2fd1d7|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.bloodjournal.org/content/127/17/2101.long Möricke et al. 2016 (AIEOP-BFM ALL 2000)]<br />
|2000-2006<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
====Chemotherapy====<br />
<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 7<br />
<br />
====CNS prophylaxis====<br />
<br />
*[[Methotrexate (MTX)]] 15 mg IT once on day 1<br />
<br />
'''7-day course'''<br />
<br />
====Subsequent treatment====<br />
<br />
*[[#DOLP|Daunorubicin, L-Asparaginase, Vincristine, Prednisone]] versus Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone induction<br />
<br />
===References===<br />
<br />
#'''AIEOP-BFM ALL 2000:''' Möricke A, Zimmermann M, Valsecchi MG, Stanulla M, Biondi A, Mann G, Locatelli F, Cazzaniga G, Niggli F, Aricò M, Bartram CR, Attarbaschi A, Silvestri D, Beier R, Basso G, Ratei R, Kulozik AE, Lo Nigro L, Kremens B, Greiner J, Parasole R, Harbott J, Caruso R, von Stackelberg A, Barisone E, Rössig C, Conter V, Schrappe M. Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. Blood. 2016 Apr 28;127(17):2101-12. Epub 2016 Feb 17. [http://www.bloodjournal.org/content/127/17/2101.long link to original article] '''contains verified protocol in supplement''' [https://pubmed.ncbi.nlm.nih.gov/26888258 PubMed] NCT00430118; NCT00613457<br />
<br />
==Vincristine & Prednisone {{#subobject:663781|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VP: '''<u>V</u>'''incristine & '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:79fc67|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.bloodjournal.org/content/51/3/425.long Sallan et al. 1978]<br />
|1973-1977<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
''Note: this regimen is of historic interest as an induction regimen; it is still occasionally used as pre-phase in patients too ill to get cytotoxic chemotherapy at time of diagnosis.''<br />
====Chemotherapy====<br />
<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO on days 1 to 21<br />
<br />
'''21-day course'''<br />
<br />
===References===<br />
<br />
#Sallan SE, Cammita BM, Cassady JR, Nathan DG, Frei E 3rd. Intermittent combination chemotherapy with adriamycin for childhood acute lymphoblastic leukemia: clinical results. Blood. 1978 Mar;51(3):425-33. [http://www.bloodjournal.org/content/51/3/425.long link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/272207 PubMed]<br />
<br />
=Upfront induction therapy=<br />
==Calaspargase, Daunorubicin, Vincristine, Prednisone {{#subobject:1abca2|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:cf26ce|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239306/ Angiolillo et al. 2014 (COG AALL07P4)]<br />
|2008-2010<br />
| style="background-color:#1a9851" |Randomized (E-RT-switch-ic)<br />
|Daunorubicin, Pegaspargase, Vincristine, Prednisone<br />
| style="background-color:#1a9850" |Longer half-life<br />
|-<br />
|}<br />
====Chemotherapy====<br />
<br />
*[[Calaspargase (Asparlas)]] 2500 units/m<sup>2</sup> IV once on day 4<br />
*[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22<br />
*[[Prednisone (Sterapred)]] 30 mg/m<sup>2</sup> PO twice per day on days 1 to 28<br />
<br />
'''5-week course'''<br />
====Subsequent treatment====<br />
<br />
*See protocol for details of treatment beyond induction<br />
<br />
===References===<br />
<br />
#'''COG AALL07P4:''' Angiolillo AL, Schore RJ, Devidas M, Borowitz MJ, Carroll AJ, Gastier-Foster JM, Heerema NA, Keilani T, Lane AR, Loh ML, Reaman GH, Adamson PC, Wood B, Wood C, Zheng HW, Raetz EA, Winick NJ, Carroll WL, Hunger SP. Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli L-asparaginase in the treatment of patients with acute lymphoblastic leukemia: results from Children's Oncology Group Study AALL07P4. J Clin Oncol. 2014 Dec 1;32(34):3874-82. Epub 2014 Oct 27. [https://doi.org/10.1200/JCO.2014.55.5763 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239306/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/25348002 PubMed] NCT00671034<br />
<br />
==Daunorubicin, Pegaspargase, Vincristine, Dexamethasone {{#subobject:088146|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:98346f|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ Burke et al. 2019 (COG AALL1131)]<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
''Note: the referenced publication does not specifically focus on induction; the full regimen is available as a protocol. Per the protocol, it is intended only for patients less than 10 years old.''<br />
====Chemotherapy====<br />
<br />
*[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV over 1 to 15 minutes once per day on days 1, 8, 15, 22<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV over 1 to 2 hours once on day 4<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22<br />
*[[Dexamethasone (Decadron)]] 5 mg/m<sup>2</sup> IV or PO twice per day on days 1 to 14<br />
<br />
====CNS prophylaxis====<br />
<br />
*[[Cytarabine (Ara-C)]] as follows:<br />
**Ages 1 to 1.99: 30 mg IT once on day 1<br />
**Ages 2 to 2.99: 50 mg IT once on day 1<br />
**Age 3 and older: 70 mg IT once on day 1<br />
*[[Methotrexate (MTX)]] as follows:<br />
**Ages 1 to 1.99: 8 mg IT once per day on days 8 & 29<br />
**Ages 2 to 2.99: 10 mg IT once per day on days 8 & 29<br />
**Ages 3 to 8.99: 12 mg IT once per day on days 8 & 29<br />
**Age 9 and older: 15 mg IT once per day on days 8 & 29<br />
<br />
'''4-week course'''<br />
====Subsequent treatment====<br />
<br />
*See protocol for details of treatment beyond induction<br />
<br />
===References===<br />
<br />
#'''COG AALL1131:''' Burke MJ, Salzer WL, Devidas M, Dai Y, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG. Haematologica. 2019 May;104(5):986-992. Epub 2018 Dec 13. [http://www.haematologica.org/content/104/5/986.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518909/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30545921 PubMed] NCT02883049<br />
<br />
==DOLP {{#subobject:3c9897|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
DOLP: '''<u>D</u>'''aunorubicin, '''<u>O</u>'''ncovin (Vincristine), '''<u>L</u>'''-Asparaginase, '''<u>P</u>'''rednisone<br />
<br>DVPA: '''<u>D</u>'''aunorubicin, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone, '''<u>A</u>'''sparaginase<br />
===Regimen variant #1, 25/6000/1.5/60 {{#subobject:3fe1a2|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2254538/ Seibel et al. 2008 (COG CCG-1961)]<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
''Note: exact days were not specified for the L-asparaginase; suggested days are similar to those used in subsequent parts of the protocol.''<br />
====Chemotherapy====<br />
<br />
*[[Daunorubicin (Cerubidine)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22<br />
*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> IM once per day on days 3, 5, 7, 10, 12, 14, 17, 19, 21<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 28<br />
<br />
====CNS therapy====<br />
<br />
*[[Cytarabine (Ara-C)]] IT once on day 0 (dose not specified)<br />
*[[Methotrexate (MTX)]] IT once per day on days 7 & 28 (dose not specified)<br />
<br />
'''4-week course'''<br />
====Subsequent treatment====<br />
<br />
*Standard versus increased intensity post-remission therapy (see paper for details)<br />
<br />
===Regimen variant #2, 30/5000/1.5/60 ("Phase A" of ALL-BFM 95) {{#subobject:020017|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.bloodjournal.org/content/111/9/4477.long Möricke et al. 2008 (ALL-BFM 95)]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
''Note: see paper for details on dose adjustments based on risk.''<br />
====Chemotherapy====<br />
<br />
*[[Daunorubicin (Cerubidine)]] 30 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22, 29<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 8, 15, 22, 29<br />
*[[Asparaginase (Elspar)]] 5000 units IV over 60 minutes once per day on days 12, 15, 18, 21, 24, 27, 30, 33<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 28<br />
<br />
====CNS therapy====<br />
<br />
*[[Methotrexate (MTX)]] 12 mg IT once per day on days 1, 12, 33<br />
<br />
'''5-week course'''<br />
====Subsequent treatment====<br />
<br />
*See paper for details<br />
<br />
===Regimen variant #3, 30/10,000/1.5/60 ("Protocol I") {{#subobject:0ccc82|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.bloodjournal.org/content/95/11/3310.long Schrappe et al. 2000 (ALL-BFM 90)]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|[https://doi.org/10.1038/sj.leu.2402489 Kamps et al. 2002 (DCLSG ALL-8)]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
''Note: see papers for details on dose adjustments based on risk.''<br />
====Chemotherapy====<br />
<br />
*[[Daunorubicin (Cerubidine)]] 30 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22, 29<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 8, 15, 22, 29<br />
*[[Asparaginase (Elspar)]] 10,000 units IV over 60 minutes once per day on days 12, 15, 18, 21, 24, 27, 30, 33<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 28<br />
<br />
====CNS therapy====<br />
<br />
*[[Methotrexate (MTX)]] 12 mg IT once per day on days 1, 15, 29<br />
<br />
'''5-week course'''<br />
====Subsequent treatment====<br />
<br />
*See papers for details<br />
<br />
===Regimen variant #4, 40/10,000/1.5/60 ("Induction Protocol I" of ALL-BFM 86) {{#subobject:6ad40d|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.bloodjournal.org/content/84/9/3122.long Reiter et al. 1994 (ALL-BFM 86)]<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|[http://www.bloodjournal.org/content/94/4/1226.long Kamps et al. 1999 (DCLSG ALL-7)]<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
====Chemotherapy====<br />
<br />
*[[Daunorubicin (Cerubidine)]] 40 mg/m<sup>2</sup> IV once per day on days 8, 15, 22, 29<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 8, 15, 22, 29<br />
*[[Asparaginase (Elspar)|L-Asparaginase]] 10,000 units/m<sup>2</sup> IV once per day on days 19, 22, 25, 28, 31, 34, 37, 40<br />
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 28<br />
<br />
'''6-week course'''<br />
====Subsequent treatment====<br />
<br />
*Induction phase II (see papers for details)<br />
<br />
===References===<br />
<br />
#'''ALL-BFM 86:''' Reiter A, Schrappe M, Ludwig WD, Hiddemann W, Sauter S, Henze G, Zimmermann M, Lampert F, Havers W, Niethammer D, Odenwald E, Ritter J, Mann G, Welte K, Gadner H, Riehm H. Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients: results and conclusions of the multicenter trial ALL-BFM 86. Blood. 1994 Nov 1;84(9):3122-33. [http://www.bloodjournal.org/content/84/9/3122.long link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/7949185 PubMed]<br />
#'''DCLSG ALL-7:''' Kamps WA, Bökkerink JP, Hählen K, Hermans J, Riehm H, Gadner H, Schrappe M, Slater R, van den Berg-de Ruiter E, Smets LA, de Vaan GA, Weening RS, van Weerden JF, van Wering ER, den der Does-van den Berg A. Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy: results of Dutch Childhood Leukemia Study Group protocol ALL-7 (1988-1991). Blood. 1999 Aug 15;94(4):1226-36. [http://www.bloodjournal.org/content/94/4/1226.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/10438710 PubMed]<br />
#'''ALL-BFM 90:''' Schrappe M, Reiter A, Ludwig WD, Harbott J, Zimmermann M, Hiddemann W, Niemeyer C, Henze G, Feldges A, Zintl F, Kornhuber B, Ritter J, Welte K, Gadner H, Riehm H; German-Austrian-Swiss ALL-BFM Study Group. Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. Blood. 2000 Jun 1;95(11):3310-22. [http://www.bloodjournal.org/content/95/11/3310.long link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/10828010 PubMed]<br />
##'''Pooled subgroup analysis:''' Schrauder A, Reiter A, Gadner H, Niethammer D, Klingebiel T, Kremens B, Peters C, Ebell W, Zimmermann M, Niggli F, Ludwig WD, Riehm H, Welte K, Schrappe M. Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. J Clin Oncol. 2006 Dec 20;24(36):5742-9. [https://doi.org/10.1200/JCO.2006.06.2679 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17179108 PubMed]<br />
#'''DCLSG ALL-8:''' Kamps WA, Bökkerink JP, Hakvoort-Cammel FG, Veerman AJ, Weening RS, van Wering ER, van Weerden JF, Hermans J, Slater R, van den Berg E, Kroes WG, van der Does-van den Berg A. BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8 (1991-1996). Leukemia. 2002 Jun;16(6):1099-111. [https://doi.org/10.1038/sj.leu.2402489 link to original article] '''refers to ALL-BFM 90 protocol''' [https://pubmed.ncbi.nlm.nih.gov/12040440 PubMed]<br />
#'''COG CCG-1961:''' Seibel NL, Steinherz PG, Sather HN, Nachman JB, Delaat C, Ettinger LJ, Freyer DR, Mattano LA Jr, Hastings CA, Rubin CM, Bertolone K, Franklin JL, Heerema NA, Mitchell TL, Pyesmany AF, La MK, Edens C, Gaynon PS. Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2008 Mar 1;111(5):2548-55. [http://www.bloodjournal.org/content/111/5/2548.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2254538/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/18039957 PubMed]<br />
#'''ALL-BFM 95:''' Möricke A, Reiter A, Zimmermann M, Gadner H, Stanulla M, Dördelmann M, Löning L, Beier R, Ludwig WD, Ratei R, Harbott J, Boos J, Mann G, Niggli F, Feldges A, Henze G, Welte K, Beck JD, Klingebiel T, Niemeyer C, Zintl F, Bode U, Urban C, Wehinger H, Niethammer D, Riehm H, Schrappe M; German-Austrian-Swiss ALL-BFM Study Group. Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95. Blood. 2008 May 1;111(9):4477-89. Epub 2008 Feb 19. Erratum in: Blood. 2009 Apr 30;113(18):4478. Dosage error in article text. [http://www.bloodjournal.org/content/111/9/4477.long link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/18285545 PubMed]<br />
##'''Pooled subgroup analysis:''' Schrauder A, Reiter A, Gadner H, Niethammer D, Klingebiel T, Kremens B, Peters C, Ebell W, Zimmermann M, Niggli F, Ludwig WD, Riehm H, Welte K, Schrappe M. Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. J Clin Oncol. 2006 Dec 20;24(36):5742-9. [https://doi.org/10.1200/JCO.2006.06.2679 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17179108 PubMed]<br />
<br />
==DOLP (Prednisolone) {{#subobject:3c7jg7|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
DOLP: '''<u>D</u>'''aunorubicin, '''<u>O</u>'''ncovin (Vincristine), '''<u>L</u>'''-Asparaginase, '''<u>P</u>'''rednisolone<br />
===Regimen variant #1, 30/10,000/1.5/60 {{#subobject:087cg2|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904579/ de Moerloose et al. 2010 (EORTC CLG 58951)]<br />
|1999-2002<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Daunorubicin, L-Asparaginase, Vincristine, Dexamethasone<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS<br />
|-<br />
|}<br />
''Note: see paper for details on CNS therapy and dose adjustments based on risk; these instructions include a 7-day pre-phase and are for AR1 patients.''<br />
====Chemotherapy====<br />
<br />
*[[Daunorubicin (Cerubidine)]] 30 mg/m<sup>2</sup> IV once per day on days 8, 15, 22, 29<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 8, 15, 22, 29<br />
*[[Asparaginase (Elspar)]] 10,000 units (route not specified) once per day on days 12, 15, 18, 22, 25, 29, 32, 35<br />
*[[Prednisolone (Millipred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 28, then tapered over 9 days<br />
<br />
'''5-week course'''<br />
====Subsequent treatment====<br />
<br />
*See paper for details<br />
<br />
===Regimen variant #2, 45/6000/1.5/40 {{#subobject:b39731|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.thelancet.com/journals/lancet/article/PII014067369292103M/fulltext Chessells et al. 1992 (UK MRC ALLX)]<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
''Note: exact days for L-asparaginase were not specified in the protocol.''<br />
====Chemotherapy====<br />
<br />
*[[Daunorubicin (Cerubidine)]] 45 mg/m<sup>2</sup> IV once per day on days 1 & 2<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29<br />
*[[Asparaginase (Elspar)]] 6000 units/m<sup>2</sup> SC once per day on days 3, 5, 7, 10, 12, 14, 17, 19, 21<br />
*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup>/day PO on days 1 to 28<br />
<br />
'''29-day course'''<br />
====Subsequent treatment====<br />
<br />
*Intensification (randomized) or Cy/TBI with allo HSCT, depending on donor availability<br />
<br />
===References===<br />
<br />
#'''UK MRC ALLX:''' Chessells JM, Bailey C, Wheeler K, Richards SM. Bone marrow transplantation for high-risk childhood lymphoblastic leukaemia in first remission: experience in MRC UKALL X. Lancet. 1992 Sep 5;340(8819):565-8. [https://www.thelancet.com/journals/lancet/article/PII014067369292103M/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/1355153 PubMed]<br />
##'''Update:''' Chessells JM, Bailey C, Richards SM; Medical Research Council Working Party on Childhood Leukaemia. Intensification of treatment and survival in all children with lymphoblastic leukaemia: results of UK Medical Research Council trial UKALL X. Lancet. 1995 Jan 21;345(8943):143-8. [https://www.thelancet.com/journals/lancet/article/PIIS0140673695901647/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/7823668 PubMed]<br />
#'''EORTC CLG 58951:''' De Moerloose B, Suciu S, Bertrand Y, Mazingue F, Robert A, Uyttebroeck A, Yakouben K, Ferster A, Margueritte G, Lutz P, Munzer M, Sirvent N, Norton L, Boutard P, Plantaz D, Millot F, Philippet P, Baila L, Benoit Y, Otten J; Children's Leukemia Group of the European Organisation for Research and Treatment of Cancer. Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951. Blood. 2010 Jul 8;116(1):36-44. Epub 2010 Apr 20. [http://www.bloodjournal.org/content/116/1/36.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904579/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20407035 PubMed] NCT00003728<br />
##'''Update:''' Domenech C, Suciu S, De Moerloose B, Mazingue F, Plat G, Ferster A, Uyttebroeck A, Sirvent N, Lutz P, Yakouben K, Munzer M, Röhrlich P, Plantaz D, Millot F, Philippet P, Dastugue N, Girard S, Cavé H, Benoit Y, Bertrand Y; Children's Leukemia Group (CLG) of European Organisation for Research and Treatment of Cancer. Dexamethasone (6 mg/m<sup>2</sup>/day) and prednisolone (60 mg/m<sup>2</sup>/day) were equally effective as induction therapy for childhood acute lymphoblastic leukemia in the EORTC CLG 58951 randomized trial. Haematologica. 2014 Jul;99(7):1220-7. Epub 2014 Apr 11. [http://www.haematologica.org/content/99/7/1220.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077084/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24727815 PubMed]<br />
##'''Update:''' Mondelaers V, Suciu S, De Moerloose B, Ferster A, Mazingue F, Plat G, Yakouben K, Uyttebroeck A, Lutz P, Costa V, Sirvent N, Plouvier E, Munzer M, Poirée M, Minckes O, Millot F, Plantaz D, Maes P, Hoyoux C, Cavé H, Rohrlich P, Bertrand Y, Benoit Y; Children–s Leukemia Group (CLG) of the European Organisation for Research and Treatment of Cancer. Prolonged versus standard native E coli asparaginase therapy in childhood acute lymphoblastic leukemia and non-Hodgkin lymphoma: final results of the EORTC-CLG randomized phase III trial 58951. Haematologica. 2017 Oct;102(10):1727-1738. Epub 2017 Jul 27. [http://www.haematologica.org/content/102/10/1727.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622857/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28751566 PubMed]<br />
<br />
==Doxorubicin, Mercaptopurine, Pegaspargase, Vincristine, Prednisolone {{#subobject:127ca2|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:nc303e|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.18.01877 Albertsen et al. 2019 (NOPHO ALL2008)]<br />
|2008-2016<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
''See protocol for initiation dependencies of 6-MP and pegaspargase.''<br />
====Chemotherapy====<br />
<br />
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 & 22<br />
*[[Mercaptopurine (6-MP)]] 25 mg/m<sup>2</sup> PO once per day on days 30 to 35<br />
*[[Pegaspargase (Oncaspar)]] 1000 units/m<sup>2</sup> IM once on day 30<br />
*[[Vincristine (Oncovin)]] as follows:<br />
**Younger than 18: 2 mg/m<sup>2</sup> (maximum dose of 2.5 mg) IV once per day on days 1, 8, 15, 22, 29<br />
**18 or older: 2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22, 29<br />
*[[Prednisolone (Millipred)]] 20 mg/m<sup>2</sup> PO three times per day on days 1 to 29, then 10 mg/m<sup>2</sup> PO three times per day on days 30 to 32, then 5 mg/m<sup>2</sup> PO three times per day on days 33 to 35, then 2.5 mg/m<sup>2</sup> PO three times per day on days 36 to 38<br />
<br />
====CNS prophylaxis====<br />
<br />
*[[Methotrexate (MTX)]] as follows:<br />
**Ages 1 to 1.9: 8 mg IT once per day on days 1, 8, 15, 29<br />
**Ages 2 to 2.9: 10 mg IT once per day on days 1, 8, 15, 29<br />
**Age 3 and older: 12 mg IT once per day on days 1, 8, 15, 29<br />
<br />
'''5-week course'''<br />
====Subsequent treatment====<br />
<br />
*See protocol for details of treatment beyond induction<br />
<br />
===References===<br />
<br />
#'''NOPHO ALL2008:''' Albertsen BK, Grell K, Abrahamsson J, Lund B, Vettenranta K, Jónsson ÓG, Frandsen TL, Wolthers BO, Heyman M, Schmiegelow K. Intermittent versus continuous PEG-asparaginase to reduce asparaginase-associated toxicities: a NOPHO ALL2008 randomized study. J Clin Oncol. 2019 Jul 1;37(19):1638-1646. Epub 2019 Apr 12. [https://doi.org/10.1200/JCO.18.01877 link to original article] '''contains verified protocol in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30978155 PubMed] NCT00819351<br />
<br />
==Doxorubicin, Methotrexate, Pegaspargase, Vincristine, Methylprednisolone {{#subobject:h1gtbb|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:hgu1h7|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 17%" |Study<br />
! style="width: 15%" |Years of enrollment<br />
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 17%" |Comparator<br />
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]<br />
|-<br />
|[https://doi.org/10.1016/s1470-2045(15)00363-0 Place et al. 2015 (DFCI 05-001)]<br />
|2005-2011<br />
| style="background-color:#1a9851" |Phase III (E-switch-ic)<br />
|Doxorubicin, L-Asparaginase, Methotrexate, Vincristine, Methylprednisolone<br />
| style="background-color:#ffffbf" |Did not meet secondary endpoint of DFS<br />
| style="background-color:#1a9850" |Less anxiety<br />
|-<br />
|[https://doi.org/10.1002/pbc.28719 Burns et al. 2020 (DFCI 11-001)]<br />
|2012-2015<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Calaspargase, Doxorubicin, Methotrexate, Vincristine, Methylprednisolone<br />
| style="background-color:#d3d3d3" |Not reported<br />
|<br />
|-<br />
|}<br />
''Note: Burns et al. 2020 is both an update of DFCI 05-001 and the primary publication of DFCI 11-001. Day numbering takes into account the pre-phase.''<br />
====Preceding treatment====<br />
<br />
*[[#Methylprednisolone_monotherapy|Methylprednisolone pre-phase]]<br />
<br />
====Chemotherapy====<br />
<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 4 & 5<br />
*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once on day 6<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV once on day 7<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 4, 11, 18, 25<br />
*[[Methylprednisolone (Solumedrol)]] 8 mg/m<sup>2</sup> IV three times per day on days 4 to 32<br />
<br />
====Supportive medications====<br />
<br />
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 4 & 5<br />
<br />
'''28-day course'''<br />
====CNS prophylaxis====<br />
<br />
*[[Cytarabine (Ara-C)]] IT once per day on days 1 & 18<br />
**Day 18 dose is admixed with MTX and HC<br />
*[[Methotrexate (MTX)]] IT once per day on days 18 & 32<br />
**Day 18 dose is admixed with Ara-C and HC<br />
*[[Hydrocortisone (Cortef)]] IT once on day 18, admixed with Ara-C and MTX<br />
<br />
====Subsequent treatment====<br />
<br />
*[[#Doxorubicin.2C_Mercaptopurine.2C_Methotrexate.2C_Vincristin|Doxorubicin, Mercaptopurine, Methotrexate, Vincristine consolidation (IA)]]<br />
<br />
===References===<br />
<br />
#'''DFCI 05-001:''' Place AE, Stevenson KE, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Supko JG, Asselin BL, Athale UH, Clavell LA, Cole PD, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Welch JJ, Lipshultz SE, Kutok JL, Blonquist TM, Neuberg DS, Sallan SE, Silverman LB. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1677-90. Epub 2015 Nov 6. [https://doi.org/10.1016/s1470-2045(15)00363-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26549586/ PubMed] NCT00400946<br />
##'''Pooled update:''' Burns MA, Place AE, Stevenson KE, Gutiérrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. Epub 2020 Oct 7. Erratum in: Pediatr Blood Cancer. 2021 Mar;68(3):e28885. [https://doi.org/10.1002/pbc.28719 link to original article] '''contains verified protocol in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33026184/ PubMed]<br />
#'''DFCI 11-001:''' Burns MA, Place AE, Stevenson KE, Gutiérrez A, Forrest S, Pikman Y, Vrooman LM, Harris MH, Hunt SK, O'Brien JE, Asselin BL, Athale UH, Clavell LA, Cole PD, Gennarini LM, Kahn JM, Kelly KM, Laverdiere C, Leclerc JM, Michon B, Schorin MA, Sulis ML, Welch JJG, Neuberg DS, Sallan SE, Silverman LB. Identification of prognostic factors in childhood T-cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05-001 and 11-001. Pediatr Blood Cancer. 2021 Jan;68(1):e28719. Epub 2020 Oct 7. Erratum in: Pediatr Blood Cancer. 2021 Mar;68(3):e28885. [https://doi.org/10.1002/pbc.28719 link to original article] '''contains verified protocol in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33026184/ PubMed] NCT01574274<br />
<br />
==Pegaspargase, Vincristine, Dexamethasone {{#subobject:15hgu1|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:e8uyt1|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030893/ Maloney et al. 2019 (COG AALL0331)]<br />
|2005-2010<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
''Note: there are very minor differences in timing between protocols; see papers for details.''<br />
====Chemotherapy====<br />
<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV once on day 4<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22<br />
*[[Dexamethasone (Decadron)]] 3 mg/m<sup>2</sup> PO twice per day on days 1 to 28<br />
<br />
====CNS prophylaxis====<br />
<br />
*[[Cytarabine (Ara-C)]] IT once at some point between days -2 and 1<br />
*[[Methotrexate (MTX)]] IT once per day on days 8 & 29<br />
<br />
'''35-day course'''<br />
====Subsequent treatment====<br />
<br />
*COG AALL0331, M2 marrow or M1 marrow with MRD of at least 1% at day 29: Extended induction<br />
*COG AALL0932: [[#Mercaptopurine_.26_Vincristine|6-MP & Vincristine consolidation]]<br />
<br />
===References===<br />
<br />
#'''COG AALL0331:''' Maloney KW, Devidas M, Wang C, Mattano LA, Friedmann AM, Buckley P, Borowitz MJ, Carroll AJ, Gastier-Foster JM, Heerema NA, Kadan-Lottick N, Loh ML, Matloub YH, Marshall DT, Stork LC, Raetz EA, Wood B, Hunger SP, Carroll WL, Winick NJ. Outcome in Children With Standard-Risk B-Cell Acute Lymphoblastic Leukemia: Results of Children's Oncology Group Trial AALL0331. J Clin Oncol. 2020 Feb 20;38(6):602-612. Epub 2019 Dec 11. [https://doi.org/10.1200/jco.19.01086 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7030893/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/31825704/ PubMed] NCT00103285<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
==Pegaspargase, Vincristine, Prednisone {{#subobject:158722|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:e8uhb3|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[http://www.bloodjournal.org/content/99/6/1986.long Avramis et al. 2002 (CCG 1962)]<br />
|1997-1998<br />
| style="background-color:#1a9851" |Randomized (E-RT-switch-ic)<br />
|L-Asparaginase, Vincristine, Prednisone<br />
| style="background-color:#ffffbf" |Did not meet secondary endpoint of EFS<br />
|-<br />
|}<br />
''Note: the primary endpoint of CCG 1962 was incidence of high-titer ASNase antibodies in the first dose intensification, which is neither an efficacy nor a toxicity endpoint.''<br />
====Chemotherapy====<br />
<br />
*[[Pegaspargase (Oncaspar)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Prednisone (Sterapred)]]<br />
<br />
====Subsequent treatment====<br />
<br />
*See protocol for details of treatment beyond induction<br />
<br />
===References===<br />
<br />
#'''CCG 1962:''' Avramis VI, Sencer S, Periclou AP, Sather H, Bostrom BC, Cohen LJ, Ettinger AG, Ettinger LJ, Franklin J, Gaynon PS, Hilden JM, Lange B, Majlessipour F, Mathew P, Needle M, Neglia J, Reaman G, Holcenberg JS, Stork L. A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children's Cancer Group study. Blood. 2002 Mar 15;99(6):1986-94. Erratum in: Blood 2002 Sep 1;100(5):1531. [http://www.bloodjournal.org/content/99/6/1986.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/11877270 PubMed]<br />
<br />
=Early intensification therapy=<br />
==Cyclophosphamide, Etoposide, Methotrexate {{#subobject:6ahzn6|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:16fxc9|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5145261/ Dreyer et al. 2014 (COG P9407)]<br />
|2001-2006<br />
| style="background-color:#91cf61" |Non-randomized<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://doi.org/10.1038/s41375-021-01177-6 Brown et al. 2021 (COG AALL0631)]<br />
|2008-2014<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Cyclophosphamide, Etoposide, Lestaurtinib, Methotrexate<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS<br />
|-<br />
|}<br />
====Biomarker eligibility criteria====<br />
<br />
*COG AALL0631: KMT2A rearrangement<br />
<br />
====Preceding treatment====<br />
<br />
*Induction<br />
<br />
====Chemotherapy====<br />
<br />
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV over 30 minutes once per day on days 15 to 19<br />
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 15 to 19<br />
*[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV over 20 minutes, then 3800 mg/m<sup>2</sup> IV continuous infusion over 23 hours and 40 minutes on days 1 & 8 (total dose: 8000 mg/m<sup>2</sup>)<br />
<br />
====Subsequent treatment====<br />
<br />
*Reinduction<br />
<br />
===References===<br />
<br />
#'''COG P9407:''' Dreyer ZE, Hilden JM, Jones TL, Devidas M, Winick NJ, Willman CL, Harvey RC, Chen IM, Behm FG, Pullen J, Wood BL, Carroll AJ, Heerema NA, Felix CA, Robinson B, Reaman GH, Salzer WL, Hunger SP, Carroll WL, Camitta BM. Intensified chemotherapy without SCT in infant ALL: results from COG P9407 (Cohort 3). Pediatr Blood Cancer. 2015 Mar;62(3):419-26. Epub 2014 Nov 14. [https://doi.org/10.1002/pbc.25322 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5145261/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25399948/ PubMed] NCT00002756<br />
#'''COG AALL0631:''' Brown PA, Kairalla JA, Hilden JM, Dreyer ZE, Carroll AJ, Heerema NA, Wang C, Devidas M, Gore L, Salzer WL, Winick NJ, Carroll WL, Raetz EA, Borowitz MJ, Small D, Loh ML, Hunger SP. FLT3 inhibitor lestaurtinib plus chemotherapy for newly diagnosed KMT2A-rearranged infant acute lymphoblastic leukemia: Children's Oncology Group trial AALL0631. Leukemia. 2021 May;35(5):1279-1290. Epub 2021 Feb 23. Erratum in: Leukemia. 2021 Apr 12. [https://doi.org/10.1038/s41375-021-01177-6 link to original article] '''contains verified protocol in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33623141/ PubMed] NCT00557193<br />
<br />
==Mercaptopurine & Methotrexate {{#subobject:6ad6d6|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:5b0ec9|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.1998.16.1.246 Mahoney et al. 1998 (POG 9005)]<br />
|1991-1993<br />
| style="background-color:#1a9851" |Phase III (E-switch-ic)<br />
|LDMTX/IVMP<br />
| style="background-color:#91cf60" |Seems to have superior CCR<br />
|-<br />
|[https://www.nature.com/articles/2402132 Lauer et al. 2001 (POG 9006)]<br />
|1991-1994<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Intensive chemotherapy<br />
| style="background-color:#fee08b" |Might have inferior EFS<br />
|-<br />
|}<br />
====Preceding treatment====<br />
<br />
*POG 9006: [[#DOLP|DOLP induction]]<br />
<br />
====Chemotherapy====<br />
<br />
*[[Mercaptopurine (6-MP)]]<br />
*[[Methotrexate (MTX)]]<br />
<br />
====Subsequent treatment====<br />
<br />
*POG 9006: [[#Mercaptopurine_.26_Methotrexate_2|6-MP & MTX maintenance]]<br />
<br />
===References===<br />
<br />
#'''POG 9005:''' Mahoney DH Jr, Shuster J, Nitschke R, Lauer SJ, Winick N, Steuber CP, Camitta B. Intermediate-dose intravenous methotrexate with intravenous mercaptopurine is superior to repetitive low-dose oral methotrexate with intravenous mercaptopurine for children with lower-risk B-lineage acute lymphoblastic leukemia: a Pediatric Oncology Group phase III trial. J Clin Oncol. 1998 Jan;16(1):246-54. [https://doi.org/10.1200/JCO.1998.16.1.246 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9440749 PubMed]<br />
#'''POG 9006:''' Lauer SJ, Shuster JJ, Mahoney DH Jr, Winick N, Toledano S, Munoz L, Kiefer G, Pullen JD, Steuber CP, Camitta BM. A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group phase III randomized trial. Leukemia. 2001 Jul;15(7):1038-45. [https://www.nature.com/articles/2402132 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11455971 PubMed]<br />
<br />
=Consolidation after upfront therapy (including post-remission therapy)=<br />
''Note that many of these regimens are complex and as such will be referred to by their study name, not by the individual drug names. This is also a phase of treatment often referred to as post-remission or postinduction therapy.''<br />
==AALL0232 consolidation {{#subobject:065gg9|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:342b6d|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 50%" |Study<br />
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981974/ Larsen et al. 2016 (COG AALL0232)]<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
====Chemotherapy====<br />
<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 29<br />
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup> IV or SC once per day on days 1 to 4, 8 to 11, 29 to 32, 36 to 39<br />
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 14, 29 to 42<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IM or IV once per day on days 15 & 43<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 15, 22, 43, 50<br />
<br />
'''50-day course'''<br />
====Subsequent treatment====<br />
<br />
*6-MP, Capizzi MTX, Pegaspargase, Vincristine interim maintenance versus [[#Mercaptopurine.2C_Methotrexate.2C_Vincristine_2|6-MP, HD-MTX, Vincristine interim maintenance]]<br />
<br />
===References===<br />
<br />
#'''COG AALL0232:''' Larsen EC, Devidas M, Chen S, Salzer WL, Raetz EA, Loh ML, Mattano LA Jr, Cole C, Eicher A, Haugan M, Sorenson M, Heerema NA, Carroll AA, Gastier-Foster JM, Borowitz MJ, Wood BL, Willman CL, Winick NJ, Hunger SP, Carroll WL. Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: a report from Children's Oncology Group study AALL0232. J Clin Oncol. 2016 Jul 10;34(20):2380-8. Epub 2016 Apr 25. [https://doi.org/10.1200/JCO.2015.62.4544 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981974/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/27114587 PubMed] NCT00075725<br />
<br />
==Augmented BFM consolidation {{#subobject:065ff9|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:687b6d|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.nejm.org/doi/full/10.1056/NEJM199806043382304 Nachman et al. 1998]<br />
|1991-1995<br />
| style="background-color:#1a9851" |Phase III (E-esc)<br />
|Standard BFM consolidation<br />
| style="background-color:#91cf60" |Seems to have superior OS<br />
|-<br />
|}<br />
''Unlikely to be completed, but of historic interest.''<br />
====Chemotherapy====<br />
<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
*[[Cytarabine (Ara-C)]]<br />
*[[Asparaginase (Elspar)]]<br />
*[[Mercaptopurine (6-MP)]]<br />
*[[Vincristine (Oncovin)]]<br />
<br />
===References===<br />
<br />
#Nachman JB, Sather HN, Sensel MG, Trigg ME, Cherlow JM, Lukens JN, Wolff L, Uckun FM, Gaynon PS. Augmented post-induction therapy for children with high-risk acute lymphoblastic leukemia and a slow response to initial therapy. N Engl J Med. 1998 Jun 4;338(23):1663-71. [https://www.nejm.org/doi/full/10.1056/NEJM199806043382304 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9614257 PubMed]<br />
<br />
==Cyclophosphamide & TBI, then allo HSCT {{#subobject:a9f7e8|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation<br />
===Regimen {{#subobject:6ca28d|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.bloodjournal.org/content/54/2/468.long Thomas et al. 1979]<br />
|1976-1977<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
{{#lst:Allogeneic HSCT|6ca28d}}<br />
====Immunotherapy====<br />
<br />
*[[Allogeneic stem cells]]<br />
<br />
'''Stem cells transfused on day 0'''<br />
===References===<br />
<br />
#Thomas ED, Sanders JE, Flournoy N, Johnson FL, Buckner CD, Clift RA, Fefer A, Goodell BW, Storb R, Weiden PL. Marrow transplantation for patients with acute lymphoblastic leukemia in remission. Blood. 1979 Aug;54(2):468-76. [http://www.bloodjournal.org/content/54/2/468.long link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/378292 PubMed]<br />
<br />
==Etoposide & TBI, then allo HSCT {{#subobject:b389e1|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:45f841|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.thelancet.com/journals/lancet/article/PIIS014067360566998X/fulltext Balduzzi et al. 2005]<br />
|1995-2000<br />
| style="background-color:#1a9851" |Quasi-randomized<br />
|Chemotherapy<br />
| style="background-color:#91cf60" |Seems to have superior DFS<br />
|-<br />
|[https://doi.org/10.1200/jco.2014.58.9747 Peters et al. 2015 (ALL-SCT-BFM 2003)]<br />
|2003-2011<br />
| style="background-color:#91cf61" |Non-randomized<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|}<br />
{{#lst:Allogeneic HSCT|45f841}}<br />
====Immunotherapy====<br />
<br />
*[[Allogeneic stem cells]]<br />
<br />
'''Stem cells transfused on day 0'''<br />
===References===<br />
<br />
#Balduzzi A, Valsecchi MG, Uderzo C, De Lorenzo P, Klingebiel T, Peters C, Stary J, Felice MS, Magyarosy E, Conter V, Reiter A, Messina C, Gadner H, Schrappe M. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet. 2005 Aug 20-26;366(9486):635-42. [https://www.thelancet.com/journals/lancet/article/PIIS014067360566998X/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/16112299 PubMed]<br />
#'''ALL-SCT-BFM-2003:''' Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, Lang P, Sykora KW, Schrum J, Kremens B, Ehlert K, Albert MH, Meisel R, Matthes-Martin S, Gungor T, Holter W, Strahm B, Gruhn B, Schulz A, Woessmann W, Poetschger U, Zimmermann M, Klingebiel T. Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors-the ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015 Apr 10;33(11):1265-74. Epub 2015 Mar 9. [https://doi.org/10.1200/jco.2014.58.9747 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25753432 PubMed]<br />
<br />
==Mercaptopurine & Vincristine {{#subobject:171gc1|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:1ygvt1|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
====Preceding treatment====<br />
<br />
*[[#Pegaspargase.2C_Vincristine.2C_Dexamethasone|Pegaspargase, Vincristine, Dexamethasone induction]]<br />
<br />
====Chemotherapy====<br />
<br />
*[[Mercaptopurine (6-MP)]] 75 mg/m<sup>2</sup>/day PO on days 1 to 28<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1<br />
<br />
====CNS prophylaxis====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1, 8, 15<br />
<br />
'''28-day course'''<br />
====Subsequent treatment====<br />
<br />
*[[#Methotrexate_.26_Vincristine|MTX & Vincristine interim maintenance]]<br />
<br />
===References===<br />
<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
=Interim maintenance=<br />
==Mercaptopurine, Methotrexate, Vincristine {{#subobject:72025a|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:b9e09c|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981974/ Larsen et al. 2016 (COG AALL0232)]<br />
|2004-2011<br />
| style="background-color:#1a9851" |Phase III (E-switch-ic)<br />
|Mercaptopurine, Capizzi MTX, Pegaspargase, Vincristine<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
<br />
*[[Mercaptopurine (6-MP)]] 25 mg/m<sup>2</sup> PO once per day on days 1 to 56<br />
*[[Methotrexate (MTX)]] 5000 mg/m<sup>2</sup> IV once per day on days 1, 15, 29, 43<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 15, 29, 43<br />
<br />
====Intrathecal component====<br />
<br />
*[[Methotrexate (MTX)]] once per day on days 1 & 29<br />
<br />
===References===<br />
<br />
#'''COG AALL0232:''' Larsen EC, Devidas M, Chen S, Salzer WL, Raetz EA, Loh ML, Mattano LA Jr, Cole C, Eicher A, Haugan M, Sorenson M, Heerema NA, Carroll AA, Gastier-Foster JM, Borowitz MJ, Wood BL, Willman CL, Winick NJ, Hunger SP, Carroll WL. Dexamethasone and high-dose methotrexate improve outcome for children and young adults with high-risk B-acute lymphoblastic leukemia: a report from Children's Oncology Group study AALL0232. J Clin Oncol. 2016 Jul 10;34(20):2380-8. Epub 2016 Apr 25. [https://doi.org/10.1200/JCO.2015.62.4544 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981974/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/27114587 PubMed] NCT00075725<br />
<br />
==Methotrexate & Vincristine {{#subobject:0ae09f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:57f39d|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ Matloub et al. 2011 (COG CCG-1991)]<br />
|2000-2005<br />
| style="background-color:#1a9851" |Phase III (E-de-esc)<br />
|Mercaptopurine, MTX, Vincristine, Dexamethasone<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|}<br />
====Preceding treatment====<br />
<br />
*COG AALL0932: [[#Mercaptopurine_.26_Vincristine|6-MP & Vincristine consolidation]]<br />
<br />
====Chemotherapy====<br />
<br />
*[[Methotrexate (MTX)]] 100 mg/m<sup>2</sup> IV once on day 1, then 150 mg/m<sup>2</sup> IV once on day 11, then 200 mg/m<sup>2</sup> IV once on day 21, then 250 mg/m<sup>2</sup> IV once on day 31, then 300 mg/m<sup>2</sup> IV once on day 41<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41<br />
<br />
====CNS prophylaxis====<br />
<br />
*[[Methotrexate (MTX)]] IT once on day 31<br />
<br />
'''8-week course'''<br />
====Subsequent treatment====<br />
<br />
*COG AALL0932: [[#AALL0932_delayed_intensification|AALL0932 delayed intensification]]<br />
<br />
===References===<br />
<br />
#'''COG CCG-1991:''' Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. Epub 2011 May 11. [http://www.bloodjournal.org/content/118/2/243.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138679/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21562038 PubMed] NCT00005945<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
=Delayed intensification=<br />
<br />
==AALL0932 delayed intensification {{#subobject:17185g|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:1y47gc|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
====Preceding treatment====<br />
<br />
*[[#Methotrexate_.26_Vincristine|MTX & Vincristine interim maintenance]]<br />
<br />
====Chemotherapy====<br />
<br />
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 29<br />
*[[Cytarabine (Ara-C)]] 75 mg/m<sup>2</sup>/day SC or IV on days 29 to 32, 36 to 39<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IV once on day 4<br />
*[[Thioguanine (Tabloid)]] 60 mg/m<sup>2</sup>/day PO on days 29 to 42<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15<br />
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup>/day PO on days 1 to 7, 15 to 21<br />
<br />
====CNS prophylaxis====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1 & 29<br />
<br />
'''8-week course'''<br />
====Subsequent treatment====<br />
<br />
*[[#Methotrexate_.26_Vincristine_2|MTX & Vincristine interim maintenance II]]<br />
<br />
===References===<br />
<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
=Interim maintenance II=<br />
==Methotrexate & Vincristine {{#subobject:ajbz5g|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:18guaz|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/jco.20.00494 Angiolillo et al. 2021 (COG AALL0932)]<br />
|2010-2018<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
|-<br />
|}<br />
''Note: starting dose of the systemic MTX is 2/3 of the MTD from interim maintenance I; dosage below assumes that the final maximum dose was tolerated.''<br />
====Preceding treatment====<br />
<br />
*[[#AALL0932_delayed_intensification|AALL0932 delayed intensification]]<br />
<br />
====Chemotherapy====<br />
<br />
*[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV once on day 1, then 250 mg/m<sup>2</sup> IV once on day 11, then 300 mg/m<sup>2</sup> IV once on day 21, then 350 mg/m<sup>2</sup> IV once on day 31, then 400 mg/m<sup>2</sup> IV once on day 41<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 11, 21, 31, 41<br />
<br />
====CNS prophylaxis====<br />
<br />
*[[Methotrexate (MTX)]] IT once per day on days 1 & 31<br />
<br />
'''8-week course'''<br />
====Subsequent treatment====<br />
<br />
*Randomization to one of four maintenance arms; see paper for details.<br />
<br />
===References===<br />
<br />
#'''COG AALL0932:''' Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. Epub 2021 Jan 7. [https://doi.org/10.1200/jco.20.00494 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33411585/ PubMed] NCT01190930<br />
<br />
=Maintenance after upfront therapy=<br />
==Mercaptopurine & Methotrexate {{#subobject:6366a6|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:e46d92|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2001.19.7.1935 Millot et al. 2001 (EORTC 58881)]<br />
|1990-1996<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|[[#Mercaptopurine_.26_Methotrexate_2|6-MP & MTX]]; IV 6-MP & PO MTX<br />
| style="background-color:#1a9850" |Superior DFS<sup>1</sup><br />
|-<br />
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(07)60073-7/fulltext Conter et al. 2007 (I-BFM-SG IR ALL)]<br />
|1995-2000<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|D-OMP<br />
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS<br />
|-<br />
|}<br />
''<sup>1</sup>Reported efficacy for EORTC 58881 is based on the 2005 update.''<br />
====Preceding treatment====<br />
<br />
*I-BFM-SG IR ALL: BFM re-induction<br />
<br />
====Chemotherapy====<br />
<br />
*[[Mercaptopurine (6-MP)]] 50 mg/m<sup>2</sup> PO once per day<br />
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once on day 1<br />
<br />
'''7-day cycle for 74 cycles or a total of 2 years from start of treatment'''<br />
<br />
===References===<br />
<br />
#'''EORTC 58881:''' Millot F, Suciu S, Philippe N, Benoit Y, Mazingue F, Uyttebroeck A, Lutz P, Mechinaud F, Robert A, Boutard P, Marguerite G, Ferster A, Plouvier E, Rialland X, Behard C, Plantaz D, Dresse MF, Philippet P, Norton L, Thyss A, Dastugue N, Waterkeyn C, Vilmer E, Otten J; Children's Leukemia Cooperative Group of the European Organiztaion for Research and Treatment of Cancer. Value of high-dose cytarabine during interval therapy of a Berlin-Frankfurt-Munster-based protocol in increased-risk children with acute lymphoblastic leukemia and lymphoblastic lymphoma: results of the European Organisation for Research and Treatment of Cancer 58881 randomized phase III trial. J Clin Oncol. 2001 Apr 1;19(7):1935-42. [https://doi.org/10.1200/JCO.2001.19.7.1935 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11283125 PubMed]<br />
##'''Update:''' Duval M, Suciu S, Ferster A, Rialland X, Nelken B, Lutz P, Benoit Y, Robert A, Manel AM, Vilmer E, Otten J, Philippe N. Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer-Children's Leukemia Group phase 3 trial. Blood. 2002 Apr 15;99(8):2734-9. [http://www.bloodjournal.org/content/99/8/2734.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/11929760 PubMed]<br />
##'''Update:''' van der Werff Ten Bosch J, Suciu S, Thyss A, Bertrand Y, Norton L, Mazingue F, Uyttebroeck A, Lutz P, Robert A, Boutard P, Ferster A, Plouvier E, Maes P, Munzer M, Plantaz D, Dresse MF, Philippet P, Sirvent N, Waterkeyn C, Vilmer E, Philippe N, Otten J. Value of intravenous 6-mercaptopurine during continuation treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma: final results of a randomized phase III trial (58881) of the EORTC CLG. Leukemia. 2005 May;19(5):721-6. [https://www.nature.com/articles/2403689 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15744348 PubMed]<br />
#'''I-BFM-SG IR ALL:''' Conter V, Valsecchi MG, Silvestri D, Campbell M, Dibar E, Magyarosy E, Gadner H, Stary J, Benoit Y, Zimmermann M, Reiter A, Riehm H, Masera G, Schrappe M. Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leukaemia: a multicentre randomised trial. Lancet. 2007 Jan 13;369(9556):123-31. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(07)60073-7/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/17223475 PubMed] NCT00411541<br />
<br />
=Relapsed or refractory=<br />
==Blinatumomab monotherapy {{#subobject:e7b2c6|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:fd494b|Variant=1}}===<br />
{| class="wikitable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://doi.org/10.1200/JCO.2016.67.3301 von Stackelberg et al. 2016 (MT103-205)]<br />
|2012-2014<br />
| style="background-color:#91cf61" |Phase I/II (RT)<br />
|-<br />
|}<br />
''Note: this is the MTD of a phase I/II trial enrolling children under the age of 18.''<br />
====Immunotherapy====<br />
<br />
*[[Blinatumomab (Blincyto)]] as follows:<br />
**Cycle 1: 5 mcg/day IV continuous infusion over 7 days, started on day 1, then 15 mcg/day IV continuous infusion over 21 days, started on day 8 (total dose: 350 mcg)<br />
**Cycles 2 to 5: 28 mcg/day IV continuous infusion over 28 days, started on day 1 (total dose per cycle: 784 mcg)<br />
<br />
'''42-day cycle for up to 5 cycles'''<br />
<br />
===References===<br />
<br />
#'''MT103-205:''' von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, Bader P, O'Brien MM, Brethon B, Bhojwani D, Schlegel PG, Borkhardt A, Rheingold SR, Cooper TM, Zwaan CM, Barnette P, Messina C, Michel G, DuBois SG, Hu K, Zhu M, Whitlock JA, Gore L. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. J Clin Oncol. 2016 Dec 20;34(36):4381-4389. [https://doi.org/10.1200/JCO.2016.67.3301 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/27998223 PubMed] NCT01471782<br />
<br />
==CCE {{#subobject:f74969|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
CCE: '''<u>C</u>'''lofarabine, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide<br />
<br />
===Regimen {{#subobject:24f55b|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2009.07882.x/full Locatelli et al. 2009]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
''Patients in this study were pediatric: ≤ 15 years old at diagnosis and ≤ 21 years old at time of treatment. No patients had CNS disease at time of treatment, and no patients received CNS prophylaxis.''<br />
====Chemotherapy====<br />
<br />
*[[Clofarabine (Clolar)]] 40 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5, given first<br />
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5<br />
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5<br />
<br />
====Supportive medications====<br />
<br />
*Prophylactic [[:Category:Steroids|steroids]] used for patients with greater than 30 x 10<sup>9</sup> blasts/L in the peripheral blood prior to treatment<br />
<br />
'''5-day course'''<br />
<br />
''2 out of 25 patients received a second course of CCE as consolidation therapy. Responding patients were given allogeneic HSCT if a suitable donor was immediately available or were given consolidation courses of chemotherapy including multiple agents active against ALL cells, chosen according to the treating physician's preference."''<br />
<br />
===References===<br />
<br />
#Locatelli F, Testi AM, Bernardo ME, Rizzari C, Bertaina A, Merli P, Pession A, Giraldi E, Parasole R, Barberi W, Zecca M. Clofarabine, cyclophosphamide and etoposide as single-course re-induction therapy for children with refractory/multiple relapsed acute lymphoblastic leukaemia. Br J Haematol. 2009 Nov;147(3):371-8. Epub 2009 Aug 29. [https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2009.07882.x/full link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/19747360 PubMed]<br />
<br />
==Clofarabine monotherapy {{#subobject:6befdc|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:fc17b2|Variant=1}}===<br />
{| class="wikitable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.bloodjournal.org/content/103/3/784.long Jeha et al. 2003]<br />
|2000-2002<br />
| style="background-color:#ffffbe" |Phase 1, <20 pts (RT)<br />
|-<br />
|[https://doi.org/10.1200/JCO.2005.03.8554 Jeha et al. 2006]<br />
|2002-2004<br />
| style="background-color:#91cf61" |Phase II (RT)<br />
|-<br />
|}<br />
''Note: this dose was the MTD in Jeha et al. 2003.''<br />
====Chemotherapy====<br />
<br />
*[[Clofarabine (Clolar)]] 52 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5<br />
<br />
'''2- to 6-week cycles, depending on response count recovery'''<br />
<br />
===References===<br />
<br />
#'''Phase 1:''' Jeha S, Gandhi V, Chan KW, McDonald L, Ramirez I, Madden R, Rytting M, Brandt M, Keating M, Plunkett W, Kantarjian H. Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood. 2004 Feb 1;103(3):784-9. Epub 2003 Oct 9. [http://www.bloodjournal.org/content/103/3/784.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/14551141 PubMed]<br />
#Jeha S, Gaynon PS, Razzouk BI, Franklin J, Kadota R, Shen V, Luchtman-Jones L, Rytting M, Bomgaars LR, Rheingold S, Ritchey K, Albano E, Arceci RJ, Goldman S, Griffin T, Altman A, Gordon B, Steinherz L, Weitman S, Steinherz P. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol. 2006 Apr 20;24(12):1917-23. [https://doi.org/10.1200/JCO.2005.03.8554 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/16622268 PubMed]<br />
<br />
==DOLP {{#subobject:8804f2|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
DOLP: '''<u>D</u>'''aunorubicin, '''<u>O</u>'''ncovin (Vincristine), '''<u>L</u>'''-Asparaginase, '''<u>P</u>'''rednisone<br />
===Regimen {{#subobject:a6fef6|Variant=1}}===<br />
{| class="wikitable" style="width: 40%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.nejm.org/doi/full/10.1056/NEJM198607313150501 Rivera et al. 1986]<br />
| style="background-color:#91cf61" |Non-randomized<br />
|-<br />
|}<br />
====Chemotherapy====<br />
<br />
*[[Daunorubicin (Cerubidine)]]<br />
*[[Vincristine (Oncovin)]]<br />
*[[Asparaginase (Elspar)]]<br />
*[[Prednisone (Sterapred)]]<br />
<br />
'''4-week course'''<br />
====Subsequent treatment====<br />
<br />
*See paper for details of treatment beyond induction<br />
<br />
===References===<br />
<br />
#Rivera GK, Buchanan G, Boyett JM, Camitta B, Ochs J, Kalwinsky D, Amylon M, Vietti TJ, Crist WM; Pediatric Oncology Group. Intensive retreatment of childhood acute lymphoblastic leukemia in first bone marrow relapse: a Pediatric Oncology Group study. N Engl J Med. 1986 Jul 31;315(5):273-8. [https://www.nejm.org/doi/full/10.1056/NEJM198607313150501 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3523250 PubMed]<br />
<br />
==Doxorubicin, Pegaspargase, Vincristine, Prednisone {{#subobject:1265yg|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:3gt03e|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1182/blood.V96.5.1709 Abshire et al. 2000 (POG 9310)]<br />
|NR<br />
| style="background-color:#91cf61" |Non-randomized<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc2654313/ Raetz et al. 2008 (COG AALL01P2)]<br />
|2003-2005<br />
| style="background-color:#91cf61" |Non-randomized portion of RCT<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7776266/ Lew et al. 2021 (COG AALL0433)]<br />
|2007-2013<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Doxorubicin, Pegaspargase, Vincristine, Prednisone; high-dose vincristine<br />
| style="background-color:#d3d3d3" |Not reported<br />
|-<br />
|}<br />
''Note: This is "Block 1" of re-induction. Randomization in COG AALL0433 was discontinued early due to high rates of neuropathy in the experimental arm.''<br />
====Chemotherapy====<br />
<br />
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 1<br />
*[[Pegaspargase (Oncaspar)]] 2500 units/m<sup>2</sup> IM once per day on days 2, 9, 16, 23<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1, 8, 15, 22<br />
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO on days 1 to 29<br />
<br />
====CNS prophylaxis (CNS-)====<br />
<br />
*[[Methotrexate (MTX)]] once per day on days 8 & 29<br />
<br />
====CNS treatment (CNS+)====<br />
<br />
*[[Methotrexate (MTX)]]<br />
*[[Cytarabine (Ara-C)]]<br />
*[[Hydrocortisone (Cortef)]]<br />
<br />
'''5-week course'''<br />
====Subsequent treatment====<br />
<br />
*See papers for details of treatment beyond induction block 1<br />
<br />
===References===<br />
<br />
#'''POG 9310:''' Abshire TC, Pollock BH, Billett AL, Bradley P, Buchanan GR. Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: a Pediatric Oncology Group Study. Blood. 2000 Sep 1;96(5):1709-15. [https://doi.org/10.1182/blood.V96.5.1709 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10961868/ PubMed]<br />
#'''COG AALL01P2:''' Raetz EA, Borowitz MJ, Devidas M, Linda SB, Hunger SP, Winick NJ, Camitta BM, Gaynon PS, Carroll WL. Reinduction platform for children with first marrow relapse of acute lymphoblastic Leukemia: A Children's Oncology Group Study[corrected]. J Clin Oncol. 2008 Aug 20;26(24):3971-8. Erratum in: J Clin Oncol. 2008 Oct 1;26(28): 4697. [https://doi.org/10.1200/jco.2008.16.1414 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc2654313/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/18711187/ PubMed]<br />
#'''COG AALL0433:''' Lew G, Chen Y, Lu X, Rheingold SR, Whitlock JA, Devidas M, Hastings CA, Winick NJ, Carroll WL, Wood BL, Borowitz MJ, Pulsipher MA, Hunger SP. Outcomes after late bone marrow and very early central nervous system relapse of childhood B-acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433. Haematologica. 2021 Jan 1;106(1):46-55. [https://doi.org/10.3324/haematol.2019.237230 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7776266/ link to PMC article] '''does not contain protocol''' [https://pubmed.ncbi.nlm.nih.gov/32001530/ PubMed] NCT00381680<br />
<br />
==Inotuzumab ozogamicin monotherapy {{#subobject:d90806|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:8be9f9|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 60%; text-align:center;" <br />
! style="width: 33%" |Study<br />
! style="width: 33%" |Years of enrollment<br />
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70386-2/fulltext Kantarjian et al. 2012 (MDACC 2009-0872)]<br />
|2010-2011<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Antibody-drug conjugate therapy====<br />
<br />
*[[Inotuzumab ozogamicin (Besponsa)]] 0.8 mg/m<sup>2</sup> IV once on day 1, then 0.5 mg/m<sup>2</sup> IV once per day on days 8 & 15<br />
**For patients achieving CR or CRi, day 1 dose was reduced to 0.5 mg/m<sup>2</sup><br />
<br />
'''21-day cycle for 1 cycle, then 28-day cycle for up to 5 cycles'''<br />
<br />
===References===<br />
<br />
#'''MDACC 2009-0872:''' Kantarjian H, Thomas D, Jorgensen J, Jabbour E, Kebriaei P, Rytting M, York S, Ravandi F, Kwari M, Faderl S, Rios MB, Cortes J, Fayad L, Tarnai R, Wang SA, Champlin R, Advani A, O'Brien S. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol. 2012 Apr;13(4):403-11. Epub 2012 Feb 21. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70386-2/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/22357140 PubMed] NCT01134575<br />
<br />
==Mitoxantrone, Asparaginase Erwinia chrysanthemi, Vincristine, Dexamethasone {{#subobject:910a81|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:ecb2e4|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62002-8/fulltext Parker et al. 2010 (CCLG ALL R3)]<br />
|2003-2007<br />
| style="background-color:#1a9851" |Phase III (E-switch-ic)<br />
|Idarubicin, Asparaginase Erwinia chrysanthemi, Vincristine, Dexamethasone<br />
| style="background-color:#1a9850" |Superior OS<br />
|-<br />
|}<br />
''Note: per the protocol, this regimen is intended only for patients 18 and younger. This regimen is for patients allergic to pegaspargase.''<br />
====Chemotherapy====<br />
<br />
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Asparaginase Erwinia chrysanthemi (Erwinaze)]] 20,000 units IM once per day on days 3, 5, 7, 9, 11, 13, 18, 20, 22, 24, 26, 28<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 3, 10, 17, 24<br />
*[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup> PO once per day on days 1 to 5, 15 to 19<br />
<br />
====CNS prophylaxis====<br />
<br />
*[[Methotrexate (MTX)]] as follows:<br />
**Age less than 2: 8 mg IT once per day on days 1 & 8<br />
**Age 2: 10 mg IT once per day on days 1 & 8<br />
**Age older than 2: 12 mg IT once per day on days 1 & 8<br />
<br />
'''4-week course'''<br />
====Subsequent treatment====<br />
<br />
*See paper for details of treatment beyond induction<br />
<br />
===References===<br />
<br />
#'''CCLG ALL R3:''' Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, Ancliff P, Morgan M, Masurekar A, Goulden N, Green N, Révész T, Darbyshire P, Love S, Saha V. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010 Dec 11;376(9757):2009-17. Epub 2010 Dec 3. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62002-8/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010035/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21131038 PubMed] ISRCTN45724312<br />
<br />
==Mitoxantrone, Pegaspargase, Vincristine, Dexamethasone {{#subobject:910a79|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:e3cbe4|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;"<br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62002-8/fulltext Parker et al. 2010 (CCLG ALL R3)]<br />
|2003-2007<br />
| style="background-color:#1a9851" |Phase III (E-switch-ic)<br />
|Idarubicin, Pegaspargase, Vincristine, Dexamethasone<br />
| style="background-color:#1a9850" |Superior OS<br />
|-<br />
|}<br />
''Note: per the protocol, this regimen is intended only for patients 18 and younger.''<br />
====Chemotherapy====<br />
<br />
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
*[[Pegaspargase (Oncaspar)]] 1000 units/m<sup>2</sup> IM once per day on days 3 & 18<br />
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 3, 10, 17, 24<br />
*[[Dexamethasone (Decadron)]] 20 mg/m<sup>2</sup> PO once per day on days 1 to 5, 15 to 19<br />
<br />
====CNS prophylaxis====<br />
<br />
*[[Methotrexate (MTX)]] as follows:<br />
**Age less than 2: 8 mg IT once per day on days 1 & 8<br />
**Age 2: 10 mg IT once per day on days 1 & 8<br />
**Age older than 2: 12 mg IT once per day on days 1 & 8<br />
<br />
'''4-week course'''<br />
====Subsequent treatment====<br />
<br />
*See paper for details of treatment beyond induction<br />
<br />
===References===<br />
<br />
#'''CCLG ALL R3:''' Parker C, Waters R, Leighton C, Hancock J, Sutton R, Moorman AV, Ancliff P, Morgan M, Masurekar A, Goulden N, Green N, Révész T, Darbyshire P, Love S, Saha V. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010 Dec 11;376(9757):2009-17. Epub 2010 Dec 3. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62002-8/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010035/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21131038 PubMed] ISRCTN45724312<br />
<br />
==Tisagenlecleucel monotherapy {{#subobject:d68f14|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:60fc19|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 25%" |Study<br />
! style="width: 25%" |Years of enrollment<br />
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058440/ Grupp et al. 2013 (Pedi CART19)]<br />
|2011-NR<br />
| style="background-color:#ffffbe" |Pilot<br />
|<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267531/ Maude et al. 2014 (UPCC04409)]<br />
|2012-2014<br />
| style="background-color:#91cf61" |Phase I/IIa<br />
|<br />
|-<br />
|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5996391/ Maude et al. 2018 (ELIANA)]<br />
|2015-2017<br />
| style="background-color:#91cf61" |Phase II (RT)<br />
|ORR: 81%<br />
|-<br />
|}<br />
''Note: dosing instructions are based on ELIANA.''<br />
====Preceding treatment====<br />
<br />
*Lymphodepleting therapy with [[Autologous_HSCT#FC|FC]] or [[Autologous_HSCT#CYVE|CYVE]]<br />
<br />
====Immunotherapy====<br />
<br />
*[[Tisagenlecleucel (Kymriah)]] as follows:<br />
**Up to 50 kg: 2 to 5 x 10<sup>6</sup> CTL019 transduced viable T-cells per kg body weight IV once on day 0<br />
**Greater than 50 kg: 1.0 to 2.5 x 10<sup>8</sup> CTL019 transduced viable T-cells IV once on day 0<br />
<br />
'''One course'''<br />
<br />
===References===<br />
<br />
#'''Pedi CART19:''' Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr 18;368(16):1509-1518. Epub 2013 Mar 25. Erratum in: N Engl J Med. 2016 Mar 10;374(10):998. [https://www.nejm.org/doi/10.1056/NEJMoa1215134 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058440/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23527958 PubMed] NCT01626495<br />
#'''UPCC04409:''' Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct 16;371(16):1507-17. Erratum in: N Engl J Med. 2016 Mar 10;374(10):998. [https://www.nejm.org/doi/10.1056/NEJMoa1407222 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267531/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25317870 PubMed] NCT01029366<br />
#'''ELIANA:''' Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. [https://www.nejm.org/doi/full/10.1056/NEJMoa1709866 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1709866/suppl_file/nejmoa1709866_protocol.pdf link to supplementary protocol] '''contains verified protocol in supplement''' [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5996391/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29385370 PubMed] NCT02435849<br />
<br />
=Consolidation after salvage therapy=<br />
==Blinatumomab monotherapy {{#subobject:e7bh86|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen variant #1, 1 cycle {{#subobject:2db26g|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1001/jama.2021.0987 Locatelli et al. 2021 (Amgen 20120215)]<br />
|2015-2019<br />
| style="background-color:#1a9851" |Phase III (E-switch-ooc)<br />
|Standard salvage consolidation chemotherapy<br />
| style="background-color:#1a9850" |Superior EFS<br />
|-<br />
|}<br />
====Immunotherapy====<br />
<br />
*[[Blinatumomab (Blincyto)]] 15 mcg/m<sup>2</sup>/day IV continuous infusion over 28 days, started on day 1 (total dose: 420 mcg/m<sup>2</sup>)<br />
<br />
'''42-day course'''<br />
====Subsequent treatment====<br />
<br />
*Allogeneic hematopoietic stem cell transplant<br />
<br />
===Regimen variant #2, 2 cycles {{#subobject:2db2g7|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://doi.org/10.1001/jama.2021.0669 Brown et al. 2021 (COG AALL1331)]<br />
|2014-2019<br />
| style="background-color:#1a9851" |Phase III (E-switch-ooc)<br />
|Standard salvage consolidation chemotherapy<br />
| style="background-color:#d9ef8b" |Might have superior DFS<br />
|-<br />
|}<br />
''Note: insufficient dosing information was present in the abstract.''<br />
====Immunotherapy====<br />
<br />
*[[Blinatumomab (Blincyto)]]<br />
<br />
====Subsequent treatment====<br />
<br />
*Allogeneic hematopoietic stem cell transplant<br />
<br />
===References===<br />
<br />
#'''COG AALL1331:''' Brown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowitz MJ, Raetz EA, Zugmaier G, Sharon E, Bernhardt MB, Terezakis SA, Gore L, Whitlock JA, Pulsipher MA, Hunger SP, Loh ML. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):833-842. [https://doi.org/10.1001/jama.2021.0669 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33651090/ PubMed] NCT02101853<br />
#'''Amgen 20120215:''' Locatelli F, Zugmaier G, Rizzari C, Morris JD, Gruhn B, Klingebiel T, Parasole R, Linderkamp C, Flotho C, Petit A, Micalizzi C, Mergen N, Mohammad A, Kormany WN, Eckert C, Möricke A, Sartor M, Hrusak O, Peters C, Saha V, Vinti L, von Stackelberg A. Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):843-854. [https://doi.org/10.1001/jama.2021.0987 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/33651091/ PubMed] NCT02393859<br />
<br />
==Cyclophosphamide & TBI, then allo HSCT {{#subobject:a9e6e8|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation<br />
===Regimen {{#subobject:1ba28d|Variant=1}}===<br />
{| class="wikitable sortable" style="width: 100%; text-align:center;" <br />
! style="width: 20%" |Study<br />
! style="width: 20%" |Years of enrollment<br />
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]<br />
! style="width: 20%" |Comparator<br />
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]<br />
|-<br />
|[https://www.nejm.org/doi/full/10.1056/NEJM198110083051502 Johnson et al. 1981]<br />
|1976-1980<br />
| style="background-color:#91cf61" |Non-randomized<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[https://www.nejm.org/doi/full/10.1056/NEJM198708203170801 Kersey et al. 1987]<br />
|1982-1985<br />
| style="background-color:#1a9851" |Quasi-randomized<br />
|Auto HSCT<br />
| style="background-color:#1a9850" |Superior RFS<br />
|-<br />
|}<br />
{{#lst:Allogeneic HSCT|6ca28d}}<br />
====Immunotherapy====<br />
<br />
*[[Allogeneic stem cells]]<br />
<br />
'''Stem cells transfused on day 0'''<br />
===References===<br />
<br />
#Johnson FL, Thomas ED, Clark BS, Chard RL, Hartmann JR, Storb R. A comparison of marrow transplantation with chemotherapy for children with acute lymphoblastic leukemia in second or subsequent remission. N Engl J Med. 1981 Oct 8;305(15):846-51. [https://www.nejm.org/doi/full/10.1056/NEJM198110083051502 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7024804 PubMed]<br />
#Kersey JH, Weisdorf D, Nesbit ME, LeBien TW, Woods WG, McGlave PB, Kim T, Vallera DA, Goldman AI, Bostrom B, Hurd D, Ramsay NKC. Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphoblastic leukemia. N Engl J Med. 1987 Aug 20;317(8):461-7. [https://www.nejm.org/doi/full/10.1056/NEJM198708203170801 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3302708 PubMed]<br />
<br />
=Further notes=<br />
''Pediatric ALL regimens tend to be very complex. [http://www.ped-onc.org/diseases/ALLtrials/ALLtrials.html This list on ped-onc.org] appears to be fairly comprehensive and includes regimen details for some of the common regimens e.g. COG-AALL0232.'' For now we will try to include a list of references here and potentially build these regimens here, over time.<br />
<br />
[[Category:B-cell acute lymphoblastic leukemia regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Acute lymphoblastic leukemias]]<br />
[[Category:Pediatric hematologic neoplasms]]</div>Waynelianghttps://hemonc.org/w/index.php?title=User:Wayneliang&diff=40654User:Wayneliang2019-10-03T15:23:25Z<p>Wayneliang: Updated broken links</p>
<hr />
<div>[[File:Liang.jpg|thumb|Wayne Liang, MD MS]]<br />
Wayne Liang, MD MS is a pediatric hematology/oncology attending physician at [https://www.childrensal.org/dr-wayne-liang-inf-dis-vir Children's of Alabama] and [https://providerdirectory.uabmedicine.org/provider/Wayne+Liang/573496 University of Alabama at Birmingham Medical Center], with a clinical focus in pediatric leukemias, lymphomas, and histiocytosis. Dr. Liang is an [https://www.uab.edu/medicine/peds/faculty/liang Assistant Professor of Pediatrics (Division of Hematology/Oncology)] and [https://www.uab.edu/medicine/informatics/faculty Informatics Institute] at [http://www.uab.edu/medicine/ University of Alabama at Birmingham School of Medicine]. Dr. Liang's research focuses on the integration and use of genomic information into electronic health records and clinical care workflows to support precision medicine care delivery. He participates as a clinical investigator for childhood cancer clinical trials through the [https://www.childrensoncologygroup.org/ Children's Oncology Group] and other cooperative groups. Dr. Liang is board-certified in Pediatrics, Pediatric Hematology/Oncology, and Clinical Informatics. <br />
<br />
Wayne Liang, MD is the HemOnc.org Section Editor of [[:Category:Pediatric cancers|Pediatric Oncology]].<br />
<br />
==External Links==<br />
<br />
*[https://twitter.com/WayneLiangMD Twitter.com/WayneLiangMD]<br />
*[http://linkedin.com/in/wayneliang LinkedIn]<br />
*[http://www.wayneliangmd.com/ Doximity]</div>Waynelianghttps://hemonc.org/w/index.php?title=User:Wayneliang&diff=40653User:Wayneliang2019-10-03T15:10:58Z<p>Wayneliang: Updated expertise and board certification</p>
<hr />
<div>[[File:Liang.jpg|thumb|Wayne Liang, MD MS]]<br />
Wayne Liang, MD MS is a pediatric hematology/oncology attending physician at [https://www.childrensal.org/dr-wayne-liang-inf-dis-vir Children's of Alabama] and [https://providerdirectory.uabmedicine.org/provider/Wayne+Liang/573496 University of Alabama at Birmingham Medical Center], with a clinical focus in pediatric leukemias, lymphomas, and histiocytosis. Dr. Liang is an [https://www.uab.edu/medicine/peds/hemonc-faculty/1673-wayne-h-liang-md-ms Assistant Professor of Pediatrics (Division of Hematology/Oncology)] and [https://www.uab.edu/medicine/informatics/faculty/faculty Informatics Institute] at [http://www.uab.edu/medicine/ University of Alabama at Birmingham School of Medicine]. Dr. Liang's research focuses on the integration and use of genomic information into electronic health records and clinical care workflows to support precision medicine care delivery. He participates as a clinical investigator for childhood cancer clinical trials through the [https://www.childrensoncologygroup.org/ Children's Oncology Group] and other cooperative groups. Dr. Liang is board-certified in Pediatrics, Pediatric Hematology/Oncology, and Clinical Informatics. <br />
<br />
Wayne Liang, MD is the HemOnc.org Section Editor of [[:Category:Pediatric cancers|Pediatric Oncology]].<br />
<br />
==External Links==<br />
<br />
*[https://twitter.com/WayneLiangMD Twitter.com/WayneLiangMD]<br />
*[http://linkedin.com/in/wayneliang LinkedIn]<br />
*[http://www.wayneliangmd.com/ Doximity]</div>Waynelianghttps://hemonc.org/w/index.php?title=Soft_tissue_sarcoma&diff=26013Soft tissue sarcoma2018-04-05T19:17:04Z<p>Wayneliang: /* Doxorubicin & Ifosfamide (AIM) {{#subobject:e28770|Regimen=1}} */ Add variant 3 regimen source (COG ARST0332 protocol)</p>
<hr />
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<br />
<!--Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]].-->{| class="wikitable" style="text-align:center; width:50%;"<br />
! colspan="2" align="center" style="color:white; font-size:125%; background-color:#08519c" |'''Section editor'''<br />
|-<br />
| style="background-color:#F0F0F0" |[[File:jim_chen.jpeg|frameless|upright=0.3|center]]<br />
|<big>[[User:Jimchen|James L. Chen, MD, MS]]<br>Columbus, OH</big><br>[https://www.linkedin.com/in/jameschen777/ LinkedIn]<br />
|-<br />
|}<br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
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{{TOC limit|limit=3}}<br />
<big>Note: this page is for subtype-nonspecific soft tissue sarcoma regimens, as well as for sarcomas that are not readily categorized, e.g., alveolar soft part sarcoma. Please see the [[:Category:Soft tissue sarcomas|category page]] for links to other sarcoma types.</big><br />
=Guidelines=<br />
==[http://www.esmo.org/ ESMO]==<br />
*'''2014:''' [http://annonc.oxfordjournals.org/content/25/suppl_3/iii102.full.pdf+html Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/25210080 PubMed]<br />
<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf NCCN Guidelines - Soft Tissue Sarcoma]<br />
<br />
=Neoadjuvant therapy=<br />
==Epirubicin & Ifosfamide {{#subobject:eeb76b|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:aea2c8|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30334-0/fulltext Gronchi et al. 2017 (ISG-STS 1001)]<br />
| style="background-color:#1a9851" |Phase III<br />
|Histotype-tailored therapy<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2<br />
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 to 3<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] with [[Ifosfamide (Ifex)]]; abstract does not list dosage/schedule<br />
<br />
'''21-day cycle for 3 cycles, followed by surgery'''<br />
<br />
===References===<br />
# Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, Basso U, Blay JY, Tendero O, Beveridge RD, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Donati DM, Palassini E, Palmerini E, De Sanctis R, Morosi C, Stacchiotti S, Bagué S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017 Jun;18(6):812-822. Epub 2017 May 9. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30334-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28499583 PubMed]<br />
<br />
=Locally advanced or metastatic disease, single-agent regimens=<br />
<br />
==Cisplatin monotherapy {{#subobject:6e93fa|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:2ff0fe|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70102-6/fulltext Blay et al. 2015]<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Cisplatin & Ombrabulin<br />
| style="background-color:#fc8d59" |Seems to have inferior PFS<br />
|-<br />
|}<br />
''Note: PFS was very poor in both groups (less than 2 months); the difference was not considered clinically meaningful.''<br />
====Chemotherapy====<br />
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1<br />
<br />
'''21-day cycles'''<br />
===References===<br />
# Blay JY, Pápai Z, Tolcher AW, Italiano A, Cupissol D, López-Pousa A, Chawla SP, Bompas E, Babovic N, Penel N, Isambert N, Staddon AP, Saâda-Bouzid E, Santoro A, Franke FA, Cohen P, Le-Guennec S, Demetri GD. Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015 May;16(5):531-40. Epub 2015 Apr 8. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70102-6/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25864104 PubMed]<br />
<br />
==Dacarbazine monotherapy {{#subobject:62426f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Variant #1, 850 mg/m<sup>2</sup> {{#subobject:f09c3f|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Eribulin_monotherapy|Eribulin]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Dacarbazine (DTIC)]] 850 mg/m<sup>2</sup> IV over 20 to 120 minutes once on day 1<br />
<br />
'''21-day cycles'''<br />
<br />
===Variant #2, 1000 mg/m<sup>2</sup> {{#subobject:4b5552|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ Demetri et al. 2015]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Trabectedin_monotherapy|Trabectedin]]<br />
| style="background-color:#d73027" |Inferior PFS<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Eribulin_monotherapy|Eribulin]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|}<br />
''Note: this is listed as a "starting dose" in '''Demetri et al. 2015''', but no adjustment instructions were provided in the manuscript.''<br />
====Chemotherapy====<br />
*[[Dacarbazine (DTIC)]] 1000 mg/m<sup>2</sup> IV over 20 to 120 minutes once on day 1<br />
<br />
'''21-day cycles'''<br />
<br />
===Variant #3, 1200 mg/m<sup>2</sup> {{#subobject:2c183b|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://annonc.oxfordjournals.org/content/2/4/307.long Buesa et al. 1991]<br />
| style="background-color:#91cf61" |Phase II<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[http://ascopubs.org/doi/full/10.1200/JCO.2010.33.6107 García-Del-Muro et al. 2011]<br />
| style="background-color:#1a9851" |Randomized phase II<br />
|[[#Dacarbazine_.26_Gemcitabine|Dacarbazine & Gemcitabine]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Eribulin_monotherapy|Eribulin]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Dacarbazine (DTIC)]] 1200 mg/m<sup>2</sup> IV over 20 minutes once on day 1<br />
<br />
====Supportive medications====<br />
*'''Buesa et al. 1991:''' Calcium gluconate (10% solution) 5 mL IV every 10 minutes x 3 doses (total of 15 mL) after the start of dacarbazine; 2 additional doses of calcium gluconate (10% solution) 5 mL IV every 10 minutes were given to patients whose systolic blood pressure decreased below 80 mmHg or heart rate more than 160 bpm.<br />
<br />
'''21-day cycles'''<br />
<br />
===References===<br />
# Buesa JM, Mouridsen HT, van Oosterom AT, Verweij J, Wagener T, Steward W, Poveda A, Vestlev PM, Thomas D, Sylvester R. High-dose DTIC in advanced soft-tissue sarcomas in the adult. A phase II study of the E.O.R.T.C. Soft Tissue and Bone Sarcoma Group. Ann Oncol. 1991 Apr;2(4):307-9. [http://annonc.oxfordjournals.org/content/2/4/307.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1868027 PubMed]<br />
# García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. [http://ascopubs.org/doi/full/10.1200/JCO.2010.33.6107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21606430 PubMed]<br />
# Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. [http://jco.ascopubs.org/content/34/8/786.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26371143 PubMed]<br />
## '''Subgroup analysis:''' Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. [https://www.ncbi.nlm.nih.gov/pubmed/28651804 PubMed]<br />
# Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26874885 PubMed]<br />
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [http://ascopubs.org/doi/full/10.1200/JCO.2016.71.6605 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28854066 PubMed]<br />
<br />
==Doxorubicin monotherapy {{#subobject:826f82|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:62faa6|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.ejcancer.com/article/0277-5379(87)90089-7/fulltext Mouridsen et al. 1987]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Epirubicin_monotherapy|Epirubicin]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
| rowspan="2" |[http://jco.ascopubs.org/content/25/21/3144.long Lorigan et al. 2007]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Ifosfamide_monotherapy|Ifos 3]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[[Soft tissue sarcoma#Ifosfamide_monotherapy|Ifos 9]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70063-4/abstract Judson et al. 2014 (EORTC 62012)]<br />
| style="background-color:#1a9851" |Phase III<br />
|Intensified Doxorubicin & Ifosfamide<br />
| style="background-color:#fee08b" |Might have inferior OS<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30587-6/fulltext Tap et al. 2016]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Doxorubicin_.26_Olaratumab|Doxorubicin & Olaratumab]]<br />
| style="background-color:#d73027" |Inferior OS<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30381-9/fulltext Tap et al. 2017 (TH CR-406/SARC021)]<br />
| style="background-color:#1a9851" |Phase III<br />
|Doxorubicin & Evofosfamide<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ Seddon et al. 2017 (GeDDiS)]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Docetaxel_.26_Gemcitabine|Docetaxel & Gemcitabine]]<br />
| style="background-color:#d9ef8b" |Might have superior PFS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV bolus once on day 1<br />
<br />
====Supportive medications====<br />
*In Tap et al. 2016, [[Dexrazoxane (Zinecard)]] (dose not specified) could be used on day 1 of every cycle to reduce the potential for doxorubicin-related cardiotoxicity in cycles 5 to 8<br />
<br />
'''21-day cycle for up to 6 to 8 cycles, until progression of disease, unacceptable toxicity, or patient refusal''' <br />
<br />
''Note: in '''Mouridsen et al. 1987''', treatment was given until progression of disease, unacceptable toxicity, or cumulative doxorubicin dosage of 550 mg/m<sup>2</sup>, though the ultimate decision to stop treatment based on cumulative doxorubicin dosage was at the discretion of the treating physician.''<br />
<br />
===References===<br />
# Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D et al. Adriamycin versus epirubicin in advanced soft tissue sarcomas. A randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. [http://www.ejcancer.com/article/0277-5379(87)90089-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3479329 PubMed]<br />
# '''Meta-analysis''' Bramwell VH, Anderson D, Charette ML. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: a meta-analysis and clinical practice guideline. Sarcoma. 2000;4(3):103-12. [http://www.hindawi.com/journals/srcm/2000/149793/abs/ link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2395439/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18521288 PubMed]<br />
# Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. [http://jco.ascopubs.org/content/25/21/3144.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17634494 PubMed]<br />
# Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay JY, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, Krarup-Hansen A, Alcindor T, Marreaud S, Litière S, Hermans C, Fisher C, Hogendoorn PC, dei Tos AP, van der Graaf WT; European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014 Apr;15(4):415-23. Epub 2014 Mar 5. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70063-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24618336 PubMed]<br />
# Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30587-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27291997 PubMed]<br />
# Tap WD, Papai Z, Van Tine BA, Attia S, Ganjoo KN, Jones RL, Schuetze S, Reed D, Chawla SP, Riedel RF, Krarup-Hansen A, Toulmonde M, Ray-Coquard I, Hohenberger P, Grignani G, Cranmer LD, Okuno S, Agulnik M, Read W, Ryan CW, Alcindor T, Del Muro XFG, Budd GT, Tawbi H, Pearce T, Kroll S, Reinke DK, Schöffski P. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1089-1103. Epub 2017 Jun 23. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30381-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28651927 PubMed]<br />
# Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30622-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28882536 PubMed]<br />
<br />
==Epirubicin monotherapy {{#subobject:d976a5|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
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|}<br />
<br />
===Regimen {{#subobject:a1dd30|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.sciencedirect.com/science/article/pii/0277537987900897 Mouridsen et al. 1987]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Doxorubicin_monotherapy|Doxorubicin]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV bolus once on day 1<br />
<br />
'''21-day cycles, given until progression of disease, unacceptable toxicity, or cumulative epirubicin dosage of 550 mg/m<sup>2</sup>''' (though the ultimate decision to stop treatment based on cumulative epirubicin dosage was at the discretion of the treating physician)<br />
<br />
===References===<br />
# Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D et al. Adriamycin versus epirubicin in advanced soft tissue sarcomas. A randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. [http://www.sciencedirect.com/science/article/pii/0277537987900897 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3479329 PubMed]<br />
<br />
==Eribulin monotherapy {{#subobject:427859|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
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|}<br />
<br />
===Regimen {{#subobject:2bcda0|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Dacarbazine_monotherapy|Dacarbazine]]<br />
| style="background-color:#91cf60" |Seems to have superior OS<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
<br />
'''21-day cycles until progression'''<br />
<br />
===References===<br />
# Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26874885 PubMed]<br />
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [http://ascopubs.org/doi/full/10.1200/JCO.2016.71.6605 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28854066 PubMed]<br />
<br />
==Ifosfamide monotherapy {{#subobject:88d059|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
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|}<br />
<br />
===Variant #1, short infusion (Ifos 3) {{#subobject:89c8f1|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://jco.ascopubs.org/content/25/21/3144.long Lorigan et al. 2007]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Doxorubicin_monotherapy|Doxorubicin]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|Ifos 9<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3<br />
**Each day's dose of ifosfamide is mixed together with [[Mesna (Mesnex)]] in 1 liter of normal saline<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] as follows:<br />
**600 mg/m<sup>2</sup> IV bolus once on day 1, '''given immediately prior to mesna/ifosfamide infusion''', then<br />
**1500 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3, given together with [[Ifosfamide (Ifex)]], then<br />
**1200 mg/m<sup>2</sup> IV two times per day on days 1 to 3, given at 4 and 8 hours after completion of ifosfamide and mesna<br />
***An alternative is to use oral mesna instead of intravenous: [[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup> PO two times per day on days 1 to 3, given at 2 and 6 hours after completion of ifosfamide and mesna<br />
*Sodium bicarbonate 150 mmol IV once per day on days 1 to 3<br />
*Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion<br />
<br />
'''21-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or patient refusal'''<br />
<br />
===Variant #2, continuous infusion (Ifos 9) {{#subobject:ad63a|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://jco.ascopubs.org/content/25/21/3144.long Lorigan et al. 2007]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Doxorubicin_monotherapy|Doxorubicin]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|Ifos 3<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours (total dose per cycle: 9000 mg/m<sup>2</sup>) on days 1 to 3, given together with mesna<br />
**Each day's dose is mixed together with mesna in 3 liters of normal saline<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] as follows:<br />
**600 mg/m<sup>2</sup> IV bolus once on day 1, immediately prior to mesna/ifosfamide infusion, then<br />
**3000 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours (total dose per cycle: 9000 mg/m<sup>2</sup>) on days 1 to 3, given together with [[Ifosfamide (Ifex)]], then<br />
**1800 mg/m<sup>2</sup> IV over 12 hours once on day 4, starting after completion of ifosfamide and mesna<br />
***An alternative is to use oral mesna instead of intravenous: [[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup> PO three times on day 4, given 0, 2, and 6 hours after completion of ifosfamide and mesna<br />
*Sodium bicarbonate 150 mmol IV once per day on days 1 to 3<br />
*Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion<br />
<br />
'''21-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or patient refusal'''<br />
<br />
===Variant #3 {{#subobject:210d2d|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.ejcancer.com/article/S0959-8049(02)00491-4/fulltext van Oosterom et al. 2002]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 3<br />
**Each day's dose is dissolved in 125 mL sterile water per 1000 mg of ifosfamide, mixed together with [[Mesna (Mesnex)]] in an additional 1 liter of dextrose/saline<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] as follows:<br />
**600 mg/m<sup>2</sup> IV bolus once on day 1, immediately prior to mesna/ifosfamide infusion, then<br />
**1500 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3, given together with [[Ifosfamide (Ifex)]], then<br />
**500 mg/m<sup>2</sup> IV two times per day on days 1 to 3, given at 4 and 8 hours after completion of ifosfamide and mesna<br />
*"[[:Category:Emesis_prevention|Antiemetics]] were prescribed according to local conventions"<br />
*1 liter of fluid PO two times per day on days 1 to 3, taken 4 and 8 hours after completion of ifosfamide and mesna<br />
<br />
'''21-day cycle for at least 2 cycles, except in cases of rapid disease progression; continued until disease progression or unacceptable toxicity or patient refusal'''<br />
<br />
===References===<br />
# van Oosterom AT, Mouridsen HT, Nielsen OS, Dombernowsky P, Krzemieniecki K, Judson I, Svancarova L, Spooner D, Hermans C, Van Glabbeke M, Verweij J; EORTC Soft Tissue and Bone Sarcoma Group. Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients. Eur J Cancer. 2002 Dec;38(18):2397-406 [http://www.ejcancer.com/article/S0959-8049(02)00491-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12460784 PubMed] content property of [http://hemonc.org HemOnc.org]<br />
# Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. [http://jco.ascopubs.org/content/25/21/3144.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17634494 PubMed]<br />
<br />
==Pazopanib monotherapy {{#subobject:644c8f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:332a64|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract van der Graaf et al. 2012 (PALETTE)]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Placebo|Placebo]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Pazopanib (Votrient)]] 800 mg PO once per day<br />
<br />
'''Given until progression of disease, unacceptable toxicity, withdrawal of consent, or death'''<br />
<br />
===References===<br />
# van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Sch?ffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. Epub 2012 May 16. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22595799 PubMed]<br />
<br />
==Placebo==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract van der Graaf et al. 2012 (PALETTE)]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Pazopanib_monotherapy|Pazopanib]]<br />
| style="background-color:#d73027" |Inferior PFS<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70098-7/fulltext Kawai et al. 2015]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Trabectedin_monotherapy|Trabectedin]]<br />
| style="background-color:#d73027" |Inferior PFS<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/fulltext Mir et al. 2016 (REGOSARC)]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Regorafenib_monotherapy|Regorafenib]]<br />
| style="background-color:#d73027" |Inferior PFS (*)<br />
|-<br />
|}<br />
<br />
''No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only. Note: reported efficacy in '''REGOSARC''' is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.''<br />
<br />
===References===<br />
# van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Sch?ffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. Epub 2012 May 16. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22595799 PubMed]<br />
# Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015 Apr;16(4):406-16. Epub 2015 Mar 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70098-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25795406 PubMed]<br />
# Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27751846 PubMed]<br />
<br />
==Regorafenib monotherapy {{#subobject:c9fc2c|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:b5ff4e|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/fulltext Mir et al. 2016 (REGOSARC)]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Placebo|Placebo]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
''Note: reported efficacy is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.''<br />
====Chemotherapy====<br />
*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21<br />
<br />
'''28-day cycles'''<br />
<br />
===References===<br />
# Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27751846 PubMed]<br />
<br />
==Temozolomide monotherapy {{#subobject:5929ed|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Variant #1 {{#subobject:63d3d8|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.11730/full Talbot et al. 2003]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> (doses rounded up if needed to next available dosage based on capsule doses) PO once on day 1, on an empty stomach; then 12 hours later, 90 mg/m<sup>2</sup> PO once every 12 hours x 9 doses (total of 10 doses per cycle) on days 1 to 5, on an empty stomach<br />
<br />
====Supportive medications====<br />
*[[:Category:Emesis_prevention|Antiemetics]] "prescribed as clinically indicated by the treating physician"<br />
<br />
'''28-day cycles, given until progression of disease or 1 year; patients on study could be reconsented to receive therapy beyond 1 year'''<br />
<br />
===Variant #2 {{#subobject:892d65|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.21384/full Garcia del Muro et al. 2005]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Temozolomide (Temodar)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 42 (6 weeks), with no food 1 hour before and after temozolomide doses<br />
**Initial dose used in the study was 75 mg/m<sup>2</sup>, but due to lack of toxicity, protocol was amended to use 100 mg/m<sup>2</sup> doses<br />
<br />
====Supportive medications====<br />
*"[[:Category:Emesis_prevention|Antiemetics]], mainly oral [[Metoclopramide (Reglan)]] and [[Ondansetron (Zofran)]], were prescribed as clinically indicated by the treating physician"<br />
<br />
'''9-week cycle for up to 3 cycles, progression of disease, or unacceptable toxicity'''<br />
<br />
===References===<br />
# Talbot SM, Keohan ML, Hesdorffer M, Orrico R, Bagiella E, Troxel AB, Taub RN. A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer. 2003 Nov 1;98(9):1942-6. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.11730/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14584078 PubMed]<br />
# Garcia del Muro X, Lopez-Pousa A, Martin J, Buesa JM, Martinez-Trufero J, Casado A, Poveda A, Cruz J, Bover I, Maurel J; Spanish Group for Research on Sarcomas. A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma: a study by the Spanish Group for Research on Sarcomas. Cancer. 2005 Oct 15;104(8):1706-12. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.21384/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16134177 PubMed]<br />
<br />
==Trabectedin monotherapy {{#subobject:cfc3ed|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Variant #1 {{#subobject:05c55d|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ Demetri et al. 2015]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Dacarbazine_monotherapy|Dacarbazine]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
''Note: this is listed as a "starting dose," but no adjustment instructions were provided in the manuscript.''<br />
====Chemotherapy====<br />
*[[Trabectedin (Yondelis)]] 1.5 mg/m<sup>2</sup> IV continuous infusion over 24 hours, starting on day 1<br />
<br />
====Supportive medications====<br />
*[[Dexamethasone (Decadron)]] 20 mg IV once prior to trabectedin<br />
<br />
'''21-day cycles'''<br />
<br />
===Variant #2 {{#subobject:33de2b|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70098-7/fulltext Kawai et al. 2015]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Placebo|Placebo]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Trabectedin (Yondelis)]] 1.2 mg/m<sup>2</sup> IV continuous infusion over 24 hours, starting on day 1<br />
<br />
'''21-day cycles'''<br />
<br />
===References===<br />
# Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gómez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. Epub 2009 Aug 3. [http://ascopubs.org/doi/full/10.1200/JCO.2008.21.0088 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19652065 PubMed]<br />
# Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015 Apr;16(4):406-16. Epub 2015 Mar 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70098-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25795406 PubMed]<br />
# Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. [http://jco.ascopubs.org/content/34/8/786.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26371143 PubMed]<br />
## '''Subgroup analysis:''' Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. [https://www.ncbi.nlm.nih.gov/pubmed/28651804 PubMed]<br />
<br />
=Locally advanced or metastatic disease, combination regimens=<br />
<br />
==Doxorubicin & Ifosfamide (AIM) {{#subobject:e28770|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
AIM: '''<u>A</u>'''driamycin (doxorubicin), '''<u>I</u>'''fosfamide, '''<u>M</u>'''esna<br />
<br />
===Variant #1, 5-day course, lower dose doxorubicin - AI 75/10 {{#subobject:9c1374|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=1998&issue=06000&article=00025&type=abstract Patel et al. 1998]<br />
| style="background-color:#ffffbe" |Pilot, <20 patients reported<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours on days 1 to 3 (total dose per cycle: 75 mg/m<sup>2</sup>) <br />
*[[Ifosfamide (Ifex)]] 2000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5 (total dose per cycle: 10,000 mg/m<sup>2</sup>)<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] 400 mg/m<sup>2</sup> IV once on day 1, given simultaneously with the first dose of [[Ifosfamide (Ifex)]]<br />
*[[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 6000 mg/m<sup>2</sup>)<br />
**Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate<br />
*If febrile neutropenia occurs, [[:Category:Granulocyte colony-stimulating factors|G-CSF]] is used in subsequent cycles <br />
<br />
'''21-day cycles, given until maximum response, 6 cycles of therapy, progression of disease, or unacceptable toxicity'''<br />
<br />
===Variant #2, 4-day course, higher dose doxorubicin - AI 90/10 {{#subobject:2fd91c|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=1998&issue=06000&article=00025&type=abstract Patel et al. 1998]<br />
| style="background-color:#ffffbe" |Pilot, <20 patients reported<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours on days 1 to 3 (total dose per cycle: 90 mg/m<sup>2</sup>) <br />
*[[Ifosfamide (Ifex)]] 2500 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 4 (total dose per cycle: 10,000 mg/m<sup>2</sup>)<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] 500 mg/m<sup>2</sup> IV once on day 1, given simultaneously with the first dose of [[Ifosfamide (Ifex)]]<br />
*[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion over 4 days on days 1 to 4 (total dose per cycle: 6000 mg/m<sup>2</sup>)<br />
**Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate<br />
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 5 mcg/kg (dose rounded to 300 or 480 mcg) SC once per day, starting on day 5, given until ANC is at least 10,000/uL<br />
<br />
'''21-day cycles, given until maximum response, 6 cycles of therapy, progression of disease, or unacceptable toxicity'''<br />
<br />
=== Variant #3, 3-day course, lower dose doxorubicin and ifosfamide {{#subobject:0acb5d|Variant=1}} ===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://ascopubs.org/doi/abs/10.1200/jco.2015.33.15_suppl.10012 Venkatramani et al. 2015 (COG ARST0332 Arm D)]<br />
| style="background-color:#91cf61" |Phase III Non-randomized prospective trial<br />
|-<br />
|}<br />
<br />
''Note: Regimen details are derived from the COG ARST0332 ([https://clinicaltrials.gov/ct2/show/NCT00346164 NCT00346164]) protocol.''<br />
<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 37.5 mg/m<sup>2</sup>/day (maximum 75 mg/dose) IV continuous infusion over 24 hours on days 1 and 2 (total dose per cycle: 75 mg/m<sup>2</sup>)<br />
**Given only 5 out of 6 cycles, for a total regimen dose of 375 mg/m<sup>2</sup>. <br />
**Doses are held when patients are receiving concurrent radiation therapy (for example, held during cycles 2 and 3, if radiation therapy is initiated with cycle 2). The missed doses are then administered in a different cycle, to maintain a total regimen dose of 375 mg/m<sup>2</sup>. If doses are held in 2 of 6 cycles, a doxorubicin-only "Cycle 7" may be given 21 days following cycle 6. <br />
*[[Ifosfamide (Ifex)]] 3 g/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3 (total dose per cycle: 9 g/m<sup>2</sup>)<br />
**Given all 6 cycles, for a total regimen dose of 54 g/m<sup>2</sup>.<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup> IV over 15 minutes given at 15 minutes before each dose of [[Ifosfamide (Ifex)]], then at 3 hours, 6 hours, and 9 hours after start of [[Ifosfamide (Ifex)]]<br />
*Hydration:<br />
**Before first [[Ifosfamide (Ifex)]] infusion: D5 1/2 NS IV at rate of 200 mL/m<sup>2</sup>/hr IV until urine output > 2 cc/kg/hr<br />
**With [[Ifosfamide (Ifex)]] infusion: D5 1/2 NS with 10 mEq KCL/L IV at rate of 125 mL/m<sup>2</sup>/hr IV beginning immediately after ifosfamide infusion and continuing until next ifosfamide dose, or until 24 hours after last dose.<br />
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 5 mcg/kg (max 480 mcg) SC once per day, starting on day 4, given until ANC is at least 2,000/uL after nadir. Filgrastim should not be administered within 24 hours of chemotherapy.<br />
<br />
'''21-day cycles, given until 6 cycles of therapy, progression of disease, or unacceptable toxicity'''<br />
<br />
==== Radiotherapy ====<br />
* Beginning with cycle 2 (week 4)<br />
* Doxorubicin is held for cycles which occur while receiving radiation therapy. <br />
<br />
==== Surgery ====<br />
* Definitive resection of primary tumor after recovery from cycle 3 (week 13)<br />
* Definitive resection of residual metastasis after completion of chemotherapy<br />
<br />
===References===<br />
# Patel SR, Vadhan-Raj S, Burgess MA, Plager C, Papadopolous N, Jenkins J, Benjamin RS. Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Am J Clin Oncol. 1998 Jun;21(3):317-21. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=1998&issue=06000&article=00025&type=abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9626808 PubMed]<br />
# '''Abstract:''' Venkatramani R, Anderson JR, Million L, Coffin CM, McCarville B, Randall RL, et al. Risk-based treatment for synovial sarcoma in patients under 30 years of age: Children’s Oncology Group study ARST0332. J Clin Oncol [Internet]. 2015;33(15). [http://ascopubs.org/doi/abs/10.1200/jco.2015.33.15_suppl.10012 link to original abstract] '''contains protocol'''<br />
<br />
==Dacarbazine & Gemcitabine {{#subobject:cd9068|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:9aaddf|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://ascopubs.org/doi/full/10.1200/JCO.2010.33.6107 García-Del-Muro et al. 2011]<br />
| style="background-color:#1a9851" |Randomized phase II<br />
|[[#Dacarbazine_monotherapy|Dacarbazine]]<br />
| style="background-color:#91cf60" |Seems to have superior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Dacarbazine (DTIC)]] 500 mg/m<sup>2</sup> IV over 20 minutes once on day 1, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 1800 mg/m<sup>2</sup> IV over 3 hours (fixed-dose rate) once on day 1, '''given first'''<br />
<br />
'''14-day cycle for 12 cycles, or longer per clinician discretion'''<br />
<br />
===References===<br />
# García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. [http://ascopubs.org/doi/full/10.1200/JCO.2010.33.6107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21606430 PubMed]<br />
<br />
==Docetaxel & Gemcitabine {{#subobject:1e718f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Variant #1, 60/675 {{#subobject:270ac9|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;"<br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372854/ Hensley et al. 2015 (GOG-250)]<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Docetaxel, Gemcitabine, Bevacizumab<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
''This regimen was intended for patients who received prior radiation.''<br />
====Chemotherapy====<br />
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 675 mg/m<sup>2</sup> IV over 70 to 90 minutes once per day on days 1 & 8, '''given first'''<br />
<br />
'''21-day cycles''' <br />
<br />
===Variant #2, 75/675 {{#subobject:2898f9|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://jco.ascopubs.org/content/20/12/2824.long Hensley et al. 2002]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen was intended for patients who received prior radiation.''<br />
====Chemotherapy====<br />
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 675 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8, '''given first'''<br />
<br />
====Supportive medications====<br />
*[[Dexamethasone (Decadron)]] 8 mg PO BID on days 7-9 (the day before, the day of, and day after [[Docetaxel (Taxotere)]])<br />
*Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel<br />
*One of the following growth factors (varies depending on reference):<br />
**[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 150 mcg/m<sup>2</sup> (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements<br />
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on either day 9 or 10 (only one dose given)<br />
<br />
'''21-day cycle for 6 to 8 cycles'''; Hensley et al. 2008 did not specify a maximum number of cycles<br />
<br />
===Variant #3, 75/900 {{#subobject:2a13c9|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;"<br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372854/ Hensley et al. 2015 (GOG-250)]<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Docetaxel, Gemcitabine, Bevacizumab<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
''This regimen was intended for patients with no prior radiation.''<br />
====Chemotherapy====<br />
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 900 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8, '''given first'''<br />
<br />
'''21-day cycles''' <br />
<br />
===Variant #3, 100/900 {{#subobject:d89e30|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://jco.ascopubs.org/content/20/12/2824.long Hensley et al. 2002]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen was intended for patients with no prior radiation.''<br />
====Chemotherapy====<br />
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 900 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8, '''given first'''<br />
<br />
====Supportive medications====<br />
*[[Dexamethasone (Decadron)]] 8 mg PO BID on days 7 to 9 (the day before, the day of, and day after [[Docetaxel (Taxotere)]])<br />
*Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel<br />
*One of the following growth factors (varies depending on reference):<br />
**[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 150 mcg/m<sup>2</sup> (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements<br />
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on either day 9 or 10 (only one dose given)<br />
<br />
'''21-day cycle for 6 to 8 cycles'''; Hensley et al. 2008 did not specify a maximum number of cycles<br />
<br />
===References===<br />
# Hensley ML, Maki R, Venkatraman E, Geller G, Lovegren M, Aghajanian C, Sabbatini P, Tong W, Barakat R, Spriggs DR. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. 2002 Jun 15;20(12):2824-31. [http://jco.ascopubs.org/content/20/12/2824.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12065559 PubMed]<br />
# Hensley ML, Blessing JA, Mannel R, Rose PG. Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 2008 Jun;109(3):329-34. [http://www.gynecologiconcology-online.net/article/S0090-8258(08)00204-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504727/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18534250 PubMed]<br />
# '''GOG-250:''' Hensley ML, Miller A, O'Malley DM, Mannel RS, Behbakht K, Bakkum-Gamez JN, Michael H. Randomized phase III trial of gemcitabine plus docetaxel plus bevacizumab or placebo as first-line treatment for metastatic uterine leiomyosarcoma: an NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol. 2015 Apr 1;33(10):1180-5. Epub 2015 Feb 23. [http://ascopubs.org/doi/full/10.1200/JCO.2014.58.3781 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372854/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25713428 PubMed]<br />
# '''GeDDiS:''' Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30622-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28882536 PubMed]<br />
<br />
==Doxorubicin & Olaratumab {{#subobject:31132d|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:24a882|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30587-6/fulltext Tap et al. 2016]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Doxorubicin_monotherapy|Doxorubicin]]<br />
| style="background-color:#1a9850" |Superior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] as follows:<br />
**Cycles 1 to 8: 75 mg/m<sup>2</sup> IV once on day 1<br />
*[[Olaratumab (Lartruvo)]] 15 mg/kg IV once per day on days 1 & 8<br />
<br />
'''21-day cycles''' <br />
<br />
====Supportive medications====<br />
*In Tap et al. 2016, [[Dexrazoxane (Zinecard)]] (dose not specified) could be used on day 1 of every cycle to reduce the potential for doxorubicin-related cardiotoxicity in cycles 5 to 8<br />
<br />
===References===<br />
# Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. Epub 2016 Jun 9. Erratum in: Lancet. 2016 Jul 30;388(10043):464. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30587-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27291997 PubMed]<br />
<br />
==Epirubicin & Ifosfamide {{#subobject:820f20|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:55e5db|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://jco.ascopubs.org/content/16/4/1438.long Reichardt et al. 1998]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Epirubicin (Ellence)]] 45 mg/m<sup>2</sup>/day IV continuous infusion over 2 days on days 2 & 3 (total dose per cycle: 90 mg/m<sup>2</sup>)<br />
*[[Ifosfamide (Ifex)]] 2500 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 12,500 mg/m<sup>2</sup>)<br />
**Each day's dose is mixed together with [[Mesna (Mesnex)]] in 3 liters of "fluids with electrolytes"<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup> IV continuous infusion over 5 days on days 1 to 5, given together with [[Ifosfamide (Ifex)]] (total dose per cycle: 7500 mg/m<sup>2</sup>) <br />
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 5 mcg/kg SC once per day on days 6 to 15 or "until recovery of leukocytes"<br />
*[[Ondansetron (Zofran)]] 8-24 mg per day prn nausea<br />
*[[Dexamethasone (Decadron)]] (dose/schedule not specified) for antiemesis if necessary<br />
<br />
'''21-day cycles'''<br />
<br />
===References===<br />
# Reichardt P, Tilgner J, Hohenberger P, D?rken B. Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study. J Clin Oncol. 1998 Apr;16(4):1438-43. [http://jco.ascopubs.org/content/16/4/1438.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9552049 PubMed]<br />
<br />
==Gemcitabine & Vinorelbine {{#subobject:4dd538|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:b605f7|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.22609/full Dileo et al. 2007]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8<br />
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1 & 8<br />
<br />
'''21-day cycles'''<br />
<br />
===Reference===<br />
# Dileo P, Morgan JA, Zahrieh D, Desai J, Salesi JM, Harmon DC, Quigley MT, Polson K, Demetri GD, George S. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer. 2007 May 1;109(9):1863-9. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.22609/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17385194 PubMed]<br />
<br />
=Liposarcoma, all lines of therapy=<br />
''Note: this will be moved to a histology-specific page, shortly.''<br />
==Eribulin monotherapy {{#subobject:427859|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:2bcda0|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Dacarbazine_monotherapy|Dacarbazine]]<br />
| style="background-color:#1a9850" |Superior OS (*)<br />
|-<br />
|}<br />
''Efficacy is based on the 2017 subgroup analysis.''<br />
====Chemotherapy====<br />
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
<br />
'''21-day cycles until progression'''<br />
<br />
===References===<br />
# Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26874885 PubMed]<br />
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [http://ascopubs.org/doi/full/10.1200/JCO.2016.71.6605 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28854066 PubMed]<br />
<br />
=Rhabdomyosarcoma, all lines of therapy=<br />
''Note: this will be moved to a histology-specific page, shortly.''<br />
==VAC {{#subobject:4f2267|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VAC: '''<u>V</u>'''incristine, '''<u>A</u>'''ctinomycin D, '''<u>C</u>'''yclophosphamide<br />
===Regimen {{#subobject:060d90|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 Crist et al. 2001 (IRS-IV)]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[#VAI|VAI]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[[#VIE|VIE]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
To be completed<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]]<br />
*[[Dactinomycin (Cosmegen)]]<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
<br />
===References===<br />
# Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091-102. [http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11408506 PubMed]<br />
<br />
==VAI {{#subobject:9ab538|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VAI: '''<u>V</u>'''incristine, '''<u>A</u>'''ctinomycin D, '''<u>I</u>'''fosfamide<br />
<br>IVA: '''<u>I</u>'''fosfamide, '''<u>V</u>'''incristine, '''<u>A</u>'''ctinomycin D<br />
===Regimen {{#subobject:49f6c6|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 Crist et al. 2001 (IRS-IV)]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[#VAC|VAC]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[[#VIE|VIE]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[http://ascopubs.org/doi/full/10.1200/JCO.2011.40.3287 Oberlin et al. 2012 (SIOP MMT95)]<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|IVA/CEV/IVE<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
To be completed<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]]<br />
*[[Dactinomycin (Cosmegen)]]<br />
*[[Ifosfamide (Ifex)]]<br />
<br />
===References===<br />
# Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091-102. [http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11408506 PubMed]<br />
# Oberlin O, Rey A, Sanchez de Toledo J, Martelli H, Jenney ME, Scopinaro M, Bergeron C, Merks JH, Bouvet N, Ellershaw C, Kelsey A, Spooner D, Stevens MC. Randomized comparison of intensified six-drug versus standard three-drug chemotherapy for high-risk nonmetastatic rhabdomyosarcoma and other chemotherapy-sensitive childhood soft tissue sarcomas: long-term results from the International Society of Pediatric Oncology MMT95 study. J Clin Oncol. 2012 Jul 10;30(20):2457-65. Epub 2012 Jun 4. [http://ascopubs.org/doi/full/10.1200/JCO.2011.40.3287 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22665534 PubMed]<br />
<br />
==VI, then VDC/IE, then VAC, then VI {{#subobject:e080ff|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VI, then VDC/IE, then VAC, then VI: '''<u>V</u>'''incristine & '''<u>I</u>'''rinotecan, followed by '''<u>V</u>'''incristine, '''<u>D</u>'''oxorubicin, '''<u>C</u>'''yclophosphamide alternating with '''<u>I</u>'''fosfamide & '''<u>E</u>'''toposide, followed by '''<u>V</u>'''incristine, '''<u>A</u>'''ctinomycin D, '''<u>C</u>'''yclophosphamide, followed by '''<u>V</u>'''incristine & '''<u>I</u>'''rinotecan<br />
===Regimen {{#subobject:9a3f8d|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070550/ Weigel et al. 2015 (COG ARST0431)]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''Note: this is a complicated 54-week regimen with no immediate plans to add it to HemOnc.org. Please refer to the original article.''<br />
===References===<br />
# Weigel BJ, Lyden E, Anderson JR, Meyer WH, Parham DM, Rodeberg DA, Michalski JM, Hawkins DS, Arndt CA. Intensive multiagent therapy, including dose-compressed cycles of ifosfamide/etoposide and vincristine/doxorubicin/cyclophosphamide, irinotecan, and radiation, in patients with high-risk rhabdomyosarcoma: A report from the Children's Oncology Group. J Clin Oncol. 2016 Jan 10;34(2):117-22. Epub 2015 Oct 26. [http://ascopubs.org/doi/full/10.1200/JCO.2015.63.4048 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070550/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26503200 PubMed]<br />
<br />
==VIE {{#subobject:1b4037|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VIE: '''<u>V</u>'''incristine, '''<u>I</u>'''fosfamide, '''<u>E</u>'''toposide<br />
===Regimen {{#subobject:f0d233|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 Crist et al. 2001 (IRS-IV)]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[#VAC|VAC]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[[#VAI|VAI]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
To be completed<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]]<br />
*[[Ifosfamide (Ifex)]]<br />
*[[Etoposide (Vepesid)]]<br />
<br />
===References===<br />
# Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091-102. [http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11408506 PubMed]<br />
<br />
=Gastrointestinal stromal tumor (GIST), all lines of therapy=<br />
''Please see the [[Gastrointestinal stromal tumor|dedicated GIST page]].''<br />
<br />
[[Category:Soft tissue sarcoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Soft tissue sarcomas]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Soft_tissue_sarcoma&diff=26006Soft tissue sarcoma2018-04-05T15:11:57Z<p>Wayneliang: /* Doxorubicin & Ifosfamide (AIM) {{#subobject:e28770|Regimen=1}} */ color change for evidence to light green</p>
<hr />
<div><!--'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]]. If this is your first time visiting, we suggest you read the [[tutorial]].'''--><br />
<br />
<!--Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]].-->{| class="wikitable" style="text-align:center; width:50%;"<br />
! colspan="2" align="center" style="color:white; font-size:125%; background-color:#08519c" |'''Section editor'''<br />
|-<br />
| style="background-color:#F0F0F0" |[[File:jim_chen.jpeg|frameless|upright=0.3|center]]<br />
|<big>[[User:Jimchen|James L. Chen, MD, MS]]<br>Columbus, OH</big><br>[https://www.linkedin.com/in/jameschen777/ LinkedIn]<br />
|-<br />
|}<br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=3}}<br />
<big>Note: this page is for subtype-nonspecific soft tissue sarcoma regimens, as well as for sarcomas that are not readily categorized, e.g., alveolar soft part sarcoma. Please see the [[:Category:Soft tissue sarcomas|category page]] for links to other sarcoma types.</big><br />
=Guidelines=<br />
==[http://www.esmo.org/ ESMO]==<br />
*'''2014:''' [http://annonc.oxfordjournals.org/content/25/suppl_3/iii102.full.pdf+html Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/25210080 PubMed]<br />
<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf NCCN Guidelines - Soft Tissue Sarcoma]<br />
<br />
=Neoadjuvant therapy=<br />
==Epirubicin & Ifosfamide {{#subobject:eeb76b|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:aea2c8|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30334-0/fulltext Gronchi et al. 2017 (ISG-STS 1001)]<br />
| style="background-color:#1a9851" |Phase III<br />
|Histotype-tailored therapy<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2<br />
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 to 3<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] with [[Ifosfamide (Ifex)]]; abstract does not list dosage/schedule<br />
<br />
'''21-day cycle for 3 cycles, followed by surgery'''<br />
<br />
===References===<br />
# Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, Basso U, Blay JY, Tendero O, Beveridge RD, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Donati DM, Palassini E, Palmerini E, De Sanctis R, Morosi C, Stacchiotti S, Bagué S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017 Jun;18(6):812-822. Epub 2017 May 9. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30334-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28499583 PubMed]<br />
<br />
=Locally advanced or metastatic disease, single-agent regimens=<br />
<br />
==Cisplatin monotherapy {{#subobject:6e93fa|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:2ff0fe|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70102-6/fulltext Blay et al. 2015]<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Cisplatin & Ombrabulin<br />
| style="background-color:#fc8d59" |Seems to have inferior PFS<br />
|-<br />
|}<br />
''Note: PFS was very poor in both groups (less than 2 months); the difference was not considered clinically meaningful.''<br />
====Chemotherapy====<br />
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1<br />
<br />
'''21-day cycles'''<br />
===References===<br />
# Blay JY, Pápai Z, Tolcher AW, Italiano A, Cupissol D, López-Pousa A, Chawla SP, Bompas E, Babovic N, Penel N, Isambert N, Staddon AP, Saâda-Bouzid E, Santoro A, Franke FA, Cohen P, Le-Guennec S, Demetri GD. Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015 May;16(5):531-40. Epub 2015 Apr 8. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70102-6/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25864104 PubMed]<br />
<br />
==Dacarbazine monotherapy {{#subobject:62426f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Variant #1, 850 mg/m<sup>2</sup> {{#subobject:f09c3f|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Eribulin_monotherapy|Eribulin]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Dacarbazine (DTIC)]] 850 mg/m<sup>2</sup> IV over 20 to 120 minutes once on day 1<br />
<br />
'''21-day cycles'''<br />
<br />
===Variant #2, 1000 mg/m<sup>2</sup> {{#subobject:4b5552|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ Demetri et al. 2015]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Trabectedin_monotherapy|Trabectedin]]<br />
| style="background-color:#d73027" |Inferior PFS<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Eribulin_monotherapy|Eribulin]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|}<br />
''Note: this is listed as a "starting dose" in '''Demetri et al. 2015''', but no adjustment instructions were provided in the manuscript.''<br />
====Chemotherapy====<br />
*[[Dacarbazine (DTIC)]] 1000 mg/m<sup>2</sup> IV over 20 to 120 minutes once on day 1<br />
<br />
'''21-day cycles'''<br />
<br />
===Variant #3, 1200 mg/m<sup>2</sup> {{#subobject:2c183b|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://annonc.oxfordjournals.org/content/2/4/307.long Buesa et al. 1991]<br />
| style="background-color:#91cf61" |Phase II<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[http://ascopubs.org/doi/full/10.1200/JCO.2010.33.6107 García-Del-Muro et al. 2011]<br />
| style="background-color:#1a9851" |Randomized phase II<br />
|[[#Dacarbazine_.26_Gemcitabine|Dacarbazine & Gemcitabine]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Eribulin_monotherapy|Eribulin]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Dacarbazine (DTIC)]] 1200 mg/m<sup>2</sup> IV over 20 minutes once on day 1<br />
<br />
====Supportive medications====<br />
*'''Buesa et al. 1991:''' Calcium gluconate (10% solution) 5 mL IV every 10 minutes x 3 doses (total of 15 mL) after the start of dacarbazine; 2 additional doses of calcium gluconate (10% solution) 5 mL IV every 10 minutes were given to patients whose systolic blood pressure decreased below 80 mmHg or heart rate more than 160 bpm.<br />
<br />
'''21-day cycles'''<br />
<br />
===References===<br />
# Buesa JM, Mouridsen HT, van Oosterom AT, Verweij J, Wagener T, Steward W, Poveda A, Vestlev PM, Thomas D, Sylvester R. High-dose DTIC in advanced soft-tissue sarcomas in the adult. A phase II study of the E.O.R.T.C. Soft Tissue and Bone Sarcoma Group. Ann Oncol. 1991 Apr;2(4):307-9. [http://annonc.oxfordjournals.org/content/2/4/307.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1868027 PubMed]<br />
# García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. [http://ascopubs.org/doi/full/10.1200/JCO.2010.33.6107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21606430 PubMed]<br />
# Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. [http://jco.ascopubs.org/content/34/8/786.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26371143 PubMed]<br />
## '''Subgroup analysis:''' Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. [https://www.ncbi.nlm.nih.gov/pubmed/28651804 PubMed]<br />
# Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26874885 PubMed]<br />
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [http://ascopubs.org/doi/full/10.1200/JCO.2016.71.6605 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28854066 PubMed]<br />
<br />
==Doxorubicin monotherapy {{#subobject:826f82|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:62faa6|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.ejcancer.com/article/0277-5379(87)90089-7/fulltext Mouridsen et al. 1987]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Epirubicin_monotherapy|Epirubicin]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
| rowspan="2" |[http://jco.ascopubs.org/content/25/21/3144.long Lorigan et al. 2007]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Ifosfamide_monotherapy|Ifos 3]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[[Soft tissue sarcoma#Ifosfamide_monotherapy|Ifos 9]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70063-4/abstract Judson et al. 2014 (EORTC 62012)]<br />
| style="background-color:#1a9851" |Phase III<br />
|Intensified Doxorubicin & Ifosfamide<br />
| style="background-color:#fee08b" |Might have inferior OS<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30587-6/fulltext Tap et al. 2016]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Doxorubicin_.26_Olaratumab|Doxorubicin & Olaratumab]]<br />
| style="background-color:#d73027" |Inferior OS<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30381-9/fulltext Tap et al. 2017 (TH CR-406/SARC021)]<br />
| style="background-color:#1a9851" |Phase III<br />
|Doxorubicin & Evofosfamide<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ Seddon et al. 2017 (GeDDiS)]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Docetaxel_.26_Gemcitabine|Docetaxel & Gemcitabine]]<br />
| style="background-color:#d9ef8b" |Might have superior PFS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV bolus once on day 1<br />
<br />
====Supportive medications====<br />
*In Tap et al. 2016, [[Dexrazoxane (Zinecard)]] (dose not specified) could be used on day 1 of every cycle to reduce the potential for doxorubicin-related cardiotoxicity in cycles 5 to 8<br />
<br />
'''21-day cycle for up to 6 to 8 cycles, until progression of disease, unacceptable toxicity, or patient refusal''' <br />
<br />
''Note: in '''Mouridsen et al. 1987''', treatment was given until progression of disease, unacceptable toxicity, or cumulative doxorubicin dosage of 550 mg/m<sup>2</sup>, though the ultimate decision to stop treatment based on cumulative doxorubicin dosage was at the discretion of the treating physician.''<br />
<br />
===References===<br />
# Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D et al. Adriamycin versus epirubicin in advanced soft tissue sarcomas. A randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. [http://www.ejcancer.com/article/0277-5379(87)90089-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3479329 PubMed]<br />
# '''Meta-analysis''' Bramwell VH, Anderson D, Charette ML. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: a meta-analysis and clinical practice guideline. Sarcoma. 2000;4(3):103-12. [http://www.hindawi.com/journals/srcm/2000/149793/abs/ link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2395439/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18521288 PubMed]<br />
# Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. [http://jco.ascopubs.org/content/25/21/3144.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17634494 PubMed]<br />
# Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay JY, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, Krarup-Hansen A, Alcindor T, Marreaud S, Litière S, Hermans C, Fisher C, Hogendoorn PC, dei Tos AP, van der Graaf WT; European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014 Apr;15(4):415-23. Epub 2014 Mar 5. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70063-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24618336 PubMed]<br />
# Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30587-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27291997 PubMed]<br />
# Tap WD, Papai Z, Van Tine BA, Attia S, Ganjoo KN, Jones RL, Schuetze S, Reed D, Chawla SP, Riedel RF, Krarup-Hansen A, Toulmonde M, Ray-Coquard I, Hohenberger P, Grignani G, Cranmer LD, Okuno S, Agulnik M, Read W, Ryan CW, Alcindor T, Del Muro XFG, Budd GT, Tawbi H, Pearce T, Kroll S, Reinke DK, Schöffski P. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1089-1103. Epub 2017 Jun 23. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30381-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28651927 PubMed]<br />
# Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30622-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28882536 PubMed]<br />
<br />
==Epirubicin monotherapy {{#subobject:d976a5|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:a1dd30|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.sciencedirect.com/science/article/pii/0277537987900897 Mouridsen et al. 1987]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Doxorubicin_monotherapy|Doxorubicin]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV bolus once on day 1<br />
<br />
'''21-day cycles, given until progression of disease, unacceptable toxicity, or cumulative epirubicin dosage of 550 mg/m<sup>2</sup>''' (though the ultimate decision to stop treatment based on cumulative epirubicin dosage was at the discretion of the treating physician)<br />
<br />
===References===<br />
# Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D et al. Adriamycin versus epirubicin in advanced soft tissue sarcomas. A randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. [http://www.sciencedirect.com/science/article/pii/0277537987900897 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3479329 PubMed]<br />
<br />
==Eribulin monotherapy {{#subobject:427859|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:2bcda0|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Dacarbazine_monotherapy|Dacarbazine]]<br />
| style="background-color:#91cf60" |Seems to have superior OS<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
<br />
'''21-day cycles until progression'''<br />
<br />
===References===<br />
# Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26874885 PubMed]<br />
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [http://ascopubs.org/doi/full/10.1200/JCO.2016.71.6605 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28854066 PubMed]<br />
<br />
==Ifosfamide monotherapy {{#subobject:88d059|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Variant #1, short infusion (Ifos 3) {{#subobject:89c8f1|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://jco.ascopubs.org/content/25/21/3144.long Lorigan et al. 2007]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Doxorubicin_monotherapy|Doxorubicin]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|Ifos 9<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3<br />
**Each day's dose of ifosfamide is mixed together with [[Mesna (Mesnex)]] in 1 liter of normal saline<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] as follows:<br />
**600 mg/m<sup>2</sup> IV bolus once on day 1, '''given immediately prior to mesna/ifosfamide infusion''', then<br />
**1500 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3, given together with [[Ifosfamide (Ifex)]], then<br />
**1200 mg/m<sup>2</sup> IV two times per day on days 1 to 3, given at 4 and 8 hours after completion of ifosfamide and mesna<br />
***An alternative is to use oral mesna instead of intravenous: [[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup> PO two times per day on days 1 to 3, given at 2 and 6 hours after completion of ifosfamide and mesna<br />
*Sodium bicarbonate 150 mmol IV once per day on days 1 to 3<br />
*Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion<br />
<br />
'''21-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or patient refusal'''<br />
<br />
===Variant #2, continuous infusion (Ifos 9) {{#subobject:ad63a|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://jco.ascopubs.org/content/25/21/3144.long Lorigan et al. 2007]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Doxorubicin_monotherapy|Doxorubicin]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|Ifos 3<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours (total dose per cycle: 9000 mg/m<sup>2</sup>) on days 1 to 3, given together with mesna<br />
**Each day's dose is mixed together with mesna in 3 liters of normal saline<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] as follows:<br />
**600 mg/m<sup>2</sup> IV bolus once on day 1, immediately prior to mesna/ifosfamide infusion, then<br />
**3000 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours (total dose per cycle: 9000 mg/m<sup>2</sup>) on days 1 to 3, given together with [[Ifosfamide (Ifex)]], then<br />
**1800 mg/m<sup>2</sup> IV over 12 hours once on day 4, starting after completion of ifosfamide and mesna<br />
***An alternative is to use oral mesna instead of intravenous: [[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup> PO three times on day 4, given 0, 2, and 6 hours after completion of ifosfamide and mesna<br />
*Sodium bicarbonate 150 mmol IV once per day on days 1 to 3<br />
*Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion<br />
<br />
'''21-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or patient refusal'''<br />
<br />
===Variant #3 {{#subobject:210d2d|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.ejcancer.com/article/S0959-8049(02)00491-4/fulltext van Oosterom et al. 2002]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 3<br />
**Each day's dose is dissolved in 125 mL sterile water per 1000 mg of ifosfamide, mixed together with [[Mesna (Mesnex)]] in an additional 1 liter of dextrose/saline<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] as follows:<br />
**600 mg/m<sup>2</sup> IV bolus once on day 1, immediately prior to mesna/ifosfamide infusion, then<br />
**1500 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3, given together with [[Ifosfamide (Ifex)]], then<br />
**500 mg/m<sup>2</sup> IV two times per day on days 1 to 3, given at 4 and 8 hours after completion of ifosfamide and mesna<br />
*"[[:Category:Emesis_prevention|Antiemetics]] were prescribed according to local conventions"<br />
*1 liter of fluid PO two times per day on days 1 to 3, taken 4 and 8 hours after completion of ifosfamide and mesna<br />
<br />
'''21-day cycle for at least 2 cycles, except in cases of rapid disease progression; continued until disease progression or unacceptable toxicity or patient refusal'''<br />
<br />
===References===<br />
# van Oosterom AT, Mouridsen HT, Nielsen OS, Dombernowsky P, Krzemieniecki K, Judson I, Svancarova L, Spooner D, Hermans C, Van Glabbeke M, Verweij J; EORTC Soft Tissue and Bone Sarcoma Group. Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients. Eur J Cancer. 2002 Dec;38(18):2397-406 [http://www.ejcancer.com/article/S0959-8049(02)00491-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12460784 PubMed] content property of [http://hemonc.org HemOnc.org]<br />
# Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. [http://jco.ascopubs.org/content/25/21/3144.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17634494 PubMed]<br />
<br />
==Pazopanib monotherapy {{#subobject:644c8f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:332a64|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract van der Graaf et al. 2012 (PALETTE)]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Placebo|Placebo]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Pazopanib (Votrient)]] 800 mg PO once per day<br />
<br />
'''Given until progression of disease, unacceptable toxicity, withdrawal of consent, or death'''<br />
<br />
===References===<br />
# van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Sch?ffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. Epub 2012 May 16. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22595799 PubMed]<br />
<br />
==Placebo==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract van der Graaf et al. 2012 (PALETTE)]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Pazopanib_monotherapy|Pazopanib]]<br />
| style="background-color:#d73027" |Inferior PFS<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70098-7/fulltext Kawai et al. 2015]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Trabectedin_monotherapy|Trabectedin]]<br />
| style="background-color:#d73027" |Inferior PFS<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/fulltext Mir et al. 2016 (REGOSARC)]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Regorafenib_monotherapy|Regorafenib]]<br />
| style="background-color:#d73027" |Inferior PFS (*)<br />
|-<br />
|}<br />
<br />
''No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only. Note: reported efficacy in '''REGOSARC''' is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.''<br />
<br />
===References===<br />
# van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Sch?ffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. Epub 2012 May 16. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22595799 PubMed]<br />
# Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015 Apr;16(4):406-16. Epub 2015 Mar 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70098-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25795406 PubMed]<br />
# Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27751846 PubMed]<br />
<br />
==Regorafenib monotherapy {{#subobject:c9fc2c|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:b5ff4e|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/fulltext Mir et al. 2016 (REGOSARC)]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Placebo|Placebo]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
''Note: reported efficacy is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.''<br />
====Chemotherapy====<br />
*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21<br />
<br />
'''28-day cycles'''<br />
<br />
===References===<br />
# Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27751846 PubMed]<br />
<br />
==Temozolomide monotherapy {{#subobject:5929ed|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Variant #1 {{#subobject:63d3d8|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.11730/full Talbot et al. 2003]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> (doses rounded up if needed to next available dosage based on capsule doses) PO once on day 1, on an empty stomach; then 12 hours later, 90 mg/m<sup>2</sup> PO once every 12 hours x 9 doses (total of 10 doses per cycle) on days 1 to 5, on an empty stomach<br />
<br />
====Supportive medications====<br />
*[[:Category:Emesis_prevention|Antiemetics]] "prescribed as clinically indicated by the treating physician"<br />
<br />
'''28-day cycles, given until progression of disease or 1 year; patients on study could be reconsented to receive therapy beyond 1 year'''<br />
<br />
===Variant #2 {{#subobject:892d65|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.21384/full Garcia del Muro et al. 2005]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Temozolomide (Temodar)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 42 (6 weeks), with no food 1 hour before and after temozolomide doses<br />
**Initial dose used in the study was 75 mg/m<sup>2</sup>, but due to lack of toxicity, protocol was amended to use 100 mg/m<sup>2</sup> doses<br />
<br />
====Supportive medications====<br />
*"[[:Category:Emesis_prevention|Antiemetics]], mainly oral [[Metoclopramide (Reglan)]] and [[Ondansetron (Zofran)]], were prescribed as clinically indicated by the treating physician"<br />
<br />
'''9-week cycle for up to 3 cycles, progression of disease, or unacceptable toxicity'''<br />
<br />
===References===<br />
# Talbot SM, Keohan ML, Hesdorffer M, Orrico R, Bagiella E, Troxel AB, Taub RN. A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer. 2003 Nov 1;98(9):1942-6. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.11730/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14584078 PubMed]<br />
# Garcia del Muro X, Lopez-Pousa A, Martin J, Buesa JM, Martinez-Trufero J, Casado A, Poveda A, Cruz J, Bover I, Maurel J; Spanish Group for Research on Sarcomas. A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma: a study by the Spanish Group for Research on Sarcomas. Cancer. 2005 Oct 15;104(8):1706-12. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.21384/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16134177 PubMed]<br />
<br />
==Trabectedin monotherapy {{#subobject:cfc3ed|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Variant #1 {{#subobject:05c55d|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ Demetri et al. 2015]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Dacarbazine_monotherapy|Dacarbazine]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
''Note: this is listed as a "starting dose," but no adjustment instructions were provided in the manuscript.''<br />
====Chemotherapy====<br />
*[[Trabectedin (Yondelis)]] 1.5 mg/m<sup>2</sup> IV continuous infusion over 24 hours, starting on day 1<br />
<br />
====Supportive medications====<br />
*[[Dexamethasone (Decadron)]] 20 mg IV once prior to trabectedin<br />
<br />
'''21-day cycles'''<br />
<br />
===Variant #2 {{#subobject:33de2b|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70098-7/fulltext Kawai et al. 2015]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Placebo|Placebo]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Trabectedin (Yondelis)]] 1.2 mg/m<sup>2</sup> IV continuous infusion over 24 hours, starting on day 1<br />
<br />
'''21-day cycles'''<br />
<br />
===References===<br />
# Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gómez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. Epub 2009 Aug 3. [http://ascopubs.org/doi/full/10.1200/JCO.2008.21.0088 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19652065 PubMed]<br />
# Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015 Apr;16(4):406-16. Epub 2015 Mar 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70098-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25795406 PubMed]<br />
# Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. [http://jco.ascopubs.org/content/34/8/786.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26371143 PubMed]<br />
## '''Subgroup analysis:''' Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. [https://www.ncbi.nlm.nih.gov/pubmed/28651804 PubMed]<br />
<br />
=Locally advanced or metastatic disease, combination regimens=<br />
<br />
==Doxorubicin & Ifosfamide (AIM) {{#subobject:e28770|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
AIM: '''<u>A</u>'''driamycin (doxorubicin), '''<u>I</u>'''fosfamide, '''<u>M</u>'''esna<br />
<br />
===Variant #1, 5-day course, lower dose doxorubicin - AI 75/10 {{#subobject:9c1374|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=1998&issue=06000&article=00025&type=abstract Patel et al. 1998]<br />
| style="background-color:#ffffbe" |Pilot, <20 patients reported<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours on days 1 to 3 (total dose per cycle: 75 mg/m<sup>2</sup>) <br />
*[[Ifosfamide (Ifex)]] 2000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5 (total dose per cycle: 10,000 mg/m<sup>2</sup>)<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] 400 mg/m<sup>2</sup> IV once on day 1, given simultaneously with the first dose of [[Ifosfamide (Ifex)]]<br />
*[[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 6000 mg/m<sup>2</sup>)<br />
**Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate<br />
*If febrile neutropenia occurs, [[:Category:Granulocyte colony-stimulating factors|G-CSF]] is used in subsequent cycles <br />
<br />
'''21-day cycles, given until maximum response, 6 cycles of therapy, progression of disease, or unacceptable toxicity'''<br />
<br />
===Variant #2, 4-day course, higher dose doxorubicin - AI 90/10 {{#subobject:2fd91c|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=1998&issue=06000&article=00025&type=abstract Patel et al. 1998]<br />
| style="background-color:#ffffbe" |Pilot, <20 patients reported<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours on days 1 to 3 (total dose per cycle: 90 mg/m<sup>2</sup>) <br />
*[[Ifosfamide (Ifex)]] 2500 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 4 (total dose per cycle: 10,000 mg/m<sup>2</sup>)<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] 500 mg/m<sup>2</sup> IV once on day 1, given simultaneously with the first dose of [[Ifosfamide (Ifex)]]<br />
*[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion over 4 days on days 1 to 4 (total dose per cycle: 6000 mg/m<sup>2</sup>)<br />
**Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate<br />
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 5 mcg/kg (dose rounded to 300 or 480 mcg) SC once per day, starting on day 5, given until ANC is at least 10,000/uL<br />
<br />
'''21-day cycles, given until maximum response, 6 cycles of therapy, progression of disease, or unacceptable toxicity'''<br />
<br />
=== Variant #3, 3-day course, lower dose doxorubicin and ifosfamide (COG ARST0332 Arm D, NCT00346164){{#subobject:2fd91c|Variant=1}} ===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://ascopubs.org/doi/abs/10.1200/jco.2015.33.15_suppl.10012 Venkatramani et al. 2015]<br />
| style="background-color:#91cf61" |Non-randomized prospective trial, minimum 20 patients<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 37.5 mg/m<sup>2</sup>/day (maximum 75 mg/dose) IV continuous infusion over 24 hours on days 1 and 2 (total dose per cycle: 75 mg/m<sup>2</sup>)<br />
**Given only 5 out of 6 cycles, for a total regimen dose of 375 mg/m<sup>2</sup>. <br />
**[[Doxorubicin (Adriamycin)]] doses are held when patients are receiving concurrent radiation therapy (for example, held during cycles 2 and 3, if radiation therapy is initiated with cycle 2). The missed doses are then administered in a different cycle, to maintain a total regimen dose of 375 mg/m<sup>2</sup>. If doses are held in 2 of 6 cycles, a doxorubicin-only "Cycle 7" may be given 21 days following cycle 6. <br />
*[[Ifosfamide (Ifex)]] 3 g/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3 (total dose per cycle: 9 g/m<sup>2</sup>)<br />
**Given all 6 cycles, for a total regimen dose of 54 g/m<sup>2</sup>.<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup> IV over 15 minutes given at 15 minutes before each dose of [[Ifosfamide (Ifex)]], then at 3 hours, 6 hours, and 9 hours after start of [[Ifosfamide (Ifex)]]<br />
*Hydration:<br />
**Before first [[Ifosfamide (Ifex)]] infusion: D5 1/2 NS IV at rate of 200 mL/m<sup>2</sup>/hr IV until urine output > 2 cc/kg/hr<br />
**With [[Ifosfamide (Ifex)]] infusion: D5 1/2 NS with 10 mEq KCL/L IV at rate of 125 mL/m<sup>2</sup>/hr IV beginning immediately after ifosfamide infusion and continuing until next ifosfamide dose, or until 24 hours after last dose.<br />
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 5 mcg/kg (max 480 mcg) SC once per day, starting on day 4, given until ANC is at least 2,000/uL after nadir. Filgrastim should not be administered within 24 hours of chemotherapy.<br />
<br />
'''21-day cycles, given until 6 cycles of therapy, progression of disease, or unacceptable toxicity'''<br />
<br />
==== Radiotherapy ====<br />
* Beginning with cycle 2 (week 4)<br />
* Doxorubicin is held for cycles which occur while receiving radiation therapy. <br />
<br />
==== Surgery ====<br />
* Definitive resection of primary tumor after recovery from cycle 3 (week 13)<br />
* Definitive resection of residual metastasis after completion of chemotherapy<br />
<br />
===References===<br />
# Patel SR, Vadhan-Raj S, Burgess MA, Plager C, Papadopolous N, Jenkins J, Benjamin RS. Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Am J Clin Oncol. 1998 Jun;21(3):317-21. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=1998&issue=06000&article=00025&type=abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9626808 PubMed]<br />
# Venkatramani R, Anderson JR, Million L, Coffin CM, McCarville B, Randall RL, et al. Risk-based treatment for synovial sarcoma in patients under 30 years of age: Children’s Oncology Group study ARST0332. J Clin Oncol [Internet]. 2015;33(15). [http://ascopubs.org/doi/abs/10.1200/jco.2015.33.15_suppl.10012 link to original abstract] '''contains protocol'''<br />
<br />
==Dacarbazine & Gemcitabine {{#subobject:cd9068|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:9aaddf|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://ascopubs.org/doi/full/10.1200/JCO.2010.33.6107 García-Del-Muro et al. 2011]<br />
| style="background-color:#1a9851" |Randomized phase II<br />
|[[#Dacarbazine_monotherapy|Dacarbazine]]<br />
| style="background-color:#91cf60" |Seems to have superior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Dacarbazine (DTIC)]] 500 mg/m<sup>2</sup> IV over 20 minutes once on day 1, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 1800 mg/m<sup>2</sup> IV over 3 hours (fixed-dose rate) once on day 1, '''given first'''<br />
<br />
'''14-day cycle for 12 cycles, or longer per clinician discretion'''<br />
<br />
===References===<br />
# García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. [http://ascopubs.org/doi/full/10.1200/JCO.2010.33.6107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21606430 PubMed]<br />
<br />
==Docetaxel & Gemcitabine {{#subobject:1e718f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Variant #1, 60/675 {{#subobject:270ac9|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;"<br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372854/ Hensley et al. 2015 (GOG-250)]<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Docetaxel, Gemcitabine, Bevacizumab<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
''This regimen was intended for patients who received prior radiation.''<br />
====Chemotherapy====<br />
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 675 mg/m<sup>2</sup> IV over 70 to 90 minutes once per day on days 1 & 8, '''given first'''<br />
<br />
'''21-day cycles''' <br />
<br />
===Variant #2, 75/675 {{#subobject:2898f9|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://jco.ascopubs.org/content/20/12/2824.long Hensley et al. 2002]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen was intended for patients who received prior radiation.''<br />
====Chemotherapy====<br />
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 675 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8, '''given first'''<br />
<br />
====Supportive medications====<br />
*[[Dexamethasone (Decadron)]] 8 mg PO BID on days 7-9 (the day before, the day of, and day after [[Docetaxel (Taxotere)]])<br />
*Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel<br />
*One of the following growth factors (varies depending on reference):<br />
**[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 150 mcg/m<sup>2</sup> (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements<br />
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on either day 9 or 10 (only one dose given)<br />
<br />
'''21-day cycle for 6 to 8 cycles'''; Hensley et al. 2008 did not specify a maximum number of cycles<br />
<br />
===Variant #3, 75/900 {{#subobject:2a13c9|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;"<br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372854/ Hensley et al. 2015 (GOG-250)]<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Docetaxel, Gemcitabine, Bevacizumab<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
''This regimen was intended for patients with no prior radiation.''<br />
====Chemotherapy====<br />
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 900 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8, '''given first'''<br />
<br />
'''21-day cycles''' <br />
<br />
===Variant #3, 100/900 {{#subobject:d89e30|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://jco.ascopubs.org/content/20/12/2824.long Hensley et al. 2002]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen was intended for patients with no prior radiation.''<br />
====Chemotherapy====<br />
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 900 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8, '''given first'''<br />
<br />
====Supportive medications====<br />
*[[Dexamethasone (Decadron)]] 8 mg PO BID on days 7 to 9 (the day before, the day of, and day after [[Docetaxel (Taxotere)]])<br />
*Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel<br />
*One of the following growth factors (varies depending on reference):<br />
**[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 150 mcg/m<sup>2</sup> (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements<br />
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on either day 9 or 10 (only one dose given)<br />
<br />
'''21-day cycle for 6 to 8 cycles'''; Hensley et al. 2008 did not specify a maximum number of cycles<br />
<br />
===References===<br />
# Hensley ML, Maki R, Venkatraman E, Geller G, Lovegren M, Aghajanian C, Sabbatini P, Tong W, Barakat R, Spriggs DR. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. 2002 Jun 15;20(12):2824-31. [http://jco.ascopubs.org/content/20/12/2824.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12065559 PubMed]<br />
# Hensley ML, Blessing JA, Mannel R, Rose PG. Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 2008 Jun;109(3):329-34. [http://www.gynecologiconcology-online.net/article/S0090-8258(08)00204-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504727/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18534250 PubMed]<br />
# '''GOG-250:''' Hensley ML, Miller A, O'Malley DM, Mannel RS, Behbakht K, Bakkum-Gamez JN, Michael H. Randomized phase III trial of gemcitabine plus docetaxel plus bevacizumab or placebo as first-line treatment for metastatic uterine leiomyosarcoma: an NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol. 2015 Apr 1;33(10):1180-5. Epub 2015 Feb 23. [http://ascopubs.org/doi/full/10.1200/JCO.2014.58.3781 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372854/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25713428 PubMed]<br />
# '''GeDDiS:''' Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30622-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28882536 PubMed]<br />
<br />
==Doxorubicin & Olaratumab {{#subobject:31132d|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:24a882|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30587-6/fulltext Tap et al. 2016]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Doxorubicin_monotherapy|Doxorubicin]]<br />
| style="background-color:#1a9850" |Superior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] as follows:<br />
**Cycles 1 to 8: 75 mg/m<sup>2</sup> IV once on day 1<br />
*[[Olaratumab (Lartruvo)]] 15 mg/kg IV once per day on days 1 & 8<br />
<br />
'''21-day cycles''' <br />
<br />
====Supportive medications====<br />
*In Tap et al. 2016, [[Dexrazoxane (Zinecard)]] (dose not specified) could be used on day 1 of every cycle to reduce the potential for doxorubicin-related cardiotoxicity in cycles 5 to 8<br />
<br />
===References===<br />
# Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. Epub 2016 Jun 9. Erratum in: Lancet. 2016 Jul 30;388(10043):464. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30587-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27291997 PubMed]<br />
<br />
==Epirubicin & Ifosfamide {{#subobject:820f20|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:55e5db|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://jco.ascopubs.org/content/16/4/1438.long Reichardt et al. 1998]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Epirubicin (Ellence)]] 45 mg/m<sup>2</sup>/day IV continuous infusion over 2 days on days 2 & 3 (total dose per cycle: 90 mg/m<sup>2</sup>)<br />
*[[Ifosfamide (Ifex)]] 2500 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 12,500 mg/m<sup>2</sup>)<br />
**Each day's dose is mixed together with [[Mesna (Mesnex)]] in 3 liters of "fluids with electrolytes"<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup> IV continuous infusion over 5 days on days 1 to 5, given together with [[Ifosfamide (Ifex)]] (total dose per cycle: 7500 mg/m<sup>2</sup>) <br />
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 5 mcg/kg SC once per day on days 6 to 15 or "until recovery of leukocytes"<br />
*[[Ondansetron (Zofran)]] 8-24 mg per day prn nausea<br />
*[[Dexamethasone (Decadron)]] (dose/schedule not specified) for antiemesis if necessary<br />
<br />
'''21-day cycles'''<br />
<br />
===References===<br />
# Reichardt P, Tilgner J, Hohenberger P, D?rken B. Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study. J Clin Oncol. 1998 Apr;16(4):1438-43. [http://jco.ascopubs.org/content/16/4/1438.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9552049 PubMed]<br />
<br />
==Gemcitabine & Vinorelbine {{#subobject:4dd538|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:b605f7|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.22609/full Dileo et al. 2007]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8<br />
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1 & 8<br />
<br />
'''21-day cycles'''<br />
<br />
===Reference===<br />
# Dileo P, Morgan JA, Zahrieh D, Desai J, Salesi JM, Harmon DC, Quigley MT, Polson K, Demetri GD, George S. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer. 2007 May 1;109(9):1863-9. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.22609/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17385194 PubMed]<br />
<br />
=Liposarcoma, all lines of therapy=<br />
''Note: this will be moved to a histology-specific page, shortly.''<br />
==Eribulin monotherapy {{#subobject:427859|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:2bcda0|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Dacarbazine_monotherapy|Dacarbazine]]<br />
| style="background-color:#1a9850" |Superior OS (*)<br />
|-<br />
|}<br />
''Efficacy is based on the 2017 subgroup analysis.''<br />
====Chemotherapy====<br />
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
<br />
'''21-day cycles until progression'''<br />
<br />
===References===<br />
# Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26874885 PubMed]<br />
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [http://ascopubs.org/doi/full/10.1200/JCO.2016.71.6605 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28854066 PubMed]<br />
<br />
=Rhabdomyosarcoma, all lines of therapy=<br />
''Note: this will be moved to a histology-specific page, shortly.''<br />
==VAC {{#subobject:4f2267|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VAC: '''<u>V</u>'''incristine, '''<u>A</u>'''ctinomycin D, '''<u>C</u>'''yclophosphamide<br />
===Regimen {{#subobject:060d90|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 Crist et al. 2001 (IRS-IV)]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[#VAI|VAI]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[[#VIE|VIE]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
To be completed<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]]<br />
*[[Dactinomycin (Cosmegen)]]<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
<br />
===References===<br />
# Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091-102. [http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11408506 PubMed]<br />
<br />
==VAI {{#subobject:9ab538|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VAI: '''<u>V</u>'''incristine, '''<u>A</u>'''ctinomycin D, '''<u>I</u>'''fosfamide<br />
<br>IVA: '''<u>I</u>'''fosfamide, '''<u>V</u>'''incristine, '''<u>A</u>'''ctinomycin D<br />
===Regimen {{#subobject:49f6c6|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 Crist et al. 2001 (IRS-IV)]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[#VAC|VAC]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[[#VIE|VIE]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[http://ascopubs.org/doi/full/10.1200/JCO.2011.40.3287 Oberlin et al. 2012 (SIOP MMT95)]<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|IVA/CEV/IVE<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
To be completed<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]]<br />
*[[Dactinomycin (Cosmegen)]]<br />
*[[Ifosfamide (Ifex)]]<br />
<br />
===References===<br />
# Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091-102. [http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11408506 PubMed]<br />
# Oberlin O, Rey A, Sanchez de Toledo J, Martelli H, Jenney ME, Scopinaro M, Bergeron C, Merks JH, Bouvet N, Ellershaw C, Kelsey A, Spooner D, Stevens MC. Randomized comparison of intensified six-drug versus standard three-drug chemotherapy for high-risk nonmetastatic rhabdomyosarcoma and other chemotherapy-sensitive childhood soft tissue sarcomas: long-term results from the International Society of Pediatric Oncology MMT95 study. J Clin Oncol. 2012 Jul 10;30(20):2457-65. Epub 2012 Jun 4. [http://ascopubs.org/doi/full/10.1200/JCO.2011.40.3287 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22665534 PubMed]<br />
<br />
==VI, then VDC/IE, then VAC, then VI {{#subobject:e080ff|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VI, then VDC/IE, then VAC, then VI: '''<u>V</u>'''incristine & '''<u>I</u>'''rinotecan, followed by '''<u>V</u>'''incristine, '''<u>D</u>'''oxorubicin, '''<u>C</u>'''yclophosphamide alternating with '''<u>I</u>'''fosfamide & '''<u>E</u>'''toposide, followed by '''<u>V</u>'''incristine, '''<u>A</u>'''ctinomycin D, '''<u>C</u>'''yclophosphamide, followed by '''<u>V</u>'''incristine & '''<u>I</u>'''rinotecan<br />
===Regimen {{#subobject:9a3f8d|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070550/ Weigel et al. 2015 (COG ARST0431)]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''Note: this is a complicated 54-week regimen with no immediate plans to add it to HemOnc.org. Please refer to the original article.''<br />
===References===<br />
# Weigel BJ, Lyden E, Anderson JR, Meyer WH, Parham DM, Rodeberg DA, Michalski JM, Hawkins DS, Arndt CA. Intensive multiagent therapy, including dose-compressed cycles of ifosfamide/etoposide and vincristine/doxorubicin/cyclophosphamide, irinotecan, and radiation, in patients with high-risk rhabdomyosarcoma: A report from the Children's Oncology Group. J Clin Oncol. 2016 Jan 10;34(2):117-22. Epub 2015 Oct 26. [http://ascopubs.org/doi/full/10.1200/JCO.2015.63.4048 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070550/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26503200 PubMed]<br />
<br />
==VIE {{#subobject:1b4037|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VIE: '''<u>V</u>'''incristine, '''<u>I</u>'''fosfamide, '''<u>E</u>'''toposide<br />
===Regimen {{#subobject:f0d233|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 Crist et al. 2001 (IRS-IV)]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[#VAC|VAC]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[[#VAI|VAI]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
To be completed<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]]<br />
*[[Ifosfamide (Ifex)]]<br />
*[[Etoposide (Vepesid)]]<br />
<br />
===References===<br />
# Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091-102. [http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11408506 PubMed]<br />
<br />
=Gastrointestinal stromal tumor (GIST), all lines of therapy=<br />
''Please see the [[Gastrointestinal stromal tumor|dedicated GIST page]].''<br />
<br />
[[Category:Soft tissue sarcoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Soft tissue sarcomas]]</div>Waynelianghttps://hemonc.org/w/index.php?title=Soft_tissue_sarcoma&diff=26005Soft tissue sarcoma2018-04-05T14:58:49Z<p>Wayneliang: /* AIM */ Added COG ARST0332 protocol for NRSTS</p>
<hr />
<div><!--'''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]]. If this is your first time visiting, we suggest you read the [[tutorial]].'''--><br />
<br />
<!--Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]].-->{| class="wikitable" style="text-align:center; width:50%;"<br />
! colspan="2" align="center" style="color:white; font-size:125%; background-color:#08519c" |'''Section editor'''<br />
|-<br />
| style="background-color:#F0F0F0" |[[File:jim_chen.jpeg|frameless|upright=0.3|center]]<br />
|<big>[[User:Jimchen|James L. Chen, MD, MS]]<br>Columbus, OH</big><br>[https://www.linkedin.com/in/jameschen777/ LinkedIn]<br />
|-<br />
|}<br />
{| class="wikitable" style="float:right; margin-right: 5px;"<br />
|-<br />
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div><br />
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div><br />
|}<br />
{{TOC limit|limit=3}}<br />
<big>Note: this page is for subtype-nonspecific soft tissue sarcoma regimens, as well as for sarcomas that are not readily categorized, e.g., alveolar soft part sarcoma. Please see the [[:Category:Soft tissue sarcomas|category page]] for links to other sarcoma types.</big><br />
=Guidelines=<br />
==[http://www.esmo.org/ ESMO]==<br />
*'''2014:''' [http://annonc.oxfordjournals.org/content/25/suppl_3/iii102.full.pdf+html Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/25210080 PubMed]<br />
<br />
==[https://www.nccn.org/ NCCN]==<br />
*[https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf NCCN Guidelines - Soft Tissue Sarcoma]<br />
<br />
=Neoadjuvant therapy=<br />
==Epirubicin & Ifosfamide {{#subobject:eeb76b|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:aea2c8|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30334-0/fulltext Gronchi et al. 2017 (ISG-STS 1001)]<br />
| style="background-color:#1a9851" |Phase III<br />
|Histotype-tailored therapy<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2<br />
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 to 3<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] with [[Ifosfamide (Ifex)]]; abstract does not list dosage/schedule<br />
<br />
'''21-day cycle for 3 cycles, followed by surgery'''<br />
<br />
===References===<br />
# Gronchi A, Ferrari S, Quagliuolo V, Broto JM, Pousa AL, Grignani G, Basso U, Blay JY, Tendero O, Beveridge RD, Ferraresi V, Lugowska I, Merlo DF, Fontana V, Marchesi E, Donati DM, Palassini E, Palmerini E, De Sanctis R, Morosi C, Stacchiotti S, Bagué S, Coindre JM, Dei Tos AP, Picci P, Bruzzi P, Casali PG. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017 Jun;18(6):812-822. Epub 2017 May 9. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30334-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28499583 PubMed]<br />
<br />
=Locally advanced or metastatic disease, single-agent regimens=<br />
<br />
==Cisplatin monotherapy {{#subobject:6e93fa|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:2ff0fe|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70102-6/fulltext Blay et al. 2015]<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Cisplatin & Ombrabulin<br />
| style="background-color:#fc8d59" |Seems to have inferior PFS<br />
|-<br />
|}<br />
''Note: PFS was very poor in both groups (less than 2 months); the difference was not considered clinically meaningful.''<br />
====Chemotherapy====<br />
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1<br />
<br />
'''21-day cycles'''<br />
===References===<br />
# Blay JY, Pápai Z, Tolcher AW, Italiano A, Cupissol D, López-Pousa A, Chawla SP, Bompas E, Babovic N, Penel N, Isambert N, Staddon AP, Saâda-Bouzid E, Santoro A, Franke FA, Cohen P, Le-Guennec S, Demetri GD. Ombrabulin plus cisplatin versus placebo plus cisplatin in patients with advanced soft-tissue sarcomas after failure of anthracycline and ifosfamide chemotherapy: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015 May;16(5):531-40. Epub 2015 Apr 8. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70102-6/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25864104 PubMed]<br />
<br />
==Dacarbazine monotherapy {{#subobject:62426f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Variant #1, 850 mg/m<sup>2</sup> {{#subobject:f09c3f|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Eribulin_monotherapy|Eribulin]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Dacarbazine (DTIC)]] 850 mg/m<sup>2</sup> IV over 20 to 120 minutes once on day 1<br />
<br />
'''21-day cycles'''<br />
<br />
===Variant #2, 1000 mg/m<sup>2</sup> {{#subobject:4b5552|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ Demetri et al. 2015]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Trabectedin_monotherapy|Trabectedin]]<br />
| style="background-color:#d73027" |Inferior PFS<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Eribulin_monotherapy|Eribulin]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|}<br />
''Note: this is listed as a "starting dose" in '''Demetri et al. 2015''', but no adjustment instructions were provided in the manuscript.''<br />
====Chemotherapy====<br />
*[[Dacarbazine (DTIC)]] 1000 mg/m<sup>2</sup> IV over 20 to 120 minutes once on day 1<br />
<br />
'''21-day cycles'''<br />
<br />
===Variant #3, 1200 mg/m<sup>2</sup> {{#subobject:2c183b|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://annonc.oxfordjournals.org/content/2/4/307.long Buesa et al. 1991]<br />
| style="background-color:#91cf61" |Phase II<br />
| style="background-color:#d3d3d3" |<br />
| style="background-color:#d3d3d3" |<br />
|-<br />
|[http://ascopubs.org/doi/full/10.1200/JCO.2010.33.6107 García-Del-Muro et al. 2011]<br />
| style="background-color:#1a9851" |Randomized phase II<br />
|[[#Dacarbazine_.26_Gemcitabine|Dacarbazine & Gemcitabine]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Eribulin_monotherapy|Eribulin]]<br />
| style="background-color:#fc8d59" |Seems to have inferior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Dacarbazine (DTIC)]] 1200 mg/m<sup>2</sup> IV over 20 minutes once on day 1<br />
<br />
====Supportive medications====<br />
*'''Buesa et al. 1991:''' Calcium gluconate (10% solution) 5 mL IV every 10 minutes x 3 doses (total of 15 mL) after the start of dacarbazine; 2 additional doses of calcium gluconate (10% solution) 5 mL IV every 10 minutes were given to patients whose systolic blood pressure decreased below 80 mmHg or heart rate more than 160 bpm.<br />
<br />
'''21-day cycles'''<br />
<br />
===References===<br />
# Buesa JM, Mouridsen HT, van Oosterom AT, Verweij J, Wagener T, Steward W, Poveda A, Vestlev PM, Thomas D, Sylvester R. High-dose DTIC in advanced soft-tissue sarcomas in the adult. A phase II study of the E.O.R.T.C. Soft Tissue and Bone Sarcoma Group. Ann Oncol. 1991 Apr;2(4):307-9. [http://annonc.oxfordjournals.org/content/2/4/307.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1868027 PubMed]<br />
# García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. [http://ascopubs.org/doi/full/10.1200/JCO.2010.33.6107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21606430 PubMed]<br />
# Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. [http://jco.ascopubs.org/content/34/8/786.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26371143 PubMed]<br />
## '''Subgroup analysis:''' Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. [https://www.ncbi.nlm.nih.gov/pubmed/28651804 PubMed]<br />
# Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26874885 PubMed]<br />
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [http://ascopubs.org/doi/full/10.1200/JCO.2016.71.6605 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28854066 PubMed]<br />
<br />
==Doxorubicin monotherapy {{#subobject:826f82|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:62faa6|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.ejcancer.com/article/0277-5379(87)90089-7/fulltext Mouridsen et al. 1987]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Epirubicin_monotherapy|Epirubicin]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
| rowspan="2" |[http://jco.ascopubs.org/content/25/21/3144.long Lorigan et al. 2007]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Ifosfamide_monotherapy|Ifos 3]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[[Soft tissue sarcoma#Ifosfamide_monotherapy|Ifos 9]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70063-4/abstract Judson et al. 2014 (EORTC 62012)]<br />
| style="background-color:#1a9851" |Phase III<br />
|Intensified Doxorubicin & Ifosfamide<br />
| style="background-color:#fee08b" |Might have inferior OS<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30587-6/fulltext Tap et al. 2016]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Doxorubicin_.26_Olaratumab|Doxorubicin & Olaratumab]]<br />
| style="background-color:#d73027" |Inferior OS<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30381-9/fulltext Tap et al. 2017 (TH CR-406/SARC021)]<br />
| style="background-color:#1a9851" |Phase III<br />
|Doxorubicin & Evofosfamide<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ Seddon et al. 2017 (GeDDiS)]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Docetaxel_.26_Gemcitabine|Docetaxel & Gemcitabine]]<br />
| style="background-color:#d9ef8b" |Might have superior PFS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV bolus once on day 1<br />
<br />
====Supportive medications====<br />
*In Tap et al. 2016, [[Dexrazoxane (Zinecard)]] (dose not specified) could be used on day 1 of every cycle to reduce the potential for doxorubicin-related cardiotoxicity in cycles 5 to 8<br />
<br />
'''21-day cycle for up to 6 to 8 cycles, until progression of disease, unacceptable toxicity, or patient refusal''' <br />
<br />
''Note: in '''Mouridsen et al. 1987''', treatment was given until progression of disease, unacceptable toxicity, or cumulative doxorubicin dosage of 550 mg/m<sup>2</sup>, though the ultimate decision to stop treatment based on cumulative doxorubicin dosage was at the discretion of the treating physician.''<br />
<br />
===References===<br />
# Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D et al. Adriamycin versus epirubicin in advanced soft tissue sarcomas. A randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. [http://www.ejcancer.com/article/0277-5379(87)90089-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3479329 PubMed]<br />
# '''Meta-analysis''' Bramwell VH, Anderson D, Charette ML. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: a meta-analysis and clinical practice guideline. Sarcoma. 2000;4(3):103-12. [http://www.hindawi.com/journals/srcm/2000/149793/abs/ link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2395439/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18521288 PubMed]<br />
# Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. [http://jco.ascopubs.org/content/25/21/3144.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17634494 PubMed]<br />
# Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay JY, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, Krarup-Hansen A, Alcindor T, Marreaud S, Litière S, Hermans C, Fisher C, Hogendoorn PC, dei Tos AP, van der Graaf WT; European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014 Apr;15(4):415-23. Epub 2014 Mar 5. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70063-4/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24618336 PubMed]<br />
# Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30587-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27291997 PubMed]<br />
# Tap WD, Papai Z, Van Tine BA, Attia S, Ganjoo KN, Jones RL, Schuetze S, Reed D, Chawla SP, Riedel RF, Krarup-Hansen A, Toulmonde M, Ray-Coquard I, Hohenberger P, Grignani G, Cranmer LD, Okuno S, Agulnik M, Read W, Ryan CW, Alcindor T, Del Muro XFG, Budd GT, Tawbi H, Pearce T, Kroll S, Reinke DK, Schöffski P. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2017 Aug;18(8):1089-1103. Epub 2017 Jun 23. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30381-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28651927 PubMed]<br />
# Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30622-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28882536 PubMed]<br />
<br />
==Epirubicin monotherapy {{#subobject:d976a5|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:a1dd30|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.sciencedirect.com/science/article/pii/0277537987900897 Mouridsen et al. 1987]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Doxorubicin_monotherapy|Doxorubicin]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Epirubicin (Ellence)]] 75 mg/m<sup>2</sup> IV bolus once on day 1<br />
<br />
'''21-day cycles, given until progression of disease, unacceptable toxicity, or cumulative epirubicin dosage of 550 mg/m<sup>2</sup>''' (though the ultimate decision to stop treatment based on cumulative epirubicin dosage was at the discretion of the treating physician)<br />
<br />
===References===<br />
# Mouridsen HT, Bastholt L, Somers R, Santoro A, Bramwell V, Mulder JH, van Oosterom AT, Buesa J, Pinedo HM, Thomas D et al. Adriamycin versus epirubicin in advanced soft tissue sarcomas. A randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer Clin Oncol. 1987 Oct;23(10):1477-83. [http://www.sciencedirect.com/science/article/pii/0277537987900897 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3479329 PubMed]<br />
<br />
==Eribulin monotherapy {{#subobject:427859|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
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|}<br />
<br />
===Regimen {{#subobject:2bcda0|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Dacarbazine_monotherapy|Dacarbazine]]<br />
| style="background-color:#91cf60" |Seems to have superior OS<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
<br />
'''21-day cycles until progression'''<br />
<br />
===References===<br />
# Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26874885 PubMed]<br />
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [http://ascopubs.org/doi/full/10.1200/JCO.2016.71.6605 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28854066 PubMed]<br />
<br />
==Ifosfamide monotherapy {{#subobject:88d059|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
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|}<br />
<br />
===Variant #1, short infusion (Ifos 3) {{#subobject:89c8f1|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://jco.ascopubs.org/content/25/21/3144.long Lorigan et al. 2007]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Doxorubicin_monotherapy|Doxorubicin]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|Ifos 9<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3<br />
**Each day's dose of ifosfamide is mixed together with [[Mesna (Mesnex)]] in 1 liter of normal saline<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] as follows:<br />
**600 mg/m<sup>2</sup> IV bolus once on day 1, '''given immediately prior to mesna/ifosfamide infusion''', then<br />
**1500 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3, given together with [[Ifosfamide (Ifex)]], then<br />
**1200 mg/m<sup>2</sup> IV two times per day on days 1 to 3, given at 4 and 8 hours after completion of ifosfamide and mesna<br />
***An alternative is to use oral mesna instead of intravenous: [[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup> PO two times per day on days 1 to 3, given at 2 and 6 hours after completion of ifosfamide and mesna<br />
*Sodium bicarbonate 150 mmol IV once per day on days 1 to 3<br />
*Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion<br />
<br />
'''21-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or patient refusal'''<br />
<br />
===Variant #2, continuous infusion (Ifos 9) {{#subobject:ad63a|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://jco.ascopubs.org/content/25/21/3144.long Lorigan et al. 2007]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Doxorubicin_monotherapy|Doxorubicin]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|Ifos 3<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours (total dose per cycle: 9000 mg/m<sup>2</sup>) on days 1 to 3, given together with mesna<br />
**Each day's dose is mixed together with mesna in 3 liters of normal saline<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] as follows:<br />
**600 mg/m<sup>2</sup> IV bolus once on day 1, immediately prior to mesna/ifosfamide infusion, then<br />
**3000 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours (total dose per cycle: 9000 mg/m<sup>2</sup>) on days 1 to 3, given together with [[Ifosfamide (Ifex)]], then<br />
**1800 mg/m<sup>2</sup> IV over 12 hours once on day 4, starting after completion of ifosfamide and mesna<br />
***An alternative is to use oral mesna instead of intravenous: [[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup> PO three times on day 4, given 0, 2, and 6 hours after completion of ifosfamide and mesna<br />
*Sodium bicarbonate 150 mmol IV once per day on days 1 to 3<br />
*Patient with somnolence or other signs of encephalopathy with ifosfamide received methylene blue 50 mg IV every 4 hours until resolution of symptoms. During cycles thereafter, patients would receive methylene blue 50 mg IV every 4 hours, starting 4 hours prior to ifosfamide on day 1, continuing until 72 hours after completion<br />
<br />
'''21-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or patient refusal'''<br />
<br />
===Variant #3 {{#subobject:210d2d|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://www.ejcancer.com/article/S0959-8049(02)00491-4/fulltext van Oosterom et al. 2002]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV over 4 hours once per day on days 1 to 3<br />
**Each day's dose is dissolved in 125 mL sterile water per 1000 mg of ifosfamide, mixed together with [[Mesna (Mesnex)]] in an additional 1 liter of dextrose/saline<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] as follows:<br />
**600 mg/m<sup>2</sup> IV bolus once on day 1, immediately prior to mesna/ifosfamide infusion, then<br />
**1500 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3, given together with [[Ifosfamide (Ifex)]], then<br />
**500 mg/m<sup>2</sup> IV two times per day on days 1 to 3, given at 4 and 8 hours after completion of ifosfamide and mesna<br />
*"[[:Category:Emesis_prevention|Antiemetics]] were prescribed according to local conventions"<br />
*1 liter of fluid PO two times per day on days 1 to 3, taken 4 and 8 hours after completion of ifosfamide and mesna<br />
<br />
'''21-day cycle for at least 2 cycles, except in cases of rapid disease progression; continued until disease progression or unacceptable toxicity or patient refusal'''<br />
<br />
===References===<br />
# van Oosterom AT, Mouridsen HT, Nielsen OS, Dombernowsky P, Krzemieniecki K, Judson I, Svancarova L, Spooner D, Hermans C, Van Glabbeke M, Verweij J; EORTC Soft Tissue and Bone Sarcoma Group. Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients. Eur J Cancer. 2002 Dec;38(18):2397-406 [http://www.ejcancer.com/article/S0959-8049(02)00491-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12460784 PubMed] content property of [http://hemonc.org HemOnc.org]<br />
# Lorigan P, Verweij J, Papai Z, Rodenhuis S, Le Cesne A, Leahy MG, Radford JA, Van Glabbeke MM, Kirkpatrick A, Hogendoorn PC, Blay JY; European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 2007 Jul 20;25(21):3144-50. [http://jco.ascopubs.org/content/25/21/3144.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17634494 PubMed]<br />
<br />
==Pazopanib monotherapy {{#subobject:644c8f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:332a64|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract van der Graaf et al. 2012 (PALETTE)]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Placebo|Placebo]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Pazopanib (Votrient)]] 800 mg PO once per day<br />
<br />
'''Given until progression of disease, unacceptable toxicity, withdrawal of consent, or death'''<br />
<br />
===References===<br />
# van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Sch?ffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. Epub 2012 May 16. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22595799 PubMed]<br />
<br />
==Placebo==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract van der Graaf et al. 2012 (PALETTE)]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[Soft tissue sarcoma#Pazopanib_monotherapy|Pazopanib]]<br />
| style="background-color:#d73027" |Inferior PFS<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70098-7/fulltext Kawai et al. 2015]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Trabectedin_monotherapy|Trabectedin]]<br />
| style="background-color:#d73027" |Inferior PFS<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/fulltext Mir et al. 2016 (REGOSARC)]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Regorafenib_monotherapy|Regorafenib]]<br />
| style="background-color:#d73027" |Inferior PFS (*)<br />
|-<br />
|}<br />
<br />
''No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only. Note: reported efficacy in '''REGOSARC''' is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.''<br />
<br />
===References===<br />
# van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Sch?ffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. Epub 2012 May 16. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60651-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22595799 PubMed]<br />
# Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015 Apr;16(4):406-16. Epub 2015 Mar 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70098-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25795406 PubMed]<br />
# Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27751846 PubMed]<br />
<br />
==Regorafenib monotherapy {{#subobject:c9fc2c|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:b5ff4e|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/fulltext Mir et al. 2016 (REGOSARC)]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Placebo|Placebo]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
''Note: reported efficacy is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.''<br />
====Chemotherapy====<br />
*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21<br />
<br />
'''28-day cycles'''<br />
<br />
===References===<br />
# Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30507-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27751846 PubMed]<br />
<br />
==Temozolomide monotherapy {{#subobject:5929ed|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Variant #1 {{#subobject:63d3d8|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.11730/full Talbot et al. 2003]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> (doses rounded up if needed to next available dosage based on capsule doses) PO once on day 1, on an empty stomach; then 12 hours later, 90 mg/m<sup>2</sup> PO once every 12 hours x 9 doses (total of 10 doses per cycle) on days 1 to 5, on an empty stomach<br />
<br />
====Supportive medications====<br />
*[[:Category:Emesis_prevention|Antiemetics]] "prescribed as clinically indicated by the treating physician"<br />
<br />
'''28-day cycles, given until progression of disease or 1 year; patients on study could be reconsented to receive therapy beyond 1 year'''<br />
<br />
===Variant #2 {{#subobject:892d65|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.21384/full Garcia del Muro et al. 2005]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Temozolomide (Temodar)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 42 (6 weeks), with no food 1 hour before and after temozolomide doses<br />
**Initial dose used in the study was 75 mg/m<sup>2</sup>, but due to lack of toxicity, protocol was amended to use 100 mg/m<sup>2</sup> doses<br />
<br />
====Supportive medications====<br />
*"[[:Category:Emesis_prevention|Antiemetics]], mainly oral [[Metoclopramide (Reglan)]] and [[Ondansetron (Zofran)]], were prescribed as clinically indicated by the treating physician"<br />
<br />
'''9-week cycle for up to 3 cycles, progression of disease, or unacceptable toxicity'''<br />
<br />
===References===<br />
# Talbot SM, Keohan ML, Hesdorffer M, Orrico R, Bagiella E, Troxel AB, Taub RN. A phase II trial of temozolomide in patients with unresectable or metastatic soft tissue sarcoma. Cancer. 2003 Nov 1;98(9):1942-6. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.11730/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14584078 PubMed]<br />
# Garcia del Muro X, Lopez-Pousa A, Martin J, Buesa JM, Martinez-Trufero J, Casado A, Poveda A, Cruz J, Bover I, Maurel J; Spanish Group for Research on Sarcomas. A phase II trial of temozolomide as a 6-week, continuous, oral schedule in patients with advanced soft tissue sarcoma: a study by the Spanish Group for Research on Sarcomas. Cancer. 2005 Oct 15;104(8):1706-12. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.21384/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16134177 PubMed]<br />
<br />
==Trabectedin monotherapy {{#subobject:cfc3ed|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Variant #1 {{#subobject:05c55d|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ Demetri et al. 2015]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Dacarbazine_monotherapy|Dacarbazine]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
''Note: this is listed as a "starting dose," but no adjustment instructions were provided in the manuscript.''<br />
====Chemotherapy====<br />
*[[Trabectedin (Yondelis)]] 1.5 mg/m<sup>2</sup> IV continuous infusion over 24 hours, starting on day 1<br />
<br />
====Supportive medications====<br />
*[[Dexamethasone (Decadron)]] 20 mg IV once prior to trabectedin<br />
<br />
'''21-day cycles'''<br />
<br />
===Variant #2 {{#subobject:33de2b|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70098-7/fulltext Kawai et al. 2015]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Placebo|Placebo]]<br />
| style="background-color:#1a9850" |Superior PFS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Trabectedin (Yondelis)]] 1.2 mg/m<sup>2</sup> IV continuous infusion over 24 hours, starting on day 1<br />
<br />
'''21-day cycles'''<br />
<br />
===References===<br />
# Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gómez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. Epub 2009 Aug 3. [http://ascopubs.org/doi/full/10.1200/JCO.2008.21.0088 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19652065 PubMed]<br />
# Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015 Apr;16(4):406-16. Epub 2015 Mar 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70098-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25795406 PubMed]<br />
# Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. Epub 2015 Sep 14. [http://jco.ascopubs.org/content/34/8/786.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070559/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26371143 PubMed]<br />
## '''Subgroup analysis:''' Hensley ML, Patel SR, von Mehren M, Ganjoo K, Jones RL, Staddon A, Rushing D, Milhem M, Monk B, Wang G, McCarthy S, Knoblauch RE, Parekh TV, Maki RG, Demetri GD. Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial. Gynecol Oncol. 2017 Sep;146(3):531-537. Epub 2017 Jun 24. [https://www.ncbi.nlm.nih.gov/pubmed/28651804 PubMed]<br />
<br />
=Locally advanced or metastatic disease, combination regimens=<br />
<br />
==Doxorubicin & Ifosfamide (AIM) {{#subobject:e28770|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
AIM: '''<u>A</u>'''driamycin (doxorubicin), '''<u>I</u>'''fosfamide, '''<u>M</u>'''esna<br />
<br />
===Variant #1, 5-day course, lower dose doxorubicin - AI 75/10 {{#subobject:9c1374|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=1998&issue=06000&article=00025&type=abstract Patel et al. 1998]<br />
| style="background-color:#ffffbe" |Pilot, <20 patients reported<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours on days 1 to 3 (total dose per cycle: 75 mg/m<sup>2</sup>) <br />
*[[Ifosfamide (Ifex)]] 2000 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5 (total dose per cycle: 10,000 mg/m<sup>2</sup>)<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] 400 mg/m<sup>2</sup> IV once on day 1, given simultaneously with the first dose of [[Ifosfamide (Ifex)]]<br />
*[[Mesna (Mesnex)]] 1200 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 6000 mg/m<sup>2</sup>)<br />
**Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate<br />
*If febrile neutropenia occurs, [[:Category:Granulocyte colony-stimulating factors|G-CSF]] is used in subsequent cycles <br />
<br />
'''21-day cycles, given until maximum response, 6 cycles of therapy, progression of disease, or unacceptable toxicity'''<br />
<br />
===Variant #2, 4-day course, higher dose doxorubicin - AI 90/10 {{#subobject:2fd91c|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=1998&issue=06000&article=00025&type=abstract Patel et al. 1998]<br />
| style="background-color:#ffffbe" |Pilot, <20 patients reported<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours on days 1 to 3 (total dose per cycle: 90 mg/m<sup>2</sup>) <br />
*[[Ifosfamide (Ifex)]] 2500 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 4 (total dose per cycle: 10,000 mg/m<sup>2</sup>)<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] 500 mg/m<sup>2</sup> IV once on day 1, given simultaneously with the first dose of [[Ifosfamide (Ifex)]]<br />
*[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup>/day IV continuous infusion over 4 days on days 1 to 4 (total dose per cycle: 6000 mg/m<sup>2</sup>)<br />
**Each day's dose is given in 2 liters of D5W with 100 mEq/L sodium acetate, 20 mEq/L potassium acetate, and 4 mEq/L magnesium sulfate<br />
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 5 mcg/kg (dose rounded to 300 or 480 mcg) SC once per day, starting on day 5, given until ANC is at least 10,000/uL<br />
<br />
'''21-day cycles, given until maximum response, 6 cycles of therapy, progression of disease, or unacceptable toxicity'''<br />
<br />
=== Variant #3, 3-day course, lower dose doxorubicin and ifosfamide (COG ARST0332 Arm D, NCT00346164){{#subobject:2fd91c|Variant=1}} ===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://ascopubs.org/doi/abs/10.1200/jco.2015.33.15_suppl.10012 Venkatramani et al. 2015]<br />
| style="background-color:#ffffbe" |Non-randomized prospective trial, minimum 20 patients<br />
|-<br />
|}<br />
<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] 37.5 mg/m<sup>2</sup>/day (maximum 75 mg/dose) IV continuous infusion over 24 hours on days 1 and 2 (total dose per cycle: 75 mg/m<sup>2</sup>)<br />
**Given only 5 out of 6 cycles, for a total regimen dose of 375 mg/m<sup>2</sup>. <br />
**[[Doxorubicin (Adriamycin)]] doses are held when patients are receiving concurrent radiation therapy (for example, held during cycles 2 and 3, if radiation therapy is initiated with cycle 2). The missed doses are then administered in a different cycle, to maintain a total regimen dose of 375 mg/m<sup>2</sup>. If doses are held in 2 of 6 cycles, a doxorubicin-only "Cycle 7" may be given 21 days following cycle 6. <br />
*[[Ifosfamide (Ifex)]] 3 g/m<sup>2</sup> IV over 3 hours once per day on days 1 to 3 (total dose per cycle: 9 g/m<sup>2</sup>)<br />
**Given all 6 cycles, for a total regimen dose of 54 g/m<sup>2</sup>.<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup> IV over 15 minutes given at 15 minutes before each dose of [[Ifosfamide (Ifex)]], then at 3 hours, 6 hours, and 9 hours after start of [[Ifosfamide (Ifex)]]<br />
*Hydration:<br />
**Before first [[Ifosfamide (Ifex)]] infusion: D5 1/2 NS IV at rate of 200 mL/m<sup>2</sup>/hr IV until urine output > 2 cc/kg/hr<br />
**With [[Ifosfamide (Ifex)]] infusion: D5 1/2 NS with 10 mEq KCL/L IV at rate of 125 mL/m<sup>2</sup>/hr IV beginning immediately after ifosfamide infusion and continuing until next ifosfamide dose, or until 24 hours after last dose.<br />
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 5 mcg/kg (max 480 mcg) SC once per day, starting on day 4, given until ANC is at least 2,000/uL after nadir. Filgrastim should not be administered within 24 hours of chemotherapy.<br />
<br />
'''21-day cycles, given until 6 cycles of therapy, progression of disease, or unacceptable toxicity'''<br />
<br />
==== Radiotherapy ====<br />
* Beginning with cycle 2 (week 4)<br />
* Doxorubicin is held for cycles which occur while receiving radiation therapy. <br />
<br />
==== Surgery ====<br />
* Definitive resection of primary tumor after recovery from cycle 3 (week 13)<br />
* Definitive resection of residual metastasis after completion of chemotherapy<br />
<br />
===References===<br />
# Patel SR, Vadhan-Raj S, Burgess MA, Plager C, Papadopolous N, Jenkins J, Benjamin RS. Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Am J Clin Oncol. 1998 Jun;21(3):317-21. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=1998&issue=06000&article=00025&type=abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9626808 PubMed]<br />
# Venkatramani R, Anderson JR, Million L, Coffin CM, McCarville B, Randall RL, et al. Risk-based treatment for synovial sarcoma in patients under 30 years of age: Children’s Oncology Group study ARST0332. J Clin Oncol [Internet]. 2015;33(15). [http://ascopubs.org/doi/abs/10.1200/jco.2015.33.15_suppl.10012 link to original abstract] '''contains protocol'''<br />
<br />
==Dacarbazine & Gemcitabine {{#subobject:cd9068|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:9aaddf|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://ascopubs.org/doi/full/10.1200/JCO.2010.33.6107 García-Del-Muro et al. 2011]<br />
| style="background-color:#1a9851" |Randomized phase II<br />
|[[#Dacarbazine_monotherapy|Dacarbazine]]<br />
| style="background-color:#91cf60" |Seems to have superior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Dacarbazine (DTIC)]] 500 mg/m<sup>2</sup> IV over 20 minutes once on day 1, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 1800 mg/m<sup>2</sup> IV over 3 hours (fixed-dose rate) once on day 1, '''given first'''<br />
<br />
'''14-day cycle for 12 cycles, or longer per clinician discretion'''<br />
<br />
===References===<br />
# García-Del-Muro X, López-Pousa A, Maurel J, Martín J, Martínez-Trufero J, Casado A, Gómez-España A, Fra J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubió J, De Juan A, Laínez N, Carrasco JA, de Andrés R, Buesa JM; Spanish Group for Research on Sarcomas. Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study. J Clin Oncol. 2011 Jun 20;29(18):2528-33. Epub 2011 May 23. [http://ascopubs.org/doi/full/10.1200/JCO.2010.33.6107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21606430 PubMed]<br />
<br />
==Docetaxel & Gemcitabine {{#subobject:1e718f|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Variant #1, 60/675 {{#subobject:270ac9|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;"<br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372854/ Hensley et al. 2015 (GOG-250)]<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Docetaxel, Gemcitabine, Bevacizumab<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
''This regimen was intended for patients who received prior radiation.''<br />
====Chemotherapy====<br />
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 675 mg/m<sup>2</sup> IV over 70 to 90 minutes once per day on days 1 & 8, '''given first'''<br />
<br />
'''21-day cycles''' <br />
<br />
===Variant #2, 75/675 {{#subobject:2898f9|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://jco.ascopubs.org/content/20/12/2824.long Hensley et al. 2002]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen was intended for patients who received prior radiation.''<br />
====Chemotherapy====<br />
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 675 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8, '''given first'''<br />
<br />
====Supportive medications====<br />
*[[Dexamethasone (Decadron)]] 8 mg PO BID on days 7-9 (the day before, the day of, and day after [[Docetaxel (Taxotere)]])<br />
*Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel<br />
*One of the following growth factors (varies depending on reference):<br />
**[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 150 mcg/m<sup>2</sup> (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements<br />
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on either day 9 or 10 (only one dose given)<br />
<br />
'''21-day cycle for 6 to 8 cycles'''; Hensley et al. 2008 did not specify a maximum number of cycles<br />
<br />
===Variant #3, 75/900 {{#subobject:2a13c9|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;"<br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372854/ Hensley et al. 2015 (GOG-250)]<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|Docetaxel, Gemcitabine, Bevacizumab<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
''This regimen was intended for patients with no prior radiation.''<br />
====Chemotherapy====<br />
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 900 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8, '''given first'''<br />
<br />
'''21-day cycles''' <br />
<br />
===Variant #3, 100/900 {{#subobject:d89e30|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://jco.ascopubs.org/content/20/12/2824.long Hensley et al. 2002]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''This regimen was intended for patients with no prior radiation.''<br />
====Chemotherapy====<br />
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 8, '''given second'''<br />
*[[Gemcitabine (Gemzar)]] 900 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8, '''given first'''<br />
<br />
====Supportive medications====<br />
*[[Dexamethasone (Decadron)]] 8 mg PO BID on days 7 to 9 (the day before, the day of, and day after [[Docetaxel (Taxotere)]])<br />
*Patients could receive diuretics at physician discretion for peripheral edema related to docetaxel<br />
*One of the following growth factors (varies depending on reference):<br />
**[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 150 mcg/m<sup>2</sup> (dose rounded to 300 or 480 mcg) SC once per day on days 9 to 15 as primary neutropenia prophylaxis; could be stopped before day 15 if ANC greater than 1200/uL on two separate measurements<br />
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on either day 9 or 10 (only one dose given)<br />
<br />
'''21-day cycle for 6 to 8 cycles'''; Hensley et al. 2008 did not specify a maximum number of cycles<br />
<br />
===References===<br />
# Hensley ML, Maki R, Venkatraman E, Geller G, Lovegren M, Aghajanian C, Sabbatini P, Tong W, Barakat R, Spriggs DR. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. 2002 Jun 15;20(12):2824-31. [http://jco.ascopubs.org/content/20/12/2824.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12065559 PubMed]<br />
# Hensley ML, Blessing JA, Mannel R, Rose PG. Fixed-dose rate gemcitabine plus docetaxel as first-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II trial. Gynecol Oncol. 2008 Jun;109(3):329-34. [http://www.gynecologiconcology-online.net/article/S0090-8258(08)00204-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504727/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18534250 PubMed]<br />
# '''GOG-250:''' Hensley ML, Miller A, O'Malley DM, Mannel RS, Behbakht K, Bakkum-Gamez JN, Michael H. Randomized phase III trial of gemcitabine plus docetaxel plus bevacizumab or placebo as first-line treatment for metastatic uterine leiomyosarcoma: an NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol. 2015 Apr 1;33(10):1180-5. Epub 2015 Feb 23. [http://ascopubs.org/doi/full/10.1200/JCO.2014.58.3781 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372854/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25713428 PubMed]<br />
# '''GeDDiS:''' Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. Epub 2017 Sep 4. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30622-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622179/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28882536 PubMed]<br />
<br />
==Doxorubicin & Olaratumab {{#subobject:31132d|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:24a882|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30587-6/fulltext Tap et al. 2016]<br />
| style="background-color:#1a9851" |Randomized Phase II<br />
|[[#Doxorubicin_monotherapy|Doxorubicin]]<br />
| style="background-color:#1a9850" |Superior OS<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Doxorubicin (Adriamycin)]] as follows:<br />
**Cycles 1 to 8: 75 mg/m<sup>2</sup> IV once on day 1<br />
*[[Olaratumab (Lartruvo)]] 15 mg/kg IV once per day on days 1 & 8<br />
<br />
'''21-day cycles''' <br />
<br />
====Supportive medications====<br />
*In Tap et al. 2016, [[Dexrazoxane (Zinecard)]] (dose not specified) could be used on day 1 of every cycle to reduce the potential for doxorubicin-related cardiotoxicity in cycles 5 to 8<br />
<br />
===References===<br />
# Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R Jr, Conti I, Cosaert J, Schwartz GK. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016 Jul 30;388(10043):488-97. Epub 2016 Jun 9. Erratum in: Lancet. 2016 Jul 30;388(10043):464. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30587-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27291997 PubMed]<br />
<br />
==Epirubicin & Ifosfamide {{#subobject:820f20|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:55e5db|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://jco.ascopubs.org/content/16/4/1438.long Reichardt et al. 1998]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Epirubicin (Ellence)]] 45 mg/m<sup>2</sup>/day IV continuous infusion over 2 days on days 2 & 3 (total dose per cycle: 90 mg/m<sup>2</sup>)<br />
*[[Ifosfamide (Ifex)]] 2500 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 12,500 mg/m<sup>2</sup>)<br />
**Each day's dose is mixed together with [[Mesna (Mesnex)]] in 3 liters of "fluids with electrolytes"<br />
<br />
====Supportive medications====<br />
*[[Mesna (Mesnex)]] 1500 mg/m<sup>2</sup> IV continuous infusion over 5 days on days 1 to 5, given together with [[Ifosfamide (Ifex)]] (total dose per cycle: 7500 mg/m<sup>2</sup>) <br />
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] 5 mcg/kg SC once per day on days 6 to 15 or "until recovery of leukocytes"<br />
*[[Ondansetron (Zofran)]] 8-24 mg per day prn nausea<br />
*[[Dexamethasone (Decadron)]] (dose/schedule not specified) for antiemesis if necessary<br />
<br />
'''21-day cycles'''<br />
<br />
===References===<br />
# Reichardt P, Tilgner J, Hohenberger P, D?rken B. Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study. J Clin Oncol. 1998 Apr;16(4):1438-43. [http://jco.ascopubs.org/content/16/4/1438.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9552049 PubMed]<br />
<br />
==Gemcitabine & Vinorelbine {{#subobject:4dd538|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
<br />
===Regimen {{#subobject:b605f7|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.22609/full Dileo et al. 2007]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
====Chemotherapy====<br />
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 & 8<br />
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV over 10 minutes once per day on days 1 & 8<br />
<br />
'''21-day cycles'''<br />
<br />
===Reference===<br />
# Dileo P, Morgan JA, Zahrieh D, Desai J, Salesi JM, Harmon DC, Quigley MT, Polson K, Demetri GD, George S. Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial. Cancer. 2007 May 1;109(9):1863-9. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.22609/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17385194 PubMed]<br />
<br />
=Liposarcoma, all lines of therapy=<br />
''Note: this will be moved to a histology-specific page, shortly.''<br />
==Eribulin monotherapy {{#subobject:427859|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
===Regimen {{#subobject:2bcda0|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext Schöffski et al. 2016]<br />
| style="background-color:#1a9851" |Phase III<br />
|[[#Dacarbazine_monotherapy|Dacarbazine]]<br />
| style="background-color:#1a9850" |Superior OS (*)<br />
|-<br />
|}<br />
''Efficacy is based on the 2017 subgroup analysis.''<br />
====Chemotherapy====<br />
*[[Eribulin (Halaven)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8<br />
<br />
'''21-day cycles until progression'''<br />
<br />
===References===<br />
# Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, Grignani G, Camargo V, Bauer S, Rha SY, Blay JY, Hohenberger P, D'Adamo D, Guo M, Chmielowski B, Le Cesne A, Demetri GD, Patel SR. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016 Apr 16;387(10028):1629-37. Epub 2016 Feb 10. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01283-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26874885 PubMed]<br />
## '''Subgroup analysis:''' Demetri GD, Schöffski P, Grignani G, Blay JY, Maki RG, Van Tine BA, Alcindor T, Jones RL, D'Adamo DR, Guo M, Chawla S. Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol. 2017 Oct 20;35(30):3433-3439. Epub 2017 Aug 30. [http://ascopubs.org/doi/full/10.1200/JCO.2016.71.6605 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28854066 PubMed]<br />
<br />
=Rhabdomyosarcoma, all lines of therapy=<br />
''Note: this will be moved to a histology-specific page, shortly.''<br />
==VAC {{#subobject:4f2267|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VAC: '''<u>V</u>'''incristine, '''<u>A</u>'''ctinomycin D, '''<u>C</u>'''yclophosphamide<br />
===Regimen {{#subobject:060d90|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 Crist et al. 2001 (IRS-IV)]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[#VAI|VAI]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[[#VIE|VIE]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
To be completed<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]]<br />
*[[Dactinomycin (Cosmegen)]]<br />
*[[Cyclophosphamide (Cytoxan)]]<br />
<br />
===References===<br />
# Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091-102. [http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11408506 PubMed]<br />
<br />
==VAI {{#subobject:9ab538|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VAI: '''<u>V</u>'''incristine, '''<u>A</u>'''ctinomycin D, '''<u>I</u>'''fosfamide<br />
<br>IVA: '''<u>I</u>'''fosfamide, '''<u>V</u>'''incristine, '''<u>A</u>'''ctinomycin D<br />
===Regimen {{#subobject:49f6c6|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 Crist et al. 2001 (IRS-IV)]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[#VAC|VAC]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[[#VIE|VIE]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[http://ascopubs.org/doi/full/10.1200/JCO.2011.40.3287 Oberlin et al. 2012 (SIOP MMT95)]<br />
| style="background-color:#1a9851" |Phase III (C)<br />
|IVA/CEV/IVE<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
To be completed<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]]<br />
*[[Dactinomycin (Cosmegen)]]<br />
*[[Ifosfamide (Ifex)]]<br />
<br />
===References===<br />
# Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091-102. [http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11408506 PubMed]<br />
# Oberlin O, Rey A, Sanchez de Toledo J, Martelli H, Jenney ME, Scopinaro M, Bergeron C, Merks JH, Bouvet N, Ellershaw C, Kelsey A, Spooner D, Stevens MC. Randomized comparison of intensified six-drug versus standard three-drug chemotherapy for high-risk nonmetastatic rhabdomyosarcoma and other chemotherapy-sensitive childhood soft tissue sarcomas: long-term results from the International Society of Pediatric Oncology MMT95 study. J Clin Oncol. 2012 Jul 10;30(20):2457-65. Epub 2012 Jun 4. [http://ascopubs.org/doi/full/10.1200/JCO.2011.40.3287 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22665534 PubMed]<br />
<br />
==VI, then VDC/IE, then VAC, then VI {{#subobject:e080ff|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VI, then VDC/IE, then VAC, then VI: '''<u>V</u>'''incristine & '''<u>I</u>'''rinotecan, followed by '''<u>V</u>'''incristine, '''<u>D</u>'''oxorubicin, '''<u>C</u>'''yclophosphamide alternating with '''<u>I</u>'''fosfamide & '''<u>E</u>'''toposide, followed by '''<u>V</u>'''incristine, '''<u>A</u>'''ctinomycin D, '''<u>C</u>'''yclophosphamide, followed by '''<u>V</u>'''incristine & '''<u>I</u>'''rinotecan<br />
===Regimen {{#subobject:9a3f8d|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
|-<br />
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070550/ Weigel et al. 2015 (COG ARST0431)]<br />
| style="background-color:#91cf61" |Phase II<br />
|-<br />
|}<br />
''Note: this is a complicated 54-week regimen with no immediate plans to add it to HemOnc.org. Please refer to the original article.''<br />
===References===<br />
# Weigel BJ, Lyden E, Anderson JR, Meyer WH, Parham DM, Rodeberg DA, Michalski JM, Hawkins DS, Arndt CA. Intensive multiagent therapy, including dose-compressed cycles of ifosfamide/etoposide and vincristine/doxorubicin/cyclophosphamide, irinotecan, and radiation, in patients with high-risk rhabdomyosarcoma: A report from the Children's Oncology Group. J Clin Oncol. 2016 Jan 10;34(2):117-22. Epub 2015 Oct 26. [http://ascopubs.org/doi/full/10.1200/JCO.2015.63.4048 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070550/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26503200 PubMed]<br />
<br />
==VIE {{#subobject:1b4037|Regimen=1}}==<br />
{| class="wikitable" style="float:right; margin-left: 5px;"<br />
|-<br />
|[[#top|back to top]]<br />
|}<br />
VIE: '''<u>V</u>'''incristine, '''<u>I</u>'''fosfamide, '''<u>E</u>'''toposide<br />
===Regimen {{#subobject:f0d233|Variant=1}}===<br />
{| class="wikitable" style="width: 100%; text-align:center;" <br />
!Study<br />
![[Levels_of_Evidence#Evidence|Evidence]]<br />
!Comparator<br />
![[Levels_of_Evidence#Efficacy|Efficacy]]<br />
|-<br />
| rowspan="2" |[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 Crist et al. 2001 (IRS-IV)]<br />
| rowspan="2" style="background-color:#1a9851" |Phase III<br />
|[[#VAC|VAC]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|[[#VAI|VAI]]<br />
| style="background-color:#ffffbf" |Seems not superior<br />
|-<br />
|}<br />
To be completed<br />
====Chemotherapy====<br />
*[[Vincristine (Oncovin)]]<br />
*[[Ifosfamide (Ifex)]]<br />
*[[Etoposide (Vepesid)]]<br />
<br />
===References===<br />
# Crist WM, Anderson JR, Meza JL, Fryer C, Raney RB, Ruymann FB, Breneman J, Qualman SJ, Wiener E, Wharam M, Lobe T, Webber B, Maurer HM, Donaldson SS. Intergroup rhabdomyosarcoma study-IV: results for patients with nonmetastatic disease. J Clin Oncol. 2001 Jun 15;19(12):3091-102. [http://ascopubs.org/doi/full/10.1200/JCO.2001.19.12.3091 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11408506 PubMed]<br />
<br />
=Gastrointestinal stromal tumor (GIST), all lines of therapy=<br />
''Please see the [[Gastrointestinal stromal tumor|dedicated GIST page]].''<br />
<br />
[[Category:Soft tissue sarcoma regimens]]<br />
[[Category:Disease-specific pages]]<br />
[[Category:Soft tissue sarcomas]]</div>Waynelianghttps://hemonc.org/w/index.php?title=User:Wayneliang&diff=25925User:Wayneliang2018-03-29T21:18:59Z<p>Wayneliang: headshot re-add</p>
<hr />
<div>[[File:Liang.jpg|thumb|Wayne Liang, MD MS]]<br />
Wayne Liang, MD MS is a pediatric hematology/oncology attending physician at [https://www.childrensal.org/dr-wayne-liang-inf-dis-vir Children's of Alabama] and [https://providerdirectory.uabmedicine.org/provider/Wayne+Liang/573496 University of Alabama at Birmingham Medical Center], with a clinical focus in pediatric solid tumors. Dr. Liang is an [https://www.uab.edu/medicine/peds/hemonc-faculty/1673-wayne-h-liang-md-ms Assistant Professor of Pediatrics (Division of Hematology/Oncology)] and [https://www.uab.edu/medicine/informatics/faculty/faculty Informatics Institute] at [http://www.uab.edu/medicine/ University of Alabama at Birmingham School of Medicine]. Dr. Liang's research focuses on the integration and use of genomic information into electronic health records and clinical care workflows to support precision medicine care delivery. He participates as a clinical investigator for childhood cancer clinical trials through the [https://www.childrensoncologygroup.org/ Children's Oncology Group] and other cooperative groups. Dr. Liang is board-certified in Pediatrics and board-eligible in Pediatric Hematology/Oncology and Clinical Informatics. <br />
<br />
Wayne Liang, MD is the HemOnc.org Section Editor of [[:Category:Pediatric cancers|Pediatric Oncology]].<br />
<br />
==External Links==<br />
*[https://twitter.com/WayneLiangMD Twitter.com/WayneLiangMD]<br />
*[http://linkedin.com/in/wayneliang LinkedIn]<br />
*[http://www.wayneliangmd.com/ Doximity]</div>Waynelianghttps://hemonc.org/w/index.php?title=File:Liang.jpg&diff=25924File:Liang.jpg2018-03-29T20:10:19Z<p>Wayneliang: Wayneliang uploaded a new version of File:Liang.jpg</p>
<hr />
<div></div>Waynelianghttps://hemonc.org/w/index.php?title=User:Wayneliang&diff=25923User:Wayneliang2018-03-29T20:07:54Z<p>Wayneliang: Updated profile</p>
<hr />
<div>[[File:Liang.jpg|thumb|Wayne Liang, MD]]<br />
Wayne Liang, MD MS is a pediatric hematology/oncology attending physician at [https://www.childrensal.org/dr-wayne-liang-inf-dis-vir Children's of Alabama] and [https://providerdirectory.uabmedicine.org/provider/Wayne+Liang/573496 University of Alabama at Birmingham Medical Center], with a clinical focus in pediatric solid tumors. Dr. Liang is an [https://www.uab.edu/medicine/peds/hemonc-faculty/1673-wayne-h-liang-md-ms Assistant Professor of Pediatrics (Division of Hematology/Oncology)] and [https://www.uab.edu/medicine/informatics/faculty/faculty Informatics Institute] at [http://www.uab.edu/medicine/ University of Alabama at Birmingham School of Medicine]. Dr. Liang's research focuses on the integration and use of genomic information into electronic health records and clinical care workflows to support precision medicine care delivery. He participates as a clinical investigator for childhood cancer clinical trials through the [https://www.childrensoncologygroup.org/ Children's Oncology Group] and other cooperative groups. Dr. Liang is board-certified in Pediatrics and board-eligible in Pediatric Hematology/Oncology and Clinical Informatics. <br />
<br />
Wayne Liang, MD is the HemOnc.org Section Editor of [[:Category:Pediatric cancers|Pediatric Oncology]].<br />
<br />
==External Links==<br />
*[https://twitter.com/WayneLiangMD Twitter.com/WayneLiangMD]<br />
*[http://linkedin.com/in/wayneliang LinkedIn]<br />
*[http://www.wayneliangmd.com/ Doximity]</div>Waynelianghttps://hemonc.org/w/index.php?title=User:Wayneliang/Sandbox&diff=25921User:Wayneliang/Sandbox2018-03-29T19:16:19Z<p>Wayneliang: Created page with "test sandbox"</p>
<hr />
<div>test sandbox</div>Wayneliang