Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
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{{#lst:Section editor transclusions|aml}}
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{{#lst:Section editor transclusions|peds-sarcoma}}
 +
''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[Rhabdomyosarcoma_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
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|<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>
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|<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>
−
<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>
+
<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>
 
|}
 
|}
−
''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Acute promyelocytic leukemia - null regimens|this page]]. If you still can't find it, please let us know so we can add it.''
+
{{TOC limit|limit=4}}
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{{TOC limit|limit=3}}
+
=Intermediate Risk=
−
=Guidelines=
+
==COG ARST1431 Protocol A (VAC/VI Only)==
−
==ELN==
 
−
*'''2019:''' Sanz et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509567/ Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet]
 
−
===Older===
 
−
*'''2009:''' Sanz et al. [http://www.bloodjournal.org/content/113/9/1875.long Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet]
 
−
==[http://www.esmo.org/ ESMO]==
 
−
*'''2013:''' Fey et al. [http://annonc.oxfordjournals.org/content/24/suppl_6/vi138.full.pdf+html Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/23970018 PubMed]
 
−
==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf NCCN Guidelines - Acute Myeloid Leukemia]
 
−
=Upfront induction therapy=
 
−
==ADE & ATRA {{#subobject:e221d7|Regimen=1}}==
 
−
ADE & ATRA: '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''aunorubicin, '''<u>E</u>'''toposide, '''<u>A</u>'''ll-'''<u>T</u>'''rans '''<u>R</u>'''etinoic '''<u>A</u>'''cid
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:386fd2|Variant=1}}===
+
===Protocol, Cycles 1-4 (Weeks 1 through 12)===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/93/12/4131.long Burnett et al. 1999 (UK MRC AML12)]
 
−
|1993-1997
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#ADE_.26_ATRA|ADE & ATRA]], shorter duration
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2010.31.4310 Burnett et al. 2010 (UK MRC AML15)]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ATRA_.26_Idarubicin|"Spanish therapy"]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of RR/OS
 
−
|-
 
−
|}
 
−
''Note: this is included for historic purposes. Efficacy for UK MRC AML15 is based on the 2012 update, which was specifically pertinent to APL.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV once every 12 hours on days 1 to 10 (total dose: 2000 mg/m<sup>2</sup>)
+
*[[Vincristine (Oncovin)]] by the following BSA-based criteria:
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
+
**0.25-0.29 m<sup>2</sup> BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
+
**0.3-0.34 m<sup>2</sup> BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
====Targeted therapy====
+
**0.35-0.39 m<sup>2</sup> BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m<sup>2</sup>/day PO, starting on day 1 and continuing until remission or maximum of 60 days
+
**0.4-0.44 m<sup>2</sup> BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
'''One course'''
+
**0.45-0.49 m<sup>2</sup> BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
</div>
+
**0.5-0.54 m<sup>2</sup> BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
<div class="toccolours" style="background-color:#cbd5e7">
+
**0.55-0.59 m<sup>2</sup> BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
====Subsequent treatment====
+
**≥ 0.6 m<sup>2</sup> BSA: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
*UK MRC AML15: [[#ADE_.26_ATRA_88|ADE 8-3-5 + ATRA]] consolidation
+
*[[Dactinomycin (Cosmegen)]] by the following weight-based criteria:
−
</div></div>
+
**3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
−
===References===
+
**4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
−
# '''UK MRC AML12:''' Burnett AK, Grimwade D, Solomon E, Wheatley K, Goldstone AH. Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid: result of the randomized MRC trial. Blood. 1999 Jun 15;93(12):4131-43. [http://www.bloodjournal.org/content/93/12/4131.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/10361110 PubMed] NCT00002658
+
**6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
−
## '''Update:''' Burnett AK, Hills RK, Milligan DW, Goldstone AH, Prentice AG, McMullin MF, Duncombe A, Gibson B, Wheatley K. Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial. J Clin Oncol. 2010 Feb 1;28(4):586-95. Epub 2009 Dec 28. [https://doi.org/10.1200/JCO.2009.22.9088 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20038732 PubMed]
+
**7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
−
# '''UK MRC AML15:''' Burnett AK, Hills RK, Milligan D, Kjeldsen L, Kell J, Russell NH, Yin JA, Hunter A, Goldstone AH, Wheatley K. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011 Feb 1;29(4):369-77. Epub 2010 Dec 20. [https://doi.org/10.1200/JCO.2010.31.4310 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21172891 PubMed] ISRCTN17161961
+
**8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
−
## '''Update:''' Burnett AK, Hills RK, Grimwade D, Jovanovic JV, Craig J, McMullin MF, Kell J, Wheatley K, Yin JA, Hunter A, Milligan D, Russell NH; United Kingdom National Cancer Research Institute Acute Myeloid Leukaemia Subgroup. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial. Leukemia. 2013 Apr;27(4):843-51. Epub 2012 Dec 10. [https://www.nature.com/articles/leu2012360 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23222369 PubMed]
+
**10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
−
## '''Update:''' Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the MRC AML15 trial. J Clin Oncol. 2013 Sep 20;31(27):3360-8. Epub 2013 Aug 12. [https://doi.org/10.1200/jco.2012.47.4874 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23940227 PubMed]
+
**11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
−
==Arsenic trioxide monotherapy {{#subobject:bdedf2|Regimen=1}}==
+
**12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
−
<div class="toccolours" style="background-color:#eeeeee">
+
**≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
−
===Regimen variant #1, 0.15 mg/kg (pediatric dosing) {{#subobject:359bzc|Variant=1}}===
+
*[[Cyclophosphamide (Cytoxan)]] by the following BSA-based criteria:
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
+
**0.25-0.29 m<sup>2</sup> BSA: 220 mg IV over 60 minutes on day 1 of weeks 1 and 7
−
!style="width: 33%"|Study
+
**0.3-0.34 m<sup>2</sup> BSA: 280 mg IV over 60 minutes on day 1 of weeks 1 and 7
−
!style="width: 33%"|Years of enrollment
+
**0.35-0.39 m<sup>2</sup> BSA: 360 mg IV over 60 minutes on day 1 of weeks 1 and 7
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**0.4-0.44 m<sup>2</sup> BSA: 440 mg IV over 60 minutes on day 1 of weeks 1 and 7
−
|-
+
**0.45-0.49 m<sup>2</sup> BSA: 520 mg IV over 60 minutes on day 1 of weeks 1 and 7
−
|[https://doi.org/10.1182/blood-2005-08-3532 Mathews et al. 2006]
+
**0.5-0.54 m<sup>2</sup> BSA: 600 mg IV over 60 minutes on day 1 of weeks 1 and 7
−
|1998-2004
+
**0.55-0.59 m<sup>2</sup> BSA: 660 mg IV over 60 minutes on day 1 of weeks 1 and 7
−
| style="background-color:#91cf61" |Non-randomized
+
**≥ 0.6 m<sup>2</sup> BSA: 1200 mg/m<sup>2</sup> IV over 60 minutes on day 1 of weeks 1 and 7
−
|-
+
*[[Irinotecan (Camptosar)]] by the following BSA-based criteria:
−
|}
+
**0.25-0.29 m<sup>2</sup> BSA: 8 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
−
''Note: the maximum duration was decreased from 75 to 60 days after 2001.''
+
**0.3-0.34 m<sup>2</sup> BSA: 12 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
−
<div class="toccolours" style="background-color:#b3e2cd">
+
**0.35-0.39 m<sup>2</sup> BSA: 15 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
−
====Targeted therapy====
+
**0.4-0.44 m<sup>2</sup> BSA: 18 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV over 2 to 3 hours once per day  
+
**0.45-0.49 m<sup>2</sup> BSA: 22 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
−
'''Continued until CR or up to 60 days'''
+
**0.5-0.54 m<sup>2</sup> BSA: 24 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
−
</div>
+
**0.55-0.59 m<sup>2</sup> BSA: 28 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
−
<div class="toccolours" style="background-color:#cbd5e7">
+
**≥ 0.6 m<sup>2</sup> BSA: 50 mg/m<sup>2</sup> IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
−
====Subsequent treatment====
+
====Supportive Medications====
−
*Patients in CR: [[#Arsenic_trioxide_monotherapy_2|Arsenic trioxide]] consolidation
+
*[[Mesna (Mesnex)]] by the following BSA-based criteria:
−
</div></div><br>
+
**0.25-0.29 m<sup>2</sup> BSA: 176 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
<div class="toccolours" style="background-color:#eeeeee">
+
**0.3-0.34 m<sup>2</sup> BSA: 224 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
===Regimen variant #2, 0.16 mg/kg {{#subobject:31ae8c|Variant=1}}===
+
**0.35-0.39 m<sup>2</sup> BSA: 288 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
+
**0.4-0.44 m<sup>2</sup> BSA: 352 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
!style="width: 20%"|Study
+
**0.45-0.49 m<sup>2</sup> BSA: 416 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
!style="width: 20%"|Years of enrollment
+
**0.5-0.54 m<sup>2</sup> BSA: 480 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**0.55-0.59 m<sup>2</sup> BSA: 528 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
!style="width: 20%"|Comparator
+
**≥ 0.6 m<sup>2</sup> BSA: 960 mg/m<sup>2</sup> IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
***[[Mesna (Mesnex)]] can also be given PO at twice the IV dose
−
|-
 
−
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC397380/ Shen et al. 2004]
 
−
|rowspan=2|2001-2003
 
−
| rowspan="2" style="background-color:#1a9851" |Randomized (C)
 
−
|1. [[#Arsenic_trioxide_.26_ATRA|Arsenic trioxide & ATRA]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
−
|-
 
−
|2. [[#ATRA_monotherapy|ATRA]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] 0.16 mg/kg IV once per day
 
−
'''Continued until CR'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients in CR: Consolidation, see text for details
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 10 mg (flat dose) {{#subobject:35af8c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1182/blood-2005-08-3532 Mathews et al. 2006]
 
−
|1998-2004
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
''Note: the maximum duration was decreased from 75 to 60 days after 2001.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] 10 mg IV over 2 to 3 hours once per day
 
−
'''Continued until CR or up to 60 days'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients in CR: [[#Arsenic_trioxide_monotherapy_2|Arsenic trioxide]] consolidation
 
−
</div></div>
 
−
===References===
 
−
# Shen ZX, Shi ZZ, Fang J, Gu BW, Li JM, Zhu YM, Shi JY, Zheng PZ, Yan H, Liu YF, Chen Y, Shen Y, Wu W, Tang W, Waxman S, De Thé H, Wang ZY, Chen SJ, Chen Z. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5328-35. Epub 2004 Mar 24. [http://www.pnas.org/content/101/15/5328.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC397380/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15044693 PubMed]
 
−
# Mathews V, George B, Lakshmi KM, Viswabandya A, Bajel A, Balasubramanian P, Shaji RV, Srivastava VM, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006 Apr 1;107(7):2627-32. Epub 2005 Dec 13. [https://doi.org/10.1182/blood-2005-08-3532 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16352810 PubMed]
 
−
## '''Update:''' Mathews V, George B, Chendamarai E, Lakshmi KM, Desire S, Balasubramanian P, Viswabandya A, Thirugnanam R, Abraham A, Shaji RV, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol. 2010 Aug 20;28(24):3866-71. Epub 2010 Jul 19. [https://doi.org/10.1200/jco.2010.28.5031 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20644086 PubMed]
 
−
==Arsenic trioxide & ATRA {{#subobject:2b304d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 0.15/45 {{#subobject:a85b5f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/107/9/3469.long Estey et al. 2005]
 
−
|2002-2005
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881307/ Ravandi et al. 2008]
 
−
|2002-2007
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1300874 Lo-Coco et al. 2013 (GIMEMA/DSIL APL0406)]
 
−
|2007-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 
−
|[[#ATRA_.26_Idarubicin|ATRA & Idarubicin]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> <br>(HR 0.15, 95% CI 0.03-0.67)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for GIMEMA/DSIL APL0406 is based on the 2019 update.''<br>
 
−
''Note: In Estey et al. 2005, arsenic trioxide was started on day 11, but was later modified to start on day 1 after a death due to hyperleukocytosis and intracranial hemorrhage during induction. GIMEMA/DSIL APL0406: Patients with <u>low-</u> or <u>intermediate-risk</u> APL (white blood cell count at presentation less than or equal to 10 x 10<sup>9</sup>/L) were eligible.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV over 2 hours once per day, starting on day 1 and continuing until hematologic complete remission or maximum of 60 days.
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day, starting on day 1 and continuing until hematologic complete remission or maximum of 60 days (GIMEMA/DSIL APL0406) or 90 days (Estey et al. 2005 & Ravandi et al. 2008).
 
−
====Supportive therapy====
 
−
*''As described in GIMEMA/DSIL APL0406:''
 
−
*[[Prednisone (Sterapred)]] 0.5 mg/kg PO once per day from days 1 until the end of induction or the onset of differentiation syndrome
 
−
**Patients who develop differentiation syndrome then received: [[Dexamethasone (Decadron)]] 10 mg IV every 12 hours until signs and symptoms resolve, and for a minimum of 3 days
 
−
*Hemostatic support: Transfusions to keep platelet count greater than 30 x 10<sup>9</sup>/L for the first 10 days of induction and greater than 20 x 10<sup>9</sup>/L for the remainder of induction
 
−
*[[Hydroxyurea (Hydrea)]] by the following criteria:
 
−
**Patients with WBC count greater than 10 x 10<sup>9</sup>/L and less than 50 x 10<sup>9</sup>/L after the start of therapy: 500 mg PO four times per day, given until WBC count is less than 10 x 10<sup>9</sup>/L
 
−
**Patients with WBC count greater than 50 x 10<sup>9</sup>/L after the start of therapy: 1000 mg PO four times per day, given until WBC count is less than 10 x 10<sup>9</sup>/L
 
−
'''Up to 60- to 90-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Arsenic_trioxide_.26_ATRA_2|Arsenic trioxide & ATRA]] consolidation
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 0.16/25 {{#subobject:9c8a05|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC397380/ Shen et al. 2004]
 
−
|2001-2003
 
−
| style="background-color:#1a9851" |Randomized (E-esc)
 
−
|1. [[#Arsenic_trioxide_monotherapy|Arsenic trioxide]]<br>2. [[#ATRA_monotherapy|ATRA]]
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2013.48.8312 Zhu et al. 2013]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#Realgar-Indigo_naturalis_formula_monotherapy|Realgar-Indigo naturalis formula]]
 
−
| style="background-color:#eeee01" |Non-inferior DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] 0.16 mg/kg IV once per day, starting day 1 and continuing until remission
 
−
*[[All-trans retinoic acid (ATRA)]] 12.5 mg/m<sup>2</sup> PO twice per day, starting day 1 and continuing until remission or maximum of 90 days.
 
−
'''Up to 90-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients achieving CR: chemotherapy-based consolidation and maintenance. These details are available in the original paper but are omitted here.
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 0.3/45 {{#subobject:e391b9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00193-X Burnett et al. 2015 (UK NCRI AML17)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[#ATRA_.26_Idarubicin|ATRA & Idarubicin]]
 
−
|
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of QoL
 
−
|-
 
−
|}
 
−
''Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] 0.3 mg/kg IV once per day on days 1 to 5, then 0.25 mg/kg IV twice per week on weeks 2 to 8
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day, starting on day 1 and continuing until hematologic complete remission or maximum of 60 days
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Arsenic_trioxide_.26_ATRA_2|Arsenic trioxide & ATRA]] consolidation
 
−
</div></div>
 
−
===References===
 
−
# Shen ZX, Shi ZZ, Fang J, Gu BW, Li JM, Zhu YM, Shi JY, Zheng PZ, Yan H, Liu YF, Chen Y, Shen Y, Wu W, Tang W, Waxman S, De Thé H, Wang ZY, Chen SJ, Chen Z. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5328-35. Epub 2004 Mar 24. [http://www.pnas.org/content/101/15/5328.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC397380/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/15044693 PubMed]
 
−
## '''Update:''' Hu J, Liu YF, Wu CF, Xu F, Shen ZX, Zhu YM, Li JM, Tang W, Zhao WL, Wu W, Sun HP, Chen QS, Chen B, Zhou GB, Zelent A, Waxman S, Wang ZY, Chen SJ, Chen Z. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3342-7. Epub 2009 Feb 18. [http://www.pnas.org/content/106/9/3342.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651325/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19225113 PubMed] content property of [http://hemonc.org HemOnc.org]
 
−
# Estey E, Garcia-Manero G, Ferrajoli A, Faderl S, Verstovsek S, Jones D, Kantarjian H. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006 May 1;107(9):3469-73. Epub 2005 Dec 22. [http://www.bloodjournal.org/content/107/9/3469.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16373661 PubMed]
 
−
# Ravandi F, Estey E, Jones D, Faderl S, O'Brien S, Fiorentino J, Pierce S, Blamble D, Estrov Z, Wierda W, Ferrajoli A, Verstovsek S, Garcia-Manero G, Cortes J, Kantarjian H. Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol. 2009 Feb 1;27(4):504-10. Epub 2008 Dec 15. [https://doi.org/10.1200/jco.2008.18.6130 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881307/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19075265 PubMed]
 
−
## '''Update:''' Abaza Y, Kantarjian H, Garcia-Manero G, Estey E, Borthakur G, Jabbour E, Faderl S, O'Brien S, Wierda W, Pierce S, Brandt M, McCue D, Luthra R, Patel K, Kornblau S, Kadia T, Daver N, DiNardo C, Jain N, Verstovsek S, Ferrajoli A, Andreeff M, Konopleva M, Estrov Z, Foudray M, McCue D, Cortes J, Ravandi F. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood. 2017 Mar 9;129(10):1275-1283. [http://www.bloodjournal.org/content/129/10/1275 link to full article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5413297/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28003274 PubMed]
 
−
# '''GIMEMA/DSIL APL0406:''' Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. [https://doi.org/10.1056/NEJMoa1300874 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23841729 PubMed] NCT00482833
 
−
## '''HRQoL analysis:''' Efficace F, Mandelli F, Avvisati G, Cottone F, Ferrara F, Di Bona E, Specchia G, Breccia M, Levis A, Sica S, Finizio O, Kropp MG, Fioritoni G, Cerqui E, Vignetti M, Amadori S, Schlenk RF, Platzbecker U, Lo-Coco F. Randomized phase III trial of retinoic acid and arsenic trioxide versus retinoic acid and chemotherapy in patients with acute promyelocytic leukemia: health-related quality-of-life outcomes. J Clin Oncol. 2014 Oct 20;32(30):3406-12. Epub 2014 Sep 22. [https://doi.org/10.1200/JCO.2014.55.3453 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25245446 PubMed]
 
−
## '''Update:''' Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute promyelocytic leukemia: final results of the randomized Italian-German APL0406 trial. J Clin Oncol. 2017 Feb 20;35(6):605-612. Epub 2016 Oct 31. [https://doi.org/10.1200/JCO.2016.67.1982 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27400939  PubMed]
 
−
## '''Update:''' Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts CH, Hanel M, Rollig C, Schmitz N, Link H, Frairia C, Fozza C, Maria D'Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Voso MT, Ehninger G, Schlenk RF, Lo-Coco F. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial. Leukemia. 2020 Mar;34(3):914-918. Epub 2019 Oct 14. [https://doi.org/10.1038/s41375-019-0589-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31611624 PubMed]
 
−
# Zhu HH, Wu DP, Jin J, Li JY, Ma J, Wang JX, Jiang H, Chen SJ, Huang XJ. Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial. J Clin Oncol. 2013 Nov 20;31(33):4215-21. Epub 2013 Oct 14. [https://doi.org/10.1200/JCO.2013.48.8312 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24127444 PubMed] ChiCTR-TRC-12002151
 
−
# '''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Bowen D, Kell J, Knapper S, Morgan YG, Lok J, Grech A, Jones G, Khwaja A, Friis L, McMullin MF, Hunter A, Clark RE, Grimwade D; UK National Cancer Research Institute Acute Myeloid Leukaemia Working Group. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Oct;16(13):1295-305. Epub 2015 Sep 14. [https://doi.org/10.1016/S1470-2045(15)00193-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26384238 PubMed] ISRCTN55675535
 
−
## '''Update:''' Russell N, Burnett A, Hills R, Betteridge S, Dennis M, Jovanovic J, Dillon R, Grimwade D; NCRI AML Working Group. Attenuated arsenic trioxide plus ATRA therapy for newly diagnosed and relapsed APL: long-term follow-up of the AML17 trial. Blood. 2018 Sep 27;132(13):1452-1454. Epub 2018 Aug 10. [https://doi.org/10.1182/blood-2018-05-851824 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6225356/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30097508 PubMed]
 
−
== Arsenic trioxide, ATRA, Gemtuzumab ozogamicin {{#subobject:533ccc|Regimen=1}} ==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, GO 6 mg/m<sup>2</sup> {{#subobject:d00673|Variant=2}}===
+
===Protocol, Cycles 5-10 (Weeks 13 through 30)===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00193-X Burnett et al. 2015 (UK NCRI AML17)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#ATRA_.26_Idarubicin|ATRA & Idarubicin]]
 
−
|
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of QoL
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] 0.3 mg/kg IV once per day on days 1 to 5, then 0.25 mg/kg IV twice per week on weeks 2 to 8
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day, starting on day 1 and continuing until hematologic complete remission or maximum of 60 days
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] by the following criteria:
 
−
**WBC count greater than 10 x 10<sup>9</sup>/L: 6 mg/m<sup>2</sup> IV once on day 1
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Arsenic_trioxide_.26_ATRA_2|Arsenic trioxide & ATRA]] consolidation
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, GO 9 mg/m<sup>2</sup> {{#subobject:7f2ac1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/107/9/3469.long Estey et al. 2005]
 
−
|2002-2005
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881307/ Ravandi et al. 2008]
 
−
|2002-2007
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: in some protocols, if GO was unavailable, Idarubicin 12mg/m<sup>2</sup> given instead. The original protocol was modified between Estey et al. 2005 and Ravandi et al. 2008. Estey et al. 2005 covered part of the whole cohort. In the initial protocol, arsenic trioxide was started on day 11, and gemtuzumab ozogamicin was only used for high risk patients. After a death due to hyperleukocytosis and intracranial hemorrhage during induction, the protocol was modified as described in Ravandi et al. 2008 so arsenic trioxide was started on day 1, and gemtuzumab ozogamicin was given if WBC count went greater than 30 x 10<sup>9</sup>/L for any patient in the first four weeks of therapy.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV over 2 hours once per day on days 1 to 28, or until CR
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 28, or until CR
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Gemtuzumab ozogamicin (Mylotarg)]] by the following criteria:
 
−
**WBC count greater than 10 x 10<sup>9</sup>/L: 9 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*"Prophylactic and therapeutic antibiotics and transfusion of blood products to maintain platelet counts more than 30 x 10<sup>9</sup>/L, fibrinogen more than 150 mg/dL, and the international normalized ratio for prothrombin time less than 1.5" per institutional guidelines
 
−
*[[Unfractionated heparin (UFH)]] or [[Tranexamic acid (Cyklokapron)]] used if clinically indicated
 
−
*[[Methylprednisolone (Solumedrol)]] by the following study-specific criteria:
 
−
**Estey et al. 2005: 20 mg PO once per day for 10 days to decrease risk of differentiation syndrome
 
−
**Ravandi et al. 2008: 50 mg PO once per day for 5 days to decrease risk of differentiation syndrome
 
−
'''28-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Arsenic_trioxide_.26_ATRA_2|Arsenic trioxide & ATRA]] consolidation
 
−
</div></div>
 
−
===References===
 
−
# Estey E, Garcia-Manero G, Ferrajoli A, Faderl S, Verstovsek S, Jones D, Kantarjian H. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006 May 1;107(9):3469-73. Epub 2005 Dec 22. [http://www.bloodjournal.org/content/107/9/3469.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16373661 PubMed]
 
−
## '''Update:''' Abaza Y, Kantarjian H, Garcia-Manero G, Estey E, Borthakur G, Jabbour E, Faderl S, O'Brien S, Wierda W, Pierce S, Brandt M, McCue D, Luthra R, Patel K, Kornblau S, Kadia T, Daver N, DiNardo C, Jain N, Verstovsek S, Ferrajoli A, Andreeff M, Konopleva M, Estrov Z, Foudray M, McCue D, Cortes J, Ravandi F. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood. 2017 Mar 9;129(10):1275-1283. [http://www.bloodjournal.org/content/129/10/1275 link to full article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5413297/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28003274 PubMed]
 
−
# Ravandi F, Estey E, Jones D, Faderl S, O'Brien S, Fiorentino J, Pierce S, Blamble D, Estrov Z, Wierda W, Ferrajoli A, Verstovsek S, Garcia-Manero G, Cortes J, Kantarjian H. Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J Clin Oncol. 2009 Feb 1;27(4):504-10. Epub 2008 Dec 15. [https://doi.org/10.1200/jco.2008.18.6130 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881307/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19075265 PubMed]
 
−
## '''Update:''' Abaza Y, Kantarjian H, Garcia-Manero G, Estey E, Borthakur G, Jabbour E, Faderl S, O'Brien S, Wierda W, Pierce S, Brandt M, McCue D, Luthra R, Patel K, Kornblau S, Kadia T, Daver N, DiNardo C, Jain N, Verstovsek S, Ferrajoli A, Andreeff M, Konopleva M, Estrov Z, Foudray M, McCue D, Cortes J, Ravandi F. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood. 2017 Mar 9;129(10):1275-1283. [http://www.bloodjournal.org/content/129/10/1275 link to full article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5413297/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28003274 PubMed]
 
−
# '''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Bowen D, Kell J, Knapper S, Morgan YG, Lok J, Grech A, Jones G, Khwaja A, Friis L, McMullin MF, Hunter A, Clark RE, Grimwade D; UK National Cancer Research Institute Acute Myeloid Leukaemia Working Group. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Oct;16(13):1295-305. Epub 2015 Sep 14. [https://doi.org/10.1016/S1470-2045(15)00193-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/26384238 PubMed] ISRCTN55675535
 
−
## '''Update:''' Russell N, Burnett A, Hills R, Betteridge S, Dennis M, Jovanovic J, Dillon R, Grimwade D; NCRI AML Working Group. Attenuated arsenic trioxide plus ATRA therapy for newly diagnosed and relapsed APL: long-term follow-up of the AML17 trial. Blood. 2018 Sep 27;132(13):1452-1454. Epub 2018 Aug 10. [https://doi.org/10.1182/blood-2018-05-851824 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6225356/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30097508 PubMed]
 
−
 
 
−
==Arsenic trioxide, ATRA, Idarubicin {{#subobject:e30b39|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:50c777|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1182/blood-2012-02-410746 Iland et al. 2012 (ALLG APML4)]
 
−
|2004-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV over 2 hours once per day on days 9 to 36
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 36
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Idarubicin (Idamycin)]] by the following criteria:
+
*[[Vincristine (Oncovin)]] by the following BSA-based criteria:
−
**Patients up to age 61: 12 mg/m<sup>2</sup> IV once per day on days 2, 4, 6, 8
+
**0.25-0.29 m<sup>2</sup> BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
**Patients 61 to 70 years old: 9 mg/m<sup>2</sup> IV once per day on days 2, 4, 6, 8
+
**0.3-0.34 m<sup>2</sup> BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
**Patients older than 70: 6 mg/m<sup>2</sup> IV once per day on days 2, 4, 6, 8
+
**0.35-0.39 m<sup>2</sup> BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
====Supportive therapy====
+
**0.4-0.44 m<sup>2</sup> BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
*[[Prednisone (Sterapred)]] 1 mg/kg PO once per day on days 1 to 10, or until WBC count falls below 1 x 10<sup>9</sup>/L, or until resolution of differentiation syndrome (whichever occurs last)
+
**0.45-0.49 m<sup>2</sup> BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
*Hemostatic support : Values checked and products transfused once or twice per day to keep platelet count greater than 30 x 10<sup>9</sup>/L, fibrinogen greater than 1.5 g/L (150 mg/dL), normal PT and PTT
+
**0.5-0.54 m<sup>2</sup> BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
*Electrolyte support while on [[Arsenic trioxide (Trisenox)]]: supplemental potassium and magnesium given to keep levels in the upper half of their normal ranges
+
**0.55-0.59 m<sup>2</sup> BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
'''36-day course'''
+
**≥ 0.6 m<sup>2</sup> BSA: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
</div>
+
*[[Dactinomycin (Cosmegen)]] by the following weight-based criteria:
−
<div class="toccolours" style="background-color:#cbd5e7">
+
**3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
====Subsequent treatment====
+
**4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
*[[#Arsenic_trioxide_.26_ATRA_2|Arsenic trioxide & ATRA]] consolidation, in 3 to 4 weeks
+
**6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
</div></div>
+
**7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
===References===
+
**8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
# '''ALLG APML4:''' Iland HJ, Bradstock K, Supple SG, Catalano A, Collins M, Hertzberg M, Browett P, Grigg A, Firkin F, Hugman A, Reynolds J, Di Iulio J, Tiley C, Taylor K, Filshie R, Seldon M, Taper J, Szer J, Moore J, Bashford J, Seymour JF; Australasian Leukaemia and Lymphoma Group. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood. 2012 Aug 23;120(8):1570-80. Epub 2012 Jun 19. [https://doi.org/10.1182/blood-2012-02-410746 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22715121 PubMed] ACTRN12605000070639
+
**10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
==ATRA monotherapy {{#subobject:45c33c|Regimen=1}}==
+
**11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
 +
**12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
 +
**≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
 +
*[[Cyclophosphamide (Cytoxan)]] by the following BSA-based criteria:
 +
**0.25-0.29 m<sup>2</sup> BSA: 220 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
 +
**0.3-0.34 m<sup>2</sup> BSA: 280 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
 +
**0.35-0.39 m<sup>2</sup> BSA: 360 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
 +
**0.4-0.44 m<sup>2</sup> BSA: 440 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
 +
**0.45-0.49 m<sup>2</sup> BSA: 520 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
 +
**0.5-0.54 m<sup>2</sup> BSA: 600 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
 +
**0.55-0.59 m<sup>2</sup> BSA: 660 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
 +
**≥ 0.6 m<sup>2</sup> BSA: 1200 mg/m<sup>2</sup> IV over 60 minutes on day 1 of weeks 13, 22, 28
 +
*[[Irinotecan (Camptosar)]] by the following BSA-based criteria:
 +
**0.25-0.29 m<sup>2</sup> BSA: 8 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
 +
**0.3-0.34 m<sup>2</sup> BSA: 12 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
 +
**0.35-0.39 m<sup>2</sup> BSA: 15 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
 +
**0.4-0.44 m<sup>2</sup> BSA: 18 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
 +
**0.45-0.49 m<sup>2</sup> BSA: 22 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
 +
**0.5-0.54 m<sup>2</sup> BSA: 24 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
 +
**0.55-0.59 m<sup>2</sup> BSA: 28 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
 +
**≥ 0.6 m<sup>2</sup> BSA: 50 mg/m<sup>2</sup> IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
 +
====Supportive Medications====
 +
*[[Mesna (Mesnex)]] by the following BSA-based criteria:
 +
**0.25-0.29 m<sup>2</sup> BSA: 176 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.3-0.34 m<sup>2</sup> BSA: 224 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.35-0.39 m<sup>2</sup> BSA: 288 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.4-0.44 m<sup>2</sup> BSA: 352 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.45-0.49 m<sup>2</sup> BSA: 416 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.5-0.54 m<sup>2</sup> BSA: 480 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.55-0.59 m<sup>2</sup> BSA: 528 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**≥ 0.6 m<sup>2</sup> BSA: 960 mg/m<sup>2</sup> IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
***[[Mesna (Mesnex)]] can also be given PO at twice the IV dose
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:430573|Variant=1}}===
+
===Protocol, Cycles 11-14 (Weeks 31 through 42)===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199105163242002 Warrell et al. 1991]
 
−
|NR
 
−
| style="background-color:#ffffbe" |Pilot, <20 pts
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/82/11/3241.long Fenaux et al. 1993 (EAPLG APL 91)]
 
−
|1991-1992
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|7+3d
 
−
| style="background-color:#1a9850" |Superior EFS
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199710093371501 Tallman et al. 1997 (ECOG E2491)]
 
−
|1992-1995
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|Cytarabine & Daunorubicin
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
''Note: These obsolete regimens are here for historical reference; ATRA is no longer used as monotherapy for induction; some patients in EAPLG APL 91 received concurrent chemotherapy (see paper for details)''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day, starting day 1 and continuing until remission or maximum of 90 days
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*EAPLG APL 91: [[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin]] consolidation
 
−
*ECOG E2491: ATRA consolidation, then [[#Cytarabine_.26_Daunorubicin|cytarabine & daunorubicin]] consolidation
 
−
</div></div>
 
−
===References===
 
−
# Warrell RP Jr, Frankel SR, Miller WH Jr, Scheinberg DA, Itri LM, Hittelman WN, Vyas R, Andreeff M, Tafuri A, Jakubowski A, Gabrilove J, Gordon MS, Dmitrovsky E. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med. 1991 May 16;324(20):1385-93. [https://doi.org/10.1056/NEJM199105163242002 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1850498 PubMed]
 
−
# '''EAPLG APL 91:''' Fenaux P, Le Deley MC, Castaigne S, Archimbaud E, Chomienne C, Link H, Guerci A, Duarte M, Daniel MT, Bowen D, Huebner G, Bauters F, Fegueux N, Fey M, Sanz M, Lowenberg B, Maloisel F, Auzanneau G, Sadoun A, Gardin C, Bastion Y, Ganser A, Jacky E, Dombret H, Chastang C, Degos L; European APL Group. Effect of all transretinoic acid in newly diagnosed acute promyelocytic leukemia: results of a multicenter randomized trial. Blood. 1993 Dec 1;82(11):3241-9. [http://www.bloodjournal.org/content/82/11/3241.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8241496 PubMed]
 
−
## '''Update:''' Fenaux P, Chevret S, Guerci A, Fegueux N, Dombret H, Thomas X, Sanz M, Link H, Maloisel F, Gardin C, Bordessoule D, Stoppa AM, Sadoun A, Muus P, Wandt H, Mineur P, Whittaker JA, Fey M, Daniel MT, Castaigne S, Degos L; European APL Group. Long-term follow-up confirms the benefit of all-trans retinoic acid in acute promyelocytic leukemia. Leukemia. 2000 Aug;14(8):1371-7. [https://doi.org/10.1038/sj.leu.2401859 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10942231 PubMed]
 
−
<!-- Presented in part at the 36th meeting of the American Society of Hematology, Seattle, December 1–5, 1995. -->
 
−
# '''ECOG E2491:''' Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, Shepherd L, Willman C, Bloomfield CD, Rowe JM, Wiernik PH. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997 Oct 9;337(15):1021-8. Erratum in: N Engl J Med 1997 Nov 27;337(22):1639. [https://doi.org/10.1056/NEJM199710093371501 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9321529 PubMed]
 
−
## '''Update:''' Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Woods WG, Ogden A, Weinstein H, Shepherd L, Willman C, Bloomfield CD, Rowe JM, Wiernik PH. All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol. Blood. 2002 Dec 15;100(13):4298-302. Epub 2002 Aug 15. [http://www.bloodjournal.org/content/100/13/4298.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/12393590 PubMed]
 
−
 
 
−
==ATRA, Cytarabine, Daunorubicin {{#subobject:dade93|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 45/1400/180 {{#subobject:c7080e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.08.1596 Adès et al. 2006 (EAPLG APL 2000)]
 
−
|2000-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ATRA_.26_Daunorubicin|ATRA & Daunorubicin]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
''Note: This induction arm was a randomization for young (less than 60), low-risk (WBC count less than 10 x 10<sup>9</sup>/L) patients. High-risk (WBC count greater than 10 x 10<sup>9</sup>/L) patients received this regimen in a non-randomized fashion, along with intrathecal therapy during consolidation.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day, starting day 1 and continuing until remission or maximum of 90 days
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 3 (total dose: 1400 mg/m<sup>2</sup>)
+
*[[Vincristine (Oncovin)]] by the following BSA-based criteria:
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 3 to 5
+
**0.25-0.29 m<sup>2</sup> BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
'''One course of up to 90 days'''
+
**0.3-0.34 m<sup>2</sup> BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
</div>
+
**0.35-0.39 m<sup>2</sup> BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
<div class="toccolours" style="background-color:#cbd5e7">
+
**0.4-0.44 m<sup>2</sup> BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
====Subsequent treatment====
+
**0.45-0.49 m<sup>2</sup> BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
*[[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin]] consolidation
+
**0.5-0.54 m<sup>2</sup> BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
</div></div><br>
+
**0.55-0.59 m<sup>2</sup> BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
 +
**≥ 0.6 m<sup>2</sup> BSA: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
 +
*[[Dactinomycin (Cosmegen)]] by the following weight-based criteria:
 +
**3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
 +
**4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
 +
**6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
 +
**7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
 +
**8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
 +
**10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
 +
**11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
 +
**12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
 +
**≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
 +
*[[Cyclophosphamide (Cytoxan)]] by the following BSA-based criteria:
 +
**0.25-0.29 m<sup>2</sup> BSA: 220 mg IV over 60 minutes on day 1 of weeks 34, 40
 +
**0.3-0.34 m<sup>2</sup> BSA: 280 mg IV over 60 minutes on day 1 of weeks 34, 40
 +
**0.35-0.39 m<sup>2</sup> BSA: 360 mg IV over 60 minutes on day 1 of weeks 34, 40
 +
**0.4-0.44 m<sup>2</sup> BSA: 440 mg IV over 60 minutes on day 1 of weeks 34, 40
 +
**0.45-0.49 m<sup>2</sup> BSA: 520 mg IV over 60 minutes on day 1 of weeks 34, 40
 +
**0.5-0.54 m<sup>2</sup> BSA: 600 mg IV over 60 minutes on day 1 of weeks 34, 40
 +
**0.55-0.59 m<sup>2</sup> BSA: 660 mg IV over 60 minutes on day 1 of weeks 34, 40
 +
**≥ 0.6 m<sup>2</sup> BSA: 1200 mg/m<sup>2</sup> IV over 60 minutes on day 1 of weeks 34, 40
 +
*[[Irinotecan (Camptosar)]] by the following BSA-based criteria:
 +
**0.25-0.29 m<sup>2</sup> BSA: 8 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
 +
**0.3-0.34 m<sup>2</sup> BSA: 12 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
 +
**0.35-0.39 m<sup>2</sup> BSA: 15 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
 +
**0.4-0.44 m<sup>2</sup> BSA: 18 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
 +
**0.45-0.49 m<sup>2</sup> BSA: 22 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
 +
**0.5-0.54 m<sup>2</sup> BSA: 24 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
 +
**0.55-0.59 m<sup>2</sup> BSA: 28 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
 +
**≥ 0.6 m<sup>2</sup> BSA: 50 mg/m<sup>2</sup> IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
 +
====Supportive Medications====
 +
*[[Mesna (Mesnex)]] by the following BSA-based criteria:
 +
**0.25-0.29 m<sup>2</sup> BSA: 176 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.3-0.34 m<sup>2</sup> BSA: 224 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.35-0.39 m<sup>2</sup> BSA: 288 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.4-0.44 m<sup>2</sup> BSA: 352 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.45-0.49 m<sup>2</sup> BSA: 416 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.5-0.54 m<sup>2</sup> BSA: 480 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.55-0.59 m<sup>2</sup> BSA: 528 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**≥ 0.6 m<sup>2</sup> BSA: 960 mg/m<sup>2</sup> IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
***[[Mesna (Mesnex)]] can also be given PO at twice the IV dose
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, 45/1400/200 {{#subobject:8ee9d6|Variant=1}}===
+
===Protocol, Maintenance Cycles 1-6===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ Powell et al. 2010 (C9710)]
 
−
|1999-2004
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day, starting day 1 and continuing until remission or maximum of 90 days
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 3 (total dose: 1400 mg/m<sup>2</sup>)
+
*[[Vinorelbine (Navelbine)]] by the following BSA-based criteria:
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 3 to 6
+
**0.25-0.29 m<sup>2</sup> BSA: 4 mg IV push over 6 to 10 minutes on days 1, 8, and 15
−
'''One course of up to 90 days'''
+
**0.3-0.34 m<sup>2</sup> BSA: 6 mg IV push over 6 to 10 minutes on days 1, 8, and 15
−
</div>
+
**0.35-0.39 m<sup>2</sup> BSA: 7.5 mg IV push over 6 to 10 minutes on days 1, 8, and 15
−
<div class="toccolours" style="background-color:#cbd5e7">
+
**0.4-0.44 m<sup>2</sup> BSA: 9 mg IV push over 6 to 10 minutes on days 1, 8, and 15
−
====Subsequent treatment====
+
**0.45-0.49 m<sup>2</sup> BSA: 11 mg IV push over 6 to 10 minutes on days 1, 8, and 15
−
*[[#Arsenic_trioxide.2C_then_ATRA_.26_Daunorubicin|Arsenic trioxide, then ATRA & daunorubicin]] consolidation versus [[#ATRA_.26_Daunorubicin|ATRA & daunorubicin]] consolidation
+
**0.5-0.54 m<sup>2</sup> BSA: 12 mg IV push over 6 to 10 minutes on days 1, 8, and 15
 +
**0.55-0.59 m<sup>2</sup> BSA: 14 mg IV push over 6 to 10 minutes on days 1, 8, and 15
 +
**≥ 0.6 m<sup>2</sup> BSA: 25 mg/m<sup>2</sup> IV push over 6 to 10 minutes on days 1, 8, and 15
 +
*[[Cyclophosphamide (Cytoxan)]] 25 mg/m<sup>2</sup> PO once daily on days 1 through 28
 +
**Dose rounded to the nearest 25 mg capsule
 +
'''28-day cycle'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''EAPLG APL 2000:''' Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; EAPLG. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. [https://doi.org/10.1200/jco.2006.08.1596 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17116939 PubMed] NCT00591526
+
# '''Vinorelbine and low dose cyclophosphamide maintenance therapy:''' Vinorelbine and low dose cyclophosphamide maintenance therapy: Bisogno G, De Salvo GL, Bergeron C, Gallego Melcons s, Merks JH, Kelsey A, Martelli H, Minard-Colin V, Orbach D, Glosli H, Chisholm J, Casanova M, Zanetti I, Devalck C, Ben-Arush M, Mudry P, Ferman S, Jenney M, Ferrari A. Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 tial. Lancet Oncol. 2019 Nov;20(11):1566-1575. [https://doi.org/10.1016/S1470-2045(19)30617-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31562043/ PubMed]  
−
## '''Pooled subgroup analysis:''' Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://www.bloodjournal.org/content/111/3/1078.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17975017 PubMed]
+
# '''COG ARST1431:''' [https://clinicaltrials.gov/ct2/show/NCT02567435 NCT02567435]
−
# '''C9710:''' Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. [http://www.bloodjournal.org/content/116/19/3751.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20705755 PubMed] NCT00003934
+
==COG ARST1431 Protocol B (VAC/VI Plus TORI)==
−
 
 
−
==ATRA, Cytarabine, Idarubicin {{#subobject:e4a23d|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:124ac5|Variant=1}}===
+
===Protocol, Cycles 1-4 (Weeks 1 through 12)===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6269295/ Adès et al. 2018 (APL 2006)]
 
−
|2006-2013
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day, starting on day 1 and continuing until complete remission
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cytarabine (Ara-C)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 3 (total dose: 1400 mg/m<sup>2</sup>)
+
*[[Temsirolimus (Torisel)]] by the following weight-based criteria:
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once per day on days 3 to 5
+
**< 10 kg: 0.5 mg/kg IV over 30 to 60 minutes once weekly on day 1 of weeks 1 through 12
−
'''One course until CR'''
+
**> 10 kg: 15 mg/m<sup>2</sup> (maximum dose of 25 mg) IV on day 1 of weeks 1 through 12
−
</div>
+
*[[Vincristine (Oncovin)]] by the following BSA-based criteria:
−
<div class="toccolours" style="background-color:#cbd5e7">
+
**0.25-0.29 m<sup>2</sup> BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
====Subsequent treatment====
+
**0.3-0.34 m<sup>2</sup> BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
*Patients with baseline WBC less than 10 x 10<sup>9</sup>/L: [[#Cytarabine_.26_Idarubicin|Cytarabine & Idarubicin]] versus Arsenic trioxide & Idarubicin versus ATRA & Idarubicin consolidation
+
**0.35-0.39 m<sup>2</sup> BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
*Patients with baseline WBC greater than 10 x 10<sup>9</sup>/L: [[#Cytarabine_.26_Idarubicin|Cytarabine & Idarubicin]] versus Arsenic trioxide, Cytarabine, Idarubicin consolidation
+
**0.4-0.44 m<sup>2</sup> BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
</div></div>
+
**0.45-0.49 m<sup>2</sup> BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
===References===
+
**0.5-0.54 m<sup>2</sup> BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
# '''APL 2006:''' Adès L, Thomas X, Guerci Bresler A, Raffoux E, Spertini O, Vey N, Marchand T, Récher C, Pigneux A, Girault S, Deconinck E, Gardin C, Tournilhac O, Lambert JF, Chevallier P, de Botton S, Lejeune J, Dombret H, Chevret S, Fenaux P; French Belgian Swiss APL group. Arsenic trioxide is required in the treatment of newly diagnosed acute promyelocytic leukemia: analysis of a randomized trial (APL 2006) by the French Belgian Swiss APL group. Haematologica. 2018 Dec;103(12):2033-9. Epub 2018 Jul 19. [http://www.haematologica.org/content/103/12/2033 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6269295/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30026341 PubMed] NCT00378365
+
**0.55-0.59 m<sup>2</sup> BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
−
==ATRA & Daunorubicin {{#subobject:6c0f66|Regimen=1}}==
+
**≥ 0.6 m<sup>2</sup> BSA: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
 +
*[[Dactinomycin (Cosmegen)]] by the following weight-based criteria:
 +
**3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
 +
**4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
 +
**6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
 +
**7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
 +
**8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
 +
**10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
 +
**11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
 +
**12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
 +
**≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
 +
*[[Cyclophosphamide (Cytoxan)]] by the following BSA-based criteria:
 +
**0.25-0.29 m<sup>2</sup> BSA: 220 mg IV over 60 minutes on day 1 of weeks 1 and 7
 +
**0.3-0.34 m<sup>2</sup> BSA: 280 mg IV over 60 minutes on day 1 of weeks 1 and 7
 +
**0.35-0.39 m<sup>2</sup> BSA: 360 mg IV over 60 minutes on day 1 of weeks 1 and 7
 +
**0.4-0.44 m<sup>2</sup> BSA: 440 mg IV over 60 minutes on day 1 of weeks 1 and 7
 +
**0.45-0.49 m<sup>2</sup> BSA: 520 mg IV over 60 minutes on day 1 of weeks 1 and 7
 +
**0.5-0.54 m<sup>2</sup> BSA: 600 mg IV over 60 minutes on day 1 of weeks 1 and 7
 +
**0.55-0.59 m<sup>2</sup> BSA: 660 mg IV over 60 minutes on day 1 of weeks 1 and 7
 +
**≥ 0.6 m<sup>2</sup> BSA: 1200 mg/m<sup>2</sup> IV over 60 minutes on day 1 of weeks 1 and 7
 +
*[[Irinotecan (Camptosar)]] by the following BSA-based criteria:
 +
**0.25-0.29 m<sup>2</sup> BSA: 8 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
 +
**0.3-0.34 m<sup>2</sup> BSA: 12 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
 +
**0.35-0.39 m<sup>2</sup> BSA: 15 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
 +
**0.4-0.44 m<sup>2</sup> BSA: 18 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
 +
**0.45-0.49 m<sup>2</sup> BSA: 22 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
 +
**0.5-0.54 m<sup>2</sup> BSA: 24 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
 +
**0.55-0.59 m<sup>2</sup> BSA: 28 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
 +
**≥ 0.6 m<sup>2</sup> BSA: 50 mg/m<sup>2</sup> IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
 +
====Supportive Medications====
 +
*[[Mesna (Mesnex)]] by the following BSA-based criteria:
 +
[[Mesna (Mesnex)]] can also be given PO at twice the IV dose
 +
**0.25-0.29 m<sup>2</sup> BSA: 176 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.3-0.34 m<sup>2</sup> BSA: 224 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.35-0.39 m<sup>2</sup> BSA: 288 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.4-0.44 m<sup>2</sup> BSA: 352 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.45-0.49 m<sup>2</sup> BSA: 416 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.5-0.54 m<sup>2</sup> BSA: 480 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.55-0.59 m<sup>2</sup> BSA: 528 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**≥ 0.6 m<sup>2</sup> BSA: 960 mg/m<sup>2</sup> IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:aa790b|Variant=1}}===
+
===Protocol, Cycles 5-10 (Weeks 13 through 30)===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.08.1596 Adès et al. 2006 (EAPLG APL 2000)]
 
−
|2000-2004
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#ATRA.2C_Cytarabine.2C_Daunorubicin|ATRA, Cytarabine, Daunorubicin]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
''Note: This induction arm was a randomization for young (less than 60), low-risk (WBC count less than 10 x 10<sup>9</sup>/L) patients. Low-risk (WBC count less than 10 x 10<sup>9</sup>/L) older (greater than 60) patients received this regimen in a non-randomized fashion.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day, starting on day 1 and continuing until remission or maximum of 90 days
 
−
====Chemotherapy====
 
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m<sup>2</sup> IV once per day on days 3 to 5
 
−
'''One course of up to 90 days'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Daunorubicin_monotherapy|Daunorubicin]] consolidation
 
−
</div></div>
 
−
===References===
 
−
# '''EAPLG APL 2000:''' Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; EAPLG. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. [https://doi.org/10.1200/jco.2006.08.1596 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17116939 PubMed] NCT00591526
 
−
## '''Pooled subgroup analysis:''' Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://www.bloodjournal.org/content/111/3/1078.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17975017 PubMed]
 
−
 
 
−
==ATRA & Idarubicin {{#subobject:772861|Regimen=1}}==
 
−
AIDA: '''<u>A</u>'''TRA, '''<u>IDA</u>'''rubicin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:71cfae|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/88/4/1390.long Avvisati et al. 1996 (GIMEMA AIDA)]
 
−
|1993
 
−
| style="background-color:#91cf61" |Pilot
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/90/3/1014.long Mandelli et al. 1997 (GIMEMA AIDA 0493)]
 
−
|1993-1996
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/4/1237.full Sanz et al. 2003 (PETHEMA LPA96)]
 
−
|1996-1999
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.2011.08593.x Latagliata et al. 2011 (GIMEMA AIDA 0493 amended protocol)]
 
−
|1997-2004
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/4/1237.full Sanz et al. 2003 (PETHEMA LPA99)]
 
−
|1999-2002
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/116/17/3171.long Lo-Coco et al. 2010 (GIMEMA AIDA-2000)]
 
−
|2000-2006
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/115/25/5137.long Sanz et al. 2010 (PETHEMA LPA2005)]
 
−
|2005-2009
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1300874 Lo-Coco et al. 2013 (GIMEMA/DSIL APL0406)]
 
−
|2007-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Arsenic_trioxide_.26_ATRA|Arsenic trioxide & ATRA]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00193-X Burnett et al. 2015 (UK NCRI AML17)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Arsenic_trioxide_.26_ATRA|Arsenic trioxide & ATRA]]
 
−
|
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of QoL
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for GIMEMA/DSIL APL0406 is based on the 2019 update.''<br>
 
−
''Note: this is the same induction used in '''multiple''' protocols. Consolidation and maintenance differ, follow the appropriate links below.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[All-trans retinoic acid (ATRA)]] starting day 1 and continuing until remission or maximum of 90 days, by the following criteria:
 
−
**21 or older: 22.5 mg/m<sup>2</sup> PO twice per day
 
−
**Less than 20 years old: 12.5 mg/m<sup>2</sup> PO twice per day
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Idarubicin (Idamycin)]] by the following criteria:
+
*[[Temsirolimus (Torisel)]] by the following weight-based criteria:
−
**Up to age 70: 12 mg/m<sup>2</sup> IV bolus once per day on days 2, 4, 6, 8
+
**< 10 kg: 0.5 mg/kg IV over 30 to 60 minutes once weekly on day 1 of weeks 21 through 30
−
**Older than 70 years old: 12 mg/m<sup>2</sup> IV bolus once per day on days 2, 4, 6
+
**> 10 kg: 15 mg/m<sup>2</sup> (maximum dose of 25 mg) IV on day 1 of weeks 21 through 30
−
'''One course of up to 90 days'''
+
*[[Vincristine (Oncovin)]] by the following BSA-based criteria:
−
</div>
+
**0.25-0.29 m<sup>2</sup> BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
<div class="toccolours" style="background-color:#cbd5e7">
+
**0.3-0.34 m<sup>2</sup> BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
====Subsequent treatment====
+
**0.35-0.39 m<sup>2</sup> BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
''Once CR was achieved, patients proceeded to consolidation by the following study-specific criteria:''
+
**0.4-0.44 m<sup>2</sup> BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
*PETHEMA LPA96: [[#Idarubicin.2C_then_Mitoxantrone.2C_then_Idarubicin|Idarubicin, then mitoxantrone, then idarubicin]] consolidation
+
**0.45-0.49 m<sup>2</sup> BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
*GIMEMA AIDA & AIDA 0493: [[#Cytarabine_.26_Idarubicin.2C_then_Etoposide_.26_Mitoxantrone.2C_then_Cytarabine.2C_Idarubicin.2C_Thioguanine|Cytarabine & idarubicin, then etoposide & mitoxantrone, then cytarabine, idarubicin, thioguanine]] consolidation
+
**0.5-0.54 m<sup>2</sup> BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
*PETHEMA LPA99: risk-adapted therapy by the following criteria:
+
**0.55-0.59 m<sup>2</sup> BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
**<u>Low-risk</u> patients: [[#Idarubicin.2C_then_Mitoxantrone.2C_then_Idarubicin|Idarubicin, then mitoxantrone, then idarubicin]] consolidation
+
**≥ 0.6 m<sup>2</sup> BSA: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
−
**<u>Intermediate- and high-risk</u> patients: [[#Idarubicin.2C_then_Mitoxantrone.2C_then_Idarubicin.2C_with_ATRA|Idarubicin, then mitoxantrone, then idarubicin, with ATRA]] consolidation
+
*[[Dactinomycin (Cosmegen)]] by the following weight-based criteria:
−
*PETHEMA LPA2005: risk-adapted therapy by the following criteria:
+
**3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
**<u>High-risk</u> patients: [[#Cytarabine_.26_Idarubicin.2C_then_Mitoxantrone.2C_then_Cytarabine_.26_Idarubicin.2C_with_ATRA|Cytarabine & idarubicin, then mitoxantrone, then cytarabine & idarubicin, with ATRA]] consolidation
+
**4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
**<u>Intermediate- and low-risk</u> patients: [[#Idarubicin.2C_then_Mitoxantrone.2C_then_Idarubicin.2C_with_ATRA|Idarubicin, then mitoxantrone, then idarubicin, with ATRA]] consolidation
+
**6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
*AIDA 2000: risk-adapted therapy by the following criteria:
+
**7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
**<u>High-risk</u> patients: [[#Cytarabine_.26_Idarubicin.2C_then_Etoposide_.26_Mitoxantrone.2C_then_Cytarabine.2C_Idarubicin.2C_Thioguanine.2C_with_ATRA|Cytarabine & idarubicin, then etoposide & mitoxantrone, then cytarabine, idarubicin, thioguanine, with ATRA]] consolidation
+
**8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
**<u>Intermediate- and low-risk</u> patients: [[#Idarubicin.2C_then_Mitoxantrone.2C_then_Idarubicin.2C_with_ATRA|Idarubicin, then mitoxantrone, then idarubicin, with ATRA]] consolidation
+
**10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
*GIMEMA AIDA 0493 amended protocol: [[#Cytarabine_.26_Idarubicin|Cytarabine & idarubicin]] consolidation
+
**11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
*GIMEMA/DSIL APL0406 and UK NCRI AML17: [[#Idarubicin.2C_then_Mitoxantrone.2C_then_Idarubicin.2C_with_ATRA|Idarubicin, then mitoxantrone, then idarubicin, with ATRA]] consolidation
+
**12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
</div></div>
+
**≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
−
===References===
+
Give week 13 dose of [[Dactinomycin (Cosmegen)]] before beginning radiation therapy
−
# '''GIMEMA AIDA:''' Avvisati G, Lo Coco F, Diverio D, Falda M, Ferrara F, Lazzarino M, Russo D, Petti MC, Mandelli F. AIDA (all-trans retinoic acid + idarubicin) in newly diagnosed acute promyelocytic leukemia: a Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) pilot study. Blood. 1996 Aug 15;88(4):1390-8. [http://www.bloodjournal.org/content/88/4/1390.long link to full article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8695858 PubMed]
+
*[[Cyclophosphamide (Cytoxan)]] by the following BSA-based criteria:
−
# '''GIMEMA AIDA 0493:''' Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C, Broccia G, Cerri R, Falda M, Fioritoni G, Leoni F, Liso V, Petti MC, Rodeghiero F, Saglio G, Vegna ML, Visani G, Jehn U, Willemze R, Muus P, Pelicci PG, Biondi A, Lo Coco F; Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto; Associazione Italiana di Ematologia ed Oncologia Pediatrica. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Blood. 1997 Aug 1;90(3):1014-21. [http://www.bloodjournal.org/content/90/3/1014.long link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/9242531 PubMed]
+
**0.25-0.29 m<sup>2</sup> BSA: 220 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
−
## '''Update:''' Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA; AIEOP; EORTC. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. [http://www.bloodjournal.org/content/117/18/4716.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21385856 PubMed]
+
**0.3-0.34 m<sup>2</sup> BSA: 280 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
−
# '''PETHEMA LPA96:''' Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. [http://www.bloodjournal.org/content/103/4/1237.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14576047 PubMed]
+
**0.35-0.39 m<sup>2</sup> BSA: 360 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
−
## '''Pooled subgroup analysis:''' Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://www.bloodjournal.org/content/111/3/1078.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17975017 PubMed]
+
**0.4-0.44 m<sup>2</sup> BSA: 440 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
−
# '''PETHEMA LPA99:''' Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. [http://www.bloodjournal.org/content/103/4/1237.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14576047 PubMed] NCT00465933
+
**0.45-0.49 m<sup>2</sup> BSA: 520 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
−
## '''Pooled subgroup analysis:''' Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://www.bloodjournal.org/content/111/3/1078.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17975017 PubMed]
+
**0.5-0.54 m<sup>2</sup> BSA: 600 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
−
# '''PETHEMA LPA2005:''' Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA; HOVON. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. Epub 2010 Apr 14. [http://www.bloodjournal.org/content/115/25/5137.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20393132 PubMed] NCT00408278
+
**0.55-0.59 m<sup>2</sup> BSA: 660 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
−
# '''GIMEMA AIDA-2000:''' Lo-Coco F, Avvisati G, Vignetti M, Breccia M, Gallo E, Rambaldi A, Paoloni F, Fioritoni G, Ferrara F, Specchia G, Cimino G, Diverio D, Borlenghi E, Martinelli G, Di Raimondo F, Di Bona E, Fazi P, Peta A, Bosi A, Carella AM, Fabbiano F, Pogliani EM, Petti MC, Amadori S, Mandelli F; GIMEMA. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood. 2010 Oct 8;116(17):3171-9. Epub 2010 Jul 19. [http://www.bloodjournal.org/content/116/17/3171.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20644121 PubMed] NCT001064570
+
**≥ 0.6 m<sup>2</sup> BSA: 1200 mg/m<sup>2</sup> IV over 60 minutes on day 1 of weeks 13, 22, 28
−
# '''GIMEMA AIDA 0493 amended protocol:''' Latagliata R, Breccia M, Fazi P, Vignetti M, Di Raimondo F, Sborgia M, Vincelli D, Candoni A, Salvi F, Rupoli S, Martinelli G, Kropp MG, Tonso A, Venditti A, Melillo L, Cimino G, Petti MC, Avvisati G, Lo-Coco F, Mandelli F; GIMEMA Acute Leukaemia Working Party. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia: long-term results and prognostic factors. Br J Haematol. 2011 Sep;154(5):564-8. Epub 2011 Jul 14. [https://doi.org/10.1111/j.1365-2141.2011.08593.x link to full article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21751984 PubMed]
+
*[[Irinotecan (Camptosar)]] by the following BSA-based criteria:
−
# '''GIMEMA/DSIL APL0406:''' Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. [https://doi.org/10.1056/NEJMoa1300874 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23841729 PubMed] NCT00482833
+
**0.25-0.29 m<sup>2</sup> BSA: 8 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
−
## '''HRQoL analysis:''' Efficace F, Mandelli F, Avvisati G, Cottone F, Ferrara F, Di Bona E, Specchia G, Breccia M, Levis A, Sica S, Finizio O, Kropp MG, Fioritoni G, Cerqui E, Vignetti M, Amadori S, Schlenk RF, Platzbecker U, Lo-Coco F. Randomized phase III trial of retinoic acid and arsenic trioxide versus retinoic acid and chemotherapy in patients with acute promyelocytic leukemia: health-related quality-of-life outcomes. J Clin Oncol. 2014 Oct 20;32(30):3406-12. Epub 2014 Sep 22. [https://doi.org/10.1200/JCO.2014.55.3453 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25245446 PubMed]
+
**0.3-0.34 m<sup>2</sup> BSA: 12 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
−
## '''Update:''' Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute promyelocytic leukemia: final results of the randomized Italian-German APL0406 trial. J Clin Oncol. 2017 Feb 20;35(6):605-612. Epub 2016 Oct 31. [https://doi.org/10.1200/JCO.2016.67.1982 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27400939 PubMed]
+
**0.35-0.39 m<sup>2</sup> BSA: 15 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
−
## '''Update:''' Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts CH, Hanel M, Rollig C, Schmitz N, Link H, Frairia C, Fozza C, Maria D'Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Voso MT, Ehninger G, Schlenk RF, Lo-Coco F. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial. Leukemia. 2020 Mar;34(3):914-918. Epub 2019 Oct 14. [https://doi.org/10.1038/s41375-019-0589-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31611624 PubMed]
+
**0.4-0.44 m<sup>2</sup> BSA: 18 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
−
# '''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Bowen D, Kell J, Knapper S, Morgan YG, Lok J, Grech A, Jones G, Khwaja A, Friis L, McMullin MF, Hunter A, Clark RE, Grimwade D; UK National Cancer Research Institute Acute Myeloid Leukaemia Working Group. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Oct;16(13):1295-305. Epub 2015 Sep 14. [https://doi.org/10.1016/S1470-2045(15)00193-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/26384238 PubMed] ISRCTN55675535
+
**0.45-0.49 m<sup>2</sup> BSA: 22 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
−
## '''Update:''' Russell N, Burnett A, Hills R, Betteridge S, Dennis M, Jovanovic J, Dillon R, Grimwade D; NCRI AML Working Group. Attenuated arsenic trioxide plus ATRA therapy for newly diagnosed and relapsed APL: long-term follow-up of the AML17 trial. Blood. 2018 Sep 27;132(13):1452-1454. Epub 2018 Aug 10. [https://doi.org/10.1182/blood-2018-05-851824 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6225356/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30097508 PubMed]
+
**0.5-0.54 m<sup>2</sup> BSA: 24 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
−
=Consolidation after upfront therapy=
+
**0.55-0.59 m<sup>2</sup> BSA: 28 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
−
==Arsenic trioxide monotherapy {{#subobject:f1814c|Regimen=1}}==
+
**≥ 0.6 m<sup>2</sup> BSA: 50 mg/m<sup>2</sup> IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
 +
====Supportive Medications====
 +
*[[Mesna (Mesnex)]] by the following BSA-based criteria:
 +
[[Mesna (Mesnex)]] can also be given PO at twice the IV dose
 +
**0.25-0.29 m<sup>2</sup> BSA: 176 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.3-0.34 m<sup>2</sup> BSA: 224 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.35-0.39 m<sup>2</sup> BSA: 288 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.4-0.44 m<sup>2</sup> BSA: 352 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.45-0.49 m<sup>2</sup> BSA: 416 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.5-0.54 m<sup>2</sup> BSA: 480 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.55-0.59 m<sup>2</sup> BSA: 528 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**≥ 0.6 m<sup>2</sup> BSA: 960 mg/m<sup>2</sup> IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, adult dosing {{#subobject:7befb3|Variant=1}}===
+
===Protocol, Cycles 11-14 (Weeks 31 through 42)===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1182/blood-2005-08-3532 Mathews et al. 2006]
 
−
|1998-2004
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Arsenic_trioxide_monotherapy|Arsenic trioxide]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] 10 mg IV over 2 to 3 hours once per day
 
−
'''28-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Mathews et al. 2006, patients remaining in CR: [[#Arsenic_trioxide_monotherapy_3|Arsenic trioxide]] maintenance
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, pediatric dosing {{#subobject:7bebu3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1182/blood-2005-08-3532 Mathews et al. 2006]
 
−
|1998-2004
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Arsenic_trioxide_monotherapy|Arsenic trioxide]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV over 2 to 3 hours once per day
 
−
'''28-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients remaining in CR: [[#Arsenic_trioxide_monotherapy_3|Arsenic trioxide]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# Mathews V, George B, Lakshmi KM, Viswabandya A, Bajel A, Balasubramanian P, Shaji RV, Srivastava VM, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006 Apr 1;107(7):2627-32. Epub 2005 Dec 13. [https://doi.org/10.1182/blood-2005-08-3532 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16352810 PubMed]
 
−
## '''Update:''' Mathews V, George B, Chendamarai E, Lakshmi KM, Desire S, Balasubramanian P, Viswabandya A, Thirugnanam R, Abraham A, Shaji RV, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol. 2010 Aug 20;28(24):3866-71. Epub 2010 Jul 19. [https://doi.org/10.1200/jco.2010.28.5031 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20644086 PubMed]
 
−
==Arsenic trioxide, then ATRA & Daunorubicin {{#subobject:e333b6|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:24bfd3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ Powell et al. 2010 (C9710)]
 
−
|1999-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#ATRA_.26_Daunorubicin|ATRA & Daunorubicin]]
 
−
| style="background-color:#1a9850" |Superior EFS
 
−
|-
 
−
|}
 
−
''Consolidation therapy starts within 2 to 4 weeks of hematologic remission.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#ATRA.2C_Cytarabine.2C_Daunorubicin|ATRA, cytarabine, daunorubicin]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy, part 1====
 
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
 
−
'''7-week cycles (5 weeks of therapy, then 2 weeks off), followed by:'''
 
−
====Targeted therapy, part 2====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 7
 
−
====Chemotherapy, part 2====
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''39-day cycle for 2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#ATRA_monotherapy_2|ATRA]] maintenance versus [[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# '''C9710:''' Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. [http://www.bloodjournal.org/content/116/19/3751.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20705755 PubMed] NCT00003934
 
−
==Arsenic trioxide & ATRA {{#subobject:7ce78a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:a5626f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/107/9/3469.long Estey et al. 2005]
 
−
|2002-2005
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1300874 Lo-Coco et al. 2013 (GIMEMA/DSIL APL0406)]
 
−
|2007-2013
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''Note: There is no maintenance in this protocol.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Arsenic_trioxide_.26_ATRA|Arsenic trioxide & ATRA]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] as follows:
 
−
**Cycles 1, 3, 5, 7: 0.15 mg/kg IV over 1 to 2 hours once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''28-cycle for 7 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol variant #2 {{#subobject:575577|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1182/blood-2012-02-410746 Iland et al. 2012 (ALLG APML4)]
 
−
|2004-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Consolidation starts 3 to 4 weeks after completion of induction.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Arsenic_trioxide.2C_ATRA.2C_Idarubicin|Arsenic trioxide, ATRA, idarubicin]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy, part 1====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 28
 
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV once per day on days 1 to 28
 
−
'''4-week course'''; after 3 to 4 weeks, proceed to consolidation cycle 2
 
−
====Targeted therapy, part 2====
 
−
''Given 3 to 4 weeks after completion of consolidation cycle 1.''
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 7, 15 to 21, 29 to 35
 
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
 
−
'''5-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]] maintenance, after 3 to 4 weeks
 
−
</div></div>
 
−
===References===
 
−
# Estey E, Garcia-Manero G, Ferrajoli A, Faderl S, Verstovsek S, Jones D, Kantarjian H. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006 May 1;107(9):3469-73. Epub 2005 Dec 22. [http://www.bloodjournal.org/content/107/9/3469.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16373661 PubMed]
 
−
# '''ALLG APML4:''' Iland HJ, Bradstock K, Supple SG, Catalano A, Collins M, Hertzberg M, Browett P, Grigg A, Firkin F, Hugman A, Reynolds J, Di Iulio J, Tiley C, Taylor K, Filshie R, Seldon M, Taper J, Szer J, Moore J, Bashford J, Seymour JF; Australasian Leukaemia and Lymphoma Group. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood. 2012 Aug 23;120(8):1570-80. Epub 2012 Jun 19. [https://doi.org/10.1182/blood-2012-02-410746 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22715121 PubMed] ACTRN12605000070639
 
−
# '''GIMEMA/DSIL APL0406:''' Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. [https://doi.org/10.1056/NEJMoa1300874 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23841729 PubMed] NCT00482833
 
−
## '''HRQoL analysis:''' Efficace F, Mandelli F, Avvisati G, Cottone F, Ferrara F, Di Bona E, Specchia G, Breccia M, Levis A, Sica S, Finizio O, Kropp MG, Fioritoni G, Cerqui E, Vignetti M, Amadori S, Schlenk RF, Platzbecker U, Lo-Coco F. Randomized phase III trial of retinoic acid and arsenic trioxide versus retinoic acid and chemotherapy in patients with acute promyelocytic leukemia: health-related quality-of-life outcomes. J Clin Oncol. 2014 Oct 20;32(30):3406-12. Epub 2014 Sep 22. [https://doi.org/10.1200/JCO.2014.55.3453 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25245446 PubMed]
 
−
## '''Update:''' Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute promyelocytic leukemia: final results of the randomized Italian-German APL0406 trial. J Clin Oncol. 2017 Feb 20;35(6):605-612. Epub 2016 Oct 31. [https://doi.org/10.1200/JCO.2016.67.1982 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27400939 PubMed]
 
−
## '''Update:''' Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts CH, Hanel M, Rollig C, Schmitz N, Link H, Frairia C, Fozza C, Maria D'Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Voso MT, Ehninger G, Schlenk RF, Lo-Coco F. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial. Leukemia. 2020 Mar;34(3):914-918. Epub 2019 Oct 14. [https://doi.org/10.1038/s41375-019-0589-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31611624 PubMed]
 
−
# '''UK NCRI AML17:''' Burnett AK, Russell NH, Hills RK, Bowen D, Kell J, Knapper S, Morgan YG, Lok J, Grech A, Jones G, Khwaja A, Friis L, McMullin MF, Hunter A, Clark RE, Grimwade D; UK National Cancer Research Institute Acute Myeloid Leukaemia Working Group. Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Oct;16(13):1295-305. Epub 2015 Sep 14. [https://doi.org/10.1016/S1470-2045(15)00193-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/26384238 PubMed] ISRCTN55675535
 
−
## '''Update:''' Russell N, Burnett A, Hills R, Betteridge S, Dennis M, Jovanovic J, Dillon R, Grimwade D; NCRI AML Working Group. Attenuated arsenic trioxide plus ATRA therapy for newly diagnosed and relapsed APL: long-term follow-up of the AML17 trial. Blood. 2018 Sep 27;132(13):1452-1454. Epub 2018 Aug 10. [https://doi.org/10.1182/blood-2018-05-851824 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6225356/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30097508 PubMed]
 
−
==ATRA & Daunorubicin {{#subobject:5d419b|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b8d811|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ Powell et al. 2010 (C9710)]
 
−
|1999-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Arsenic_trioxide.2C_then_ATRA_.26_Daunorubicin|Arsenic trioxide, then ATRA & Daunorubicin]]
 
−
| style="background-color:#d73027" |Inferior EFS
 
−
|-
 
−
|}
 
−
''Consolidation therapy starts within 2 to 4 weeks of hematologic remission.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#ATRA.2C_Cytarabine.2C_Daunorubicin|ATRA, cytarabine, daunorubicin]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 7
 
−
====Chemotherapy====
 
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''39-day cycle for 2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#ATRA_monotherapy_2|ATRA]] maintenance versus [[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# '''C9710:''' Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. [http://www.bloodjournal.org/content/116/19/3751.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20705755 PubMed] NCT00003934
 
−
==Cytarabine & Daunorubicin {{#subobject:f3ec97|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:198c4e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.08.1596 Adès et al. 2006 (EAPLG APL 2000)]
 
−
|2000-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Daunorubicin_monotherapy|Daunorubicin]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#ATRA.2C_Cytarabine.2C_Daunorubicin|ATRA, cytarabine, daunorubicin]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] as follows:
 
−
**Cycle 1: 200 mg/m<sup>2</sup>/day IV continuous infusion over 7 days, started on day 1 (total dose: 1400 mg/m<sup>2</sup>)
 
−
**Cycle 2, younger than 60 & low-risk (WBC count less than 10 x 10<sup>9</sup>/L) or older than 60 & high-risk (WBC count greater than 10 x 10<sup>9</sup>/L): 1000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 4 (total dose: 8000 mg/m<sup>2</sup>)
 
−
**Cycle 2, younger than 60 & high-risk (WBC count greater than 10 x 10<sup>9</sup>/L): 2000 mg/m<sup>2</sup> IV every 12 hours on days 1 to 5 (total dose: 20,000 mg/m<sup>2</sup>)
 
−
*[[Daunorubicin (Cerubidine)]] as follows:
 
−
**Cycle 1: 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
**Cycle 2: 45 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====CNS therapy, high-risk (WBC count greater than 10 x 10<sup>9</sup>/L) patients====
 
−
*5 doses of intrathecal chemotherapy with [[Methotrexate (MTX)]] 15 mg IT, [[Cytarabine (Ara-C)]] 50 mg IT, and corticosteroids given during consolidation
 
−
'''2 cycles (length not specified)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# '''EAPLG APL 2000:''' Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; EAPLG. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. [https://doi.org/10.1200/jco.2006.08.1596 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17116939 PubMed] NCT00591526
 
−
## '''Pooled subgroup analysis:''' Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://www.bloodjournal.org/content/111/3/1078.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17975017 PubMed]
 
−
==Cytarabine & Idarubicin {{#subobject:b76471|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f5d960|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.2011.08593.x Latagliata et al. 2011 (GIMEMA AIDA 0493 amended protocol)]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
''This consolidation protocol was intended for patients older than 60.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#ATRA_.26_Idarubicin|ATRA & idarubicin]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 4, '''given first'''
+
*[[Temsirolimus (Torisel)]] by the following weight-based criteria:
−
*[[Idarubicin (Idamycin)]] 5 mg/m<sup>2</sup> IV once per day on days 1 to 4, '''given second, 3 hours after cytarabine infusion complete'''
+
**< 10 kg: 0.5 mg/kg IV over 30 to 60 minutes once weekly on day 1 of weeks 31 through 42
−
'''4-day course'''
+
**> 10 kg: 15 mg/m<sup>2</sup> (maximum dose of 25 mg) IV on day 1 of weeks 31 through 42
−
</div>
+
*[[Vincristine (Oncovin)]] by the following BSA-based criteria:
−
<div class="toccolours" style="background-color:#cbd5e7">
+
**0.25-0.29 m<sup>2</sup> BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
====Subsequent treatment====
+
**0.3-0.34 m<sup>2</sup> BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
*[[#ATRA_monotherapy_2|ATRA]] maintenance
+
**0.35-0.39 m<sup>2</sup> BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
</div></div>
+
**0.4-0.44 m<sup>2</sup> BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
===References===
+
**0.45-0.49 m<sup>2</sup> BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
# '''GIMEMA AIDA 0493 amended protocol:''' Latagliata R, Breccia M, Fazi P, Vignetti M, Di Raimondo F, Sborgia M, Vincelli D, Candoni A, Salvi F, Rupoli S, Martinelli G, Kropp MG, Tonso A, Venditti A, Melillo L, Cimino G, Petti MC, Avvisati G, Lo-Coco F, Mandelli F; GIMEMA Acute Leukaemia Working Party. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia: long-term results and prognostic factors. Br J Haematol. 2011 Sep;154(5):564-8. Epub 2011 Jul 14. [https://doi.org/10.1111/j.1365-2141.2011.08593.x link to full article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21751984 PubMed]
+
**0.5-0.54 m<sup>2</sup> BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
==Cytarabine & Idarubicin, then Etoposide & Mitoxantrone, then Cytarabine, Idarubicin, Thioguanine {{#subobject:cb4263|Regimen=1}}==
+
**0.55-0.59 m<sup>2</sup> BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
<div class="toccolours" style="background-color:#eeeeee">
+
**≥ 0.6 m<sup>2</sup> BSA: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
−
===Protocol {{#subobject:13180d|Variant=1}}===
+
*[[Dactinomycin (Cosmegen)]] by the following weight-based criteria:
−
{| class="wikitable" style="width: 60%; text-align:center;"
+
**3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
−
!style="width: 33%"|Study
+
**4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
−
!style="width: 33%"|Years of enrollment
+
**6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
−
|-
+
**8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
−
|[http://www.bloodjournal.org/content/100/9/3141.long Avvisati et al. 2002 (GIMEMA LAP 0389)]
+
**10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
−
|1989-1993
+
**11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
+
**12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
−
|-
+
**≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
−
|[http://www.bloodjournal.org/content/88/4/1390.long Avvisati et al. 1996 (GIMEMA AIDA)]
+
*[[Cyclophosphamide (Cytoxan)]] by the following BSA-based criteria:
−
|1993
+
**0.25-0.29 m<sup>2</sup> BSA: 220 mg IV over 60 minutes on day 1 of weeks 34, 40
−
| style="background-color:#91cf61" |Pilot
+
**0.3-0.34 m<sup>2</sup> BSA: 280 mg IV over 60 minutes on day 1 of weeks 34, 40
−
|-
+
**0.35-0.39 m<sup>2</sup> BSA: 360 mg IV over 60 minutes on day 1 of weeks 34, 40
−
|[http://www.bloodjournal.org/content/90/3/1014.long Mandelli et al. 1997 (GIMEMA AIDA 0493)]
+
**0.4-0.44 m<sup>2</sup> BSA: 440 mg IV over 60 minutes on day 1 of weeks 34, 40
−
|1993-1996
+
**0.45-0.49 m<sup>2</sup> BSA: 520 mg IV over 60 minutes on day 1 of weeks 34, 40
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
+
**0.5-0.54 m<sup>2</sup> BSA: 600 mg IV over 60 minutes on day 1 of weeks 34, 40
−
|-
+
**0.55-0.59 m<sup>2</sup> BSA: 660 mg IV over 60 minutes on day 1 of weeks 34, 40
−
|}
+
**≥ 0.6 m<sup>2</sup> BSA: 1200 mg/m<sup>2</sup> IV over 60 minutes on day 1 of weeks 34, 40
−
''Note that the consolidation portion of the AIDA 0493 protocol is only described in Avvisati et al. 1996.''
+
*[[Irinotecan (Camptosar)]] by the following BSA-based criteria:
−
<div class="toccolours" style="background-color:#cbd5e8">
+
**0.25-0.29 m<sup>2</sup> BSA: 8 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
−
====Preceding treatment====
+
**0.3-0.34 m<sup>2</sup> BSA: 12 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
−
*GIMEMA LAP 0389: [[#Idarubicin_monotherapy_88|Idarubicin]] induction versus [[#Cytarabine_.26_Idarubicin_88|cytarabine & idarubicin]] induction (neither with ATRA; no longer standard of care)
+
**0.35-0.39 m<sup>2</sup> BSA: 15 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
−
*GIMEMA AIDA & AIDA 0493: [[#ATRA_.26_Idarubicin|ATRA & idarubicin]] induction
+
**0.4-0.44 m<sup>2</sup> BSA: 18 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
−
</div>
+
**0.45-0.49 m<sup>2</sup> BSA: 22 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
−
<div class="toccolours" style="background-color:#b3e2cd">
+
**0.5-0.54 m<sup>2</sup> BSA: 24 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
−
====Chemotherapy, part 1====
+
**0.55-0.59 m<sup>2</sup> BSA: 28 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 6 hours once per day on days 1 to 4, '''given first'''
+
**≥ 0.6 m<sup>2</sup> BSA: 50 mg/m<sup>2</sup> IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
−
*[[Idarubicin (Idamycin)]] 5 mg/m<sup>2</sup> IV once per day on days 1 to 4, '''given second, 3 hours after cytarabine infusion complete'''
+
====Supportive Medications====
−
'''4-day course; next course to begin "at recovery from the previous one, when polymorphonuclear cells numbered 1500/uL or more and platelets numbered 100 x 10<sup>9</sup>/L or more."'''
+
*[[Mesna (Mesnex)]] by the following BSA-based criteria:
−
====Chemotherapy, part 2====
+
[[Mesna (Mesnex)]] can also be given PO at twice the IV dose
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 45 to 60 minutes once per day on days 1 to 5, '''given second, 12 hours after start of mitoxantrone'''
+
**0.25-0.29 m<sup>2</sup> BSA: 176 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 5, '''given first'''
+
**0.3-0.34 m<sup>2</sup> BSA: 224 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
'''5-day course; next course to begin "at recovery from the previous one, when polymorphonuclear cells numbered 1500/uL or more and platelets numbered 100 x 10<sup>9</sup>/L or more."'''
+
**0.35-0.39 m<sup>2</sup> BSA: 288 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
====Chemotherapy, part 3====
+
**0.4-0.44 m<sup>2</sup> BSA: 352 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
*[[Cytarabine (Ara-C)]] 150 mg/m<sup>2</sup> SC every 8 hours on days 1 to 5
+
**0.45-0.49 m<sup>2</sup> BSA: 416 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
*[[Idarubicin (Idamycin)]] by the following study-specific criteria:
+
**0.5-0.54 m<sup>2</sup> BSA: 480 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
**GIMEMA LAP 0389: 5 mg/m<sup>2</sup> IV once on day 1
+
**0.55-0.59 m<sup>2</sup> BSA: 528 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
**GIMEMA AIDA & AIDA 0493: 12 mg/m<sup>2</sup> IV once on day 1
+
**≥ 0.6 m<sup>2</sup> BSA: 960 mg/m<sup>2</sup> IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
−
*[[Thioguanine (Tabloid)]] 70 mg/m<sup>2</sup> PO every 8 hours on days 1 to 5
 
−
'''5-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*GIMEMA LAP 0389: [[#Mercaptopurine_.26_Methotrexate|6-MP & MTX]] maintenance versus [[Acute_promyelocytic_leukemia_-_null_regimens#Observation|no further treatment]]
 
−
*GIMEMA AIDA 0493: [[#ATRA_monotherapy_2|ATRA]] maintenance versus [[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]] maintenance versus [[#Mercaptopurine_.26_Methotrexate|6-MP & MTX]] maintenance versus [[Acute_promyelocytic_leukemia_-_null_regimens#Observation|no further treatment]]
 
−
</div></div>
 
−
===References===
 
−
# '''GIMEMA AIDA:''' Avvisati G, Lo Coco F, Diverio D, Falda M, Ferrara F, Lazzarino M, Russo D, Petti MC, Mandelli F. AIDA (all-trans retinoic acid + idarubicin) in newly diagnosed acute promyelocytic leukemia: a Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) pilot study. Blood. 1996 Aug 15;88(4):1390-8. [http://www.bloodjournal.org/content/88/4/1390.long link to full article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8695858 PubMed]
 
−
# '''GIMEMA AIDA 0493:''' Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C, Broccia G, Cerri R, Falda M, Fioritoni G, Leoni F, Liso V, Petti MC, Rodeghiero F, Saglio G, Vegna ML, Visani G, Jehn U, Willemze R, Muus P, Pelicci PG, Biondi A, Lo Coco F; Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto; Associazione Italiana di Ematologia ed Oncologia Pediatrica. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Blood. 1997 Aug 1;90(3):1014-21. [http://www.bloodjournal.org/content/90/3/1014.long link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/9242531 PubMed]
 
−
## '''Update:''' Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA; AIEOP; EORTC. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. [http://www.bloodjournal.org/content/117/18/4716.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21385856 PubMed]
 
−
# '''GIMEMA LAP 0389:''' Avvisati G, Petti MC, Lo-Coco F, Vegna ML, Amadori S, Baccarani M, Cantore N, Di Bona E, Ferrara F, Fioritoni G, Gallo E, Invernizzi R, Lazzarino M, Liso V, Mariani G, Ricciuti F, Selleri C, Sica S, Veneri D, Mandelli F; GIMEMA. Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up. Blood. 2002 Nov 1;100(9):3141-6. [http://www.bloodjournal.org/content/100/9/3141.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12384411 PubMed]
 
−
==Cytarabine & Idarubicin, then Etoposide & Mitoxantrone, then Cytarabine, Idarubicin, Thioguanine, with ATRA {{#subobject:632192|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:6e3780|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/116/17/3171.long Lo-Coco et al. 2010 (GIMEMA AIDA-2000)]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
''This is risk-adapted therapy for <u>high-risk</u> patients in '''AIDA-2000'''. The authors were unclear about how many days were between each part of consolidation therapy.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#ATRA_.26_Idarubicin|ATRA & idarubicin]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy, part 1====
 
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m<sup>2</sup>/day PO for a total of 15 days
 
−
====Chemotherapy, part 1====
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 4
 
−
*[[Idarubicin (Idamycin)]] 5 mg/m<sup>2</sup> IV once per day on days 1 to 4
 
−
'''4-day course (see note), followed by:'''
 
−
====Targeted therapy, part 2====
 
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m<sup>2</sup>/day PO for a total of 15 days
 
−
====Chemotherapy, part 2====
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
'''5-day course (see note), followed by:'''
 
−
====Targeted therapy, part 3====
 
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m<sup>2</sup>/day PO for a total of 15 days
 
−
====Chemotherapy, part 3====
 
−
*[[Cytarabine (Ara-C)]] 150 mg/m<sup>2</sup> SC every 8 hours on days 1 to 5 (total dose: 2250 mg/m<sup>2</sup>)
 
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Thioguanine (Tabloid)]] 70 mg/m<sup>2</sup> PO every 8 hours on days 1 to 5 (total dose: 1050 mg/m<sup>2</sup>)
 
−
'''5-day course (see note)'''
 
−
====CNS therapy, prophylaxis====
 
−
''It is not explicitly stated but presumably these are admixed and given together.''
 
−
*[[Methotrexate (MTX)]] 12 mg IT once prior to each consolidation cycle
 
−
*[[Methylprednisolone (Solumedrol)]] 40 mg IT once prior to each consolidation cycle
 
−
'''"Total of 3 cycles"'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA alternating with 6-MP, MTX]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# '''GIMEMA AIDA-2000:''' Lo-Coco F, Avvisati G, Vignetti M, Breccia M, Gallo E, Rambaldi A, Paoloni F, Fioritoni G, Ferrara F, Specchia G, Cimino G, Diverio D, Borlenghi E, Martinelli G, Di Raimondo F, Di Bona E, Fazi P, Peta A, Bosi A, Carella AM, Fabbiano F, Pogliani EM, Petti MC, Amadori S, Mandelli F; GIMEMA. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood. 2010 Oct 8;116(17):3171-9. Epub 2010 Jul 19. [http://www.bloodjournal.org/content/116/17/3171.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20644121 PubMed] NCT001064570
 
−
==Cytarabine & Idarubicin, then Mitoxantrone, then Cytarabine & Idarubicin, with ATRA {{#subobject:ca29a4|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:46f412|Variant=1}}===
+
===Protocol, Maintenance Cycles 1-6===
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/115/25/5137.long Sanz et al. 2010 (PETHEMA LPA2005)]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
''This is risk-adapted therapy for <u>high-risk younger than 60</u> patients in '''PETHEMA LPA2005'''. Note that it is unclear from the paper which route the cytarabine is given in the third consolidation; this dose can be given by IV or SC routes.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#ATRA_.26_Idarubicin|ATRA & idarubicin]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy, consolidation #1====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 15
 
−
====Chemotherapy, consolidation #1====
 
−
*[[Idarubicin (Idamycin)]] 5 mg/m<sup>2</sup> IV once per day on days 1 to 4
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 to 4
 
−
'''1-month course, followed by:'''
 
−
====Targeted therapy, consolidation #2====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 15
 
−
====Chemotherapy, consolidation #2====
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
'''1-month course, followed by:'''
 
−
====Targeted therapy, consolidation #3====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 15
 
−
====Chemotherapy, consolidation #3====
 
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cytarabine (Ara-C)]] 150 mg/m<sup>2</sup> IV or SC every 8 hours on days 1 to 4 (total dose: 1800 mg/m<sup>2</sup>)
 
−
'''1-month course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]] maintenance
 
−
</div></div>
 
−
===References===
 
−
# '''PETHEMA LPA2005:''' Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA; HOVON. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. Epub 2010 Apr 14. [http://www.bloodjournal.org/content/115/25/5137.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20393132 PubMed] NCT00408278
 
−
==Daunorubicin monotherapy {{#subobject:76a47b|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:82b9d5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.08.1596 Adès et al. 2006 (EAPLG APL 2000)]
 
−
|2000-2004
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#Cytarabine_.26_Daunorubicin|Cytarabine & Daunorubicin]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
''This consolidation arm was a randomization for younger (less than 60), low-risk (WBC count less than 10 x 10<sup>9</sup>/L) patients. Low-risk (WBC count less than 10 x 10<sup>9</sup>/L) older (greater than 60) patients received this regimen in a non-randomized fashion.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#ATRA_.26_Daunorubicin|ATRA & daunorubicin]] induction
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Daunorubicin (Cerubidine)]] as follows:
+
*[[Vinorelbine (Navelbine)]] by the following BSA-based criteria:
−
**Cycle 1: 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
+
**0.25-0.29 m<sup>2</sup> BSA: 4 mg IV push over 6 to 10 minutes on days 1, 8, and 15
−
**Cycle 2: 45 mg/m<sup>2</sup> IV once per day on days 1 to 3
+
**0.3-0.34 m<sup>2</sup> BSA: 6 mg IV push over 6 to 10 minutes on days 1, 8, and 15
−
</div>
+
**0.35-0.39 m<sup>2</sup> BSA: 7.5 mg IV push over 6 to 10 minutes on days 1, 8, and 15
−
<div class="toccolours" style="background-color:#cbd5e7">
+
**0.4-0.44 m<sup>2</sup> BSA: 9 mg IV push over 6 to 10 minutes on days 1, 8, and 15
−
====Subsequent treatment====
+
**0.45-0.49 m<sup>2</sup> BSA: 11 mg IV push over 6 to 10 minutes on days 1, 8, and 15
−
*[[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]] maintenance
+
**0.5-0.54 m<sup>2</sup> BSA: 12 mg IV push over 6 to 10 minutes on days 1, 8, and 15
 +
**0.55-0.59 m<sup>2</sup> BSA: 14 mg IV push over 6 to 10 minutes on days 1, 8, and 15
 +
**≥ 0.6 m<sup>2</sup> BSA: 25 mg/m<sup>2</sup> IV push over 6 to 10 minutes on days 1, 8, and 15
 +
*[[Cyclophosphamide (Cytoxan)]] 25 mg/m<sup>2</sup> PO once daily on days 1 through 28
 +
**Dose rounded to the nearest 25 mg capsule
 +
'''28-day cycle'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''EAPLG APL 2000:''' Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; EAPLG. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. [https://doi.org/10.1200/jco.2006.08.1596 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17116939 PubMed] NCT00591526
+
# '''Vinorelbine and low dose cyclophosphamide maintenance therapy:''' Vinorelbine and low dose cyclophosphamide maintenance therapy: Bisogno G, De Salvo GL, Bergeron C, Gallego Melcons s, Merks JH, Kelsey A, Martelli H, Minard-Colin V, Orbach D, Glosli H, Chisholm J, Casanova M, Zanetti I, Devalck C, Ben-Arush M, Mudry P, Ferman S, Jenney M, Ferrari A. Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 tial. Lancet Oncol. 2019 Nov;20(11):1566-1575. [https://doi.org/10.1016/S1470-2045(19)30617-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31562043/ PubMed]  
−
## '''Pooled subgroup analysis:''' Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://www.bloodjournal.org/content/111/3/1078.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17975017 PubMed]
+
# '''COG ARST1431:''' [https://clinicaltrials.gov/ct2/show/NCT02567435 NCT02567435]
−
==Idarubicin, then Mitoxantrone, then Idarubicin {{#subobject:6af14e|Regimen=1}}==
+
==COG ARST0531 VAC Arm==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:11923f|Variant=1}}===
+
===Protocol, Weeks 1-15===
−
{| class="wikitable" style="width: 40%; text-align:center;"
+
====Chemotherapy, Week 1====
−
!style="width: 25%"|Study
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|-
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|[http://www.bloodjournal.org/content/103/4/1237.full Sanz et al. 2003 (PETHEMA LPA96)]
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
| style="background-color:#91cf61" |Non-randomized
+
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
−
|-
+
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
−
|[http://www.bloodjournal.org/content/103/4/1237.full Sanz et al. 2003 (PETHEMA LPA99)]
+
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
−
| style="background-color:#91cf61" |Non-randomized
+
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
−
|-
+
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
−
|}
+
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
−
''This was the <u>low-risk</u> treatment arm of '''PETHEMA LPA99'''; <u>all patients</u> on '''PETHEMA LPA96''' underwent this consolidation protocol.''
+
====Supportive Medications, Week 1====
−
<div class="toccolours" style="background-color:#cbd5e8">
+
*[[Mesna (Mesnex)]] by the following age-based criteria:
−
====Preceding treatment====
+
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
*[[#ATRA_.26_Idarubicin|ATRA & idarubicin]] induction
+
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
</div>
+
====Chemotherapy, Week 2====
−
<div class="toccolours" style="background-color:#b3e2cd">
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
====Chemotherapy, part 1====
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[Idarubicin (Idamycin)]] 5 mg/m<sup>2</sup> IV once per day on days 1 to 4
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
'''1-month cycle, followed by:'''
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
====Chemotherapy, part 2====
+
====Chemotherapy, Week 3====
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once per day on days 1 to 5
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
'''1-month cycle, followed by:'''
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
====Chemotherapy, part 3====
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once on day 1
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
'''1-month cycle'''
+
====Chemotherapy, Week 4====
−
</div>
+
*Radiation therapy begins
−
<div class="toccolours" style="background-color:#cbd5e7">
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
====Subsequent treatment====
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]] maintenance
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
</div></div>
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
===References===
+
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
−
# '''PETHEMA LPA96:''' Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. [http://www.bloodjournal.org/content/103/4/1237.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14576047 PubMed]
+
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
−
## '''Pooled subgroup analysis:''' Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://www.bloodjournal.org/content/111/3/1078.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17975017 PubMed]
+
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
−
# '''PETHEMA LPA99:''' Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. [http://www.bloodjournal.org/content/103/4/1237.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14576047 PubMed] NCT00465933
+
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
−
## '''Pooled subgroup analysis:''' Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://www.bloodjournal.org/content/111/3/1078.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17975017 PubMed]
+
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
−
==Idarubicin, then Mitoxantrone, then Idarubicin, with ATRA {{#subobject:49fc49|Regimen=1}}==
+
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 4====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 5====
 +
*Radiation therapy continues
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 6====
 +
*Radiation therapy continues
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 7====
 +
*Radiation therapy continues
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 7====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 8====
 +
*Radiation therapy continues
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 9====
 +
*Radiation therapy final week
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 10====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 10====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 11====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 12====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 13====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 13====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 14 Off Chemo====
 +
====Chemotherapy, Week 15 Evaluation====
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol variant #1 {{#subobject:8d3f07|Variant=1}}===
+
===Protocol, Weeks 16-30===
−
{| class="wikitable" style="width: 40%; text-align:center;"
+
====Chemotherapy, Week 16====
−
!style="width: 25%"|Study
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|-
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|[http://www.bloodjournal.org/content/116/17/3171.long Lo-Coco et al. 2010 (GIMEMA AIDA-2000)]
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
| style="background-color:#91cf61" |Non-randomized
+
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
−
|-
+
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
−
|[http://www.bloodjournal.org/content/115/25/5137.long Sanz et al. 2010 (PETHEMA LPA2005)]
+
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
−
| style="background-color:#91cf61" |Non-randomized
+
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
−
|-
+
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
−
|[https://doi.org/10.1056/NEJMoa1300874 Lo-Coco et al. 2013 (GIMEMA/DSIL APL0406)]
+
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
+
====Supportive Medications, Week 16====
−
|-
+
*[[Mesna (Mesnex)]] by the following age-based criteria:
−
|}
+
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
''This is risk-adapted therapy for <u>intermediate- and low-risk</u> patients in '''AIDA-2000''' and for <u>low-risk</u> patients in '''PETHEMA LPA2005'''; all patients assigned to the chemotherapy arm of '''GIMEMA/DSIL APL0406''' received this treatment. Note that the number of mitoxantrone doses differs between the protocols.''
+
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
<div class="toccolours" style="background-color:#cbd5e8">
+
====Chemotherapy, Week 17 Off Chemo====
−
====Preceding treatment====
+
====Chemotherapy, Week 18 Off Chemo====
−
*[[#ATRA_.26_Idarubicin|ATRA & idarubicin]] induction
+
====Chemotherapy, Week 19====
−
</div>
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
<div class="toccolours" style="background-color:#b3e2cd">
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
====Targeted therapy, part 1====
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m<sup>2</sup>/day PO for a total of 15 days
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
====Chemotherapy, part 1====
+
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
−
*[[Idarubicin (Idamycin)]] 5 mg/m<sup>2</sup> IV once per day on days 1 to 4
+
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
−
'''1-month course, followed by:'''
+
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
−
====Targeted therapy, part 2====
+
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m<sup>2</sup>/day PO for a total of 15 days
+
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
−
====Chemotherapy, part 2====
+
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
−
*[[Mitoxantrone (Novantrone)]] by the following study-specific criteria:
+
====Supportive Medications, Week 19====
−
**AIDA-2000 & GIMEMA/DSIL APL0406: 10 mg/m<sup>2</sup> IV once per day on days 1 to 5
+
*[[Mesna (Mesnex)]] by the following age-based criteria:
−
**PETHEMA LPA2005: 10 mg/m<sup>2</sup> IV once per day on days 1 to 3
+
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
'''1-month course, followed by:'''
+
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
====Targeted therapy, part 3====
+
====Chemotherapy, Week 20====
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m<sup>2</sup>/day PO for a total of 15 days
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
====Chemotherapy, part 3====
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once on day 1
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
'''1-month course'''
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
</div>
+
====Chemotherapy, Week 21====
−
<div class="toccolours" style="background-color:#cbd5e7">
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
====Subsequent treatment====
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*AIDA-2000 and GIMEMA/DSIL APL0406: [[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA alternating with 6-MP, MTX]] maintenance
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*PETHEMA LPA2005: [[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]] maintenance
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
</div></div><br>
+
====Chemotherapy, Week 22====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 22====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 23====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 24====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 25====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 25====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 26 Off Chemo====
 +
====Chemotherapy, Week 27 Off Chemo====
 +
====Chemotherapy, Week 28====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 28====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 29 Off Chemo====
 +
====Chemotherapy, Week 30 Evaluation====
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol variant #2 {{#subobject:6744ce|Variant=1}}===
+
===Protocol, Weeks 31-43===
−
{| class="wikitable" style="width: 40%; text-align:center;"
+
====Chemotherapy, Week 31====
−
!style="width: 25%"|Study
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|-
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|[http://www.bloodjournal.org/content/103/4/1237.full Sanz et al. 2003 (PETHEMA LPA99)]
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
| style="background-color:#91cf61" |Non-randomized
+
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
−
|-
+
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
−
|[http://www.bloodjournal.org/content/115/25/5137.long Sanz et al. 2010 (PETHEMA LPA2005)]
+
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
−
| style="background-color:#91cf61" |Non-randomized
+
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
−
|-
+
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
−
|}
+
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
−
''This is risk-adapted therapy for <u>intermediate-</u> and <u>high-risk</u> patients in PETHEMA LPA99 and for <u>intermediate-risk</u> and <u>high-risk older than 60</u> patients in PETHEMA LPA2005. Note that the number of mitoxantrone doses differs between the two protocols.''
+
====Supportive Medications, Week 31====
−
<div class="toccolours" style="background-color:#cbd5e8">
+
*[[Mesna (Mesnex)]] by the following age-based criteria:
−
====Preceding treatment====
+
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
*[[#ATRA_.26_Idarubicin|ATRA & idarubicin]] induction
+
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
</div>
+
====Chemotherapy, Week 32====
−
<div class="toccolours" style="background-color:#b3e2cd">
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
====Targeted therapy, part 1====
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 15
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
====Chemotherapy, part 1====
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
*[[Idarubicin (Idamycin)]] 7 mg/m<sup>2</sup> IV once per day on days 1 to 4
+
====Chemotherapy, Week 33====
−
'''1-month course, followed by:'''
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
====Targeted therapy, part 2====
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 15
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
====Chemotherapy, part 2====
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
*[[Mitoxantrone (Novantrone)]] by the following study-specific criteria:
+
====Chemotherapy, Week 34====
−
**PETHEMA LPA99: 10 mg/m<sup>2</sup> IV once per day on days 1 to 5
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
**PETHEMA LPA2005: 10 mg/m<sup>2</sup> IV once per day on days 1 to 3
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
'''1-month course, followed by:'''
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
====Targeted therapy, part 3====
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 15
+
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
−
====Chemotherapy, part 3====
+
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
−
'''1-month course'''
+
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
−
</div>
+
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
−
<div class="toccolours" style="background-color:#cbd5e7">
+
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
−
====Subsequent treatment====
+
====Supportive Medications, Week 34====
−
*[[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]] maintenance
+
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 35====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 36====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 37====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 37====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 38 Off Chemo====
 +
====Chemotherapy, Week 39 Off Chemo====
 +
====Chemotherapy, Week 40====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 40====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 41 Off Chemo====
 +
====Chemotherapy, Week 42 Off Chemo====
 +
====Chemotherapy, Week 43 Evaluation====
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''PETHEMA LPA99:''' Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. [http://www.bloodjournal.org/content/103/4/1237.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14576047 PubMed] NCT00465933
+
# '''COG ARST0531:''' Hawkins DS, Chi Y, Anderson JR, Tian, J, Arndt CAS, Bomgaars L, Donaldson SS, Hayes-Jordan A, Mascarenhas L, McCarville MB, McCune JS, McCowage G, Million L, Morris CD, Parham DM, Rodeberg DA, Rudzinski ER, Shnorhavorian M, Spunt SL, Skapek SX, Teot LA, Wolden S, Yock TI, Meyer WH. Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve OUtcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2018 Sep;36(27):2770-2777. [https://doi.org/10.1200/JCO.2018.77.9694 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30091945/ PubMed] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145831/ PMC Article] NCT01222715
−
## '''Pooled subgroup analysis:''' Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://www.bloodjournal.org/content/111/3/1078.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17975017 PubMed]
+
==COG ARST0531 VAC/VI Arm==
−
# '''PETHEMA LPA2005:''' Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA; HOVON. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. Epub 2010 Apr 14. [http://www.bloodjournal.org/content/115/25/5137.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20393132 PubMed] NCT00408278
 
−
# '''GIMEMA AIDA-2000:''' Lo-Coco F, Avvisati G, Vignetti M, Breccia M, Gallo E, Rambaldi A, Paoloni F, Fioritoni G, Ferrara F, Specchia G, Cimino G, Diverio D, Borlenghi E, Martinelli G, Di Raimondo F, Di Bona E, Fazi P, Peta A, Bosi A, Carella AM, Fabbiano F, Pogliani EM, Petti MC, Amadori S, Mandelli F; GIMEMA. Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group. Blood. 2010 Oct 8;116(17):3171-9. Epub 2010 Jul 19. [http://www.bloodjournal.org/content/116/17/3171.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20644121 PubMed] NCT001064570
 
−
# '''GIMEMA/DSIL APL0406:''' Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. [https://doi.org/10.1056/NEJMoa1300874 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23841729 PubMed] NCT00482833
 
−
## '''HRQoL analysis:''' Efficace F, Mandelli F, Avvisati G, Cottone F, Ferrara F, Di Bona E, Specchia G, Breccia M, Levis A, Sica S, Finizio O, Kropp MG, Fioritoni G, Cerqui E, Vignetti M, Amadori S, Schlenk RF, Platzbecker U, Lo-Coco F. Randomized phase III trial of retinoic acid and arsenic trioxide versus retinoic acid and chemotherapy in patients with acute promyelocytic leukemia: health-related quality-of-life outcomes. J Clin Oncol. 2014 Oct 20;32(30):3406-12. Epub 2014 Sep 22. [https://doi.org/10.1200/JCO.2014.55.3453 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25245446 PubMed]
 
−
## '''Update:''' Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute promyelocytic leukemia: final results of the randomized Italian-German APL0406 trial. J Clin Oncol. 2017 Feb 20;35(6):605-612. Epub 2016 Oct 31. [https://doi.org/10.1200/JCO.2016.67.1982 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27400939 PubMed]
 
−
## '''Update:''' Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts CH, Hanel M, Rollig C, Schmitz N, Link H, Frairia C, Fozza C, Maria D'Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Voso MT, Ehninger G, Schlenk RF, Lo-Coco F. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial. Leukemia. 2020 Mar;34(3):914-918. Epub 2019 Oct 14. [https://doi.org/10.1038/s41375-019-0589-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31611624 PubMed]
 
−
=Maintenance after upfront therapy=
 
−
==Arsenic trioxide monotherapy {{#subobject:e1f355|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 0.15 mg/kg (pediatric dosing) {{#subobject:9f326b|Variant=1}}===
+
===Protocol, Weeks 1-15===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
+
====Chemotherapy, Week 1====
−
!style="width: 33%"|Study
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
!style="width: 33%"|Years of enrollment
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|-
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
|[https://doi.org/10.1182/blood-2005-08-3532 Mathews et al. 2006]
+
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
−
|1998-2004
+
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
−
| style="background-color:#91cf61" |Non-randomized
+
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
−
|-
+
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
−
|}
+
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
−
<div class="toccolours" style="background-color:#cbd5e8">
+
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
−
====Preceding treatment====
+
====Supportive Medications, Week 1====
−
*[[#Arsenic_trioxide_monotherapy_2|Arsenic trioxide]] consolidation
+
*[[Mesna (Mesnex)]] by the following age-based criteria:
−
</div>
+
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
<div class="toccolours" style="background-color:#b3e2cd">
+
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
====Targeted therapy====
+
====Chemotherapy, Week 2====
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV over 2 to 3 hours once per day on days 1 to 10
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
'''Monthly cycle for 6 cycles'''
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
</div></div><br>
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
<div class="toccolours" style="background-color:#eeeeee">
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
===Regimen variant #2, 10 mg (flat dose) {{#subobject:9f486b|Variant=1}}===
+
====Chemotherapy, Week 3====
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
!style="width: 33%"|Study
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
!style="width: 33%"|Years of enrollment
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
|-
+
====Chemotherapy, Week 4====
−
|[https://doi.org/10.1182/blood-2005-08-3532 Mathews et al. 2006]
+
*Radiation therapy begins
−
|1998-2004
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
| style="background-color:#91cf61" |Non-randomized
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|-
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|}
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
<div class="toccolours" style="background-color:#cbd5e8">
+
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
−
====Preceding treatment====
+
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5
−
*[[#Arsenic_trioxide_monotherapy_2|Arsenic trioxide]] consolidation
+
====Chemotherapy, Week 5====
−
</div>
+
*Radiation therapy continues
−
<div class="toccolours" style="background-color:#b3e2cd">
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
====Targeted therapy====
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[Arsenic trioxide (Trisenox)]] 10 mg IV over 2 to 3 hours once per day on days 1 to 10
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
'''Monthly cycle for 6 cycles'''
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
</div></div>
+
====Chemotherapy, Week 6====
−
===References===
+
*Radiation therapy continues
−
# Mathews V, George B, Lakshmi KM, Viswabandya A, Bajel A, Balasubramanian P, Shaji RV, Srivastava VM, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006 Apr 1;107(7):2627-32. Epub 2005 Dec 13. [https://doi.org/10.1182/blood-2005-08-3532 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16352810 PubMed]
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
## '''Update:''' Mathews V, George B, Chendamarai E, Lakshmi KM, Desire S, Balasubramanian P, Viswabandya A, Thirugnanam R, Abraham A, Shaji RV, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol. 2010 Aug 20;28(24):3866-71. Epub 2010 Jul 19. [https://doi.org/10.1200/jco.2010.28.5031 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20644086 PubMed]
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
==ATRA monotherapy {{#subobject:8c70f0|Regimen=1}}==
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 7====
 +
*Radiation therapy continues
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
 +
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5
 +
====Chemotherapy, Week 8====
 +
*Radiation therapy continues
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 9====
 +
*Radiation therapy final week
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 10====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 10====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 11====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 12====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 13====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 13====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 14 Off Chemo====
 +
====Chemotherapy, Week 15 Evaluation====
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1 {{#subobject:f68d7e|Variant=1}}===
+
===Protocol, Weeks 16-30===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
+
====Chemotherapy, Week 16====
−
!style="width: 20%"|Study
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
!style="width: 20%"|Years of enrollment
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
!style="width: 20%"|Comparator
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
−
|-
+
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ Powell et al. 2010 (C9710)]
+
====Chemotherapy, Week 17====
−
|1999-2005
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|[[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]]
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
| style="background-color:#fee08b" |Might have inferior DFS
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
|-
+
====Chemotherapy, Week 18 Off Chemo====
−
|}
+
====Chemotherapy, Week 19====
−
''Maintenance therapy starts 2 to 4 weeks after recovery from consolidation therapy.''
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
<div class="toccolours" style="background-color:#cbd5e8">
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
====Preceding treatment====
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[#Arsenic_trioxide.2C_then_ATRA_.26_Daunorubicin|Arsenic trioxide, then ATRA & daunorubicin]] consolidation versus [[#ATRA_.26_Daunorubicin|ATRA & daunorubicin]] consolidation
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
</div>
+
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
−
<div class="toccolours" style="background-color:#b3e2cd">
+
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5
−
====Targeted therapy====
+
====Chemotherapy, Week 20====
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 7
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
'''14-day cycle for 26 cycles (1 year)'''
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
</div></div><br>
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 21 Off Chemo====
 +
====Chemotherapy, Week 22====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 22====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 23====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 24====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 25====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
 +
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5
 +
====Chemotherapy, Week 26====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 27 Off Chemo====
 +
====Chemotherapy, Week 28====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 28====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 29 Off Chemo====
 +
====Chemotherapy, Week 30 Evaluation====
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2 {{#subobject:dc527a|Variant=1}}===
+
===Protocol, Weeks 31-43===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
+
====Chemotherapy, Week 31====
−
!style="width: 20%"|Study
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
!style="width: 20%"|Years of enrollment
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
!style="width: 20%"|Comparator
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
−
|-
+
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5
−
| rowspan="3" |[http://www.bloodjournal.org/content/90/3/1014.long Mandelli et al. 1997 (GIMEMA AIDA 0493)]
+
====Chemotherapy, Week 32====
−
|rowspan=3|1993-1996
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|1. [[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]]
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of molecular DFS
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
|-
+
====Chemotherapy, Week 33====
−
|2. [[#Mercaptopurine_.26_Methotrexate|6-MP & MTX]]
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of molecular DFS
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|-
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|3. [[Acute_promyelocytic_leukemia_-_null_regimens#Observation|No further treatment]]
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of molecular DFS
+
====Chemotherapy, Week 34====
−
|-
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
| rowspan="2" |[http://www.bloodjournal.org/content/94/4/1192.long Fenaux et al. 1999 (EAPLG APL 93)]
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|rowspan=2|1993-1996
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
|1. [[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]]
+
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
−
| style="background-color:#d73027" |Inferior 2-year relapse rate
+
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
−
|-
+
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
−
|2. [[#Mercaptopurine_.26_Methotrexate|6-MP & MTX]]<br> 3. [[Acute_promyelocytic_leukemia_-_null_regimens#Observation|No further treatment]]
+
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
−
| style="background-color:#91cf60" |Seems to have superior 2-year relapse rate
+
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
−
|-
+
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
−
|}
+
====Supportive Medications, Week 34====
−
<div class="toccolours" style="background-color:#cbd5e8">
+
*[[Mesna (Mesnex)]] by the following age-based criteria:
−
====Preceding treatment====
+
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
*GIMEMA AIDA 0493: [[#Cytarabine_.26_Idarubicin.2C_then_Etoposide_.26_Mitoxantrone.2C_then_Cytarabine.2C_Idarubicin.2C_Thioguanine|Cytarabine & idarubicin, then etoposide & mitoxantrone, then cytarabine, idarubicin, thioguanine]] consolidation
+
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
*EAPLG APL 93: [[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin]] consolidation
+
====Chemotherapy, Week 35 Off Chemo====
−
</div>
+
====Chemotherapy, Week 36 Off Chemo====
−
<div class="toccolours" style="background-color:#b3e2cd">
+
====Chemotherapy, Week 37====
−
====Targeted therapy====
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m<sup>2</sup>/day PO on days 1 to 15
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
'''3-month cycle for 8 cycles (2 years)'''
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
 +
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5
 +
====Chemotherapy, Week 38====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 39 Off Chemo====
 +
====Chemotherapy, Week 40====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 41 Off Chemo====
 +
====Chemotherapy, Week 42 Off Chemo====
 +
====Chemotherapy, Week 43 Evaluation====
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''GIMEMA AIDA 0493:''' Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C, Broccia G, Cerri R, Falda M, Fioritoni G, Leoni F, Liso V, Petti MC, Rodeghiero F, Saglio G, Vegna ML, Visani G, Jehn U, Willemze R, Muus P, Pelicci PG, Biondi A, Lo Coco F; Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto; Associazione Italiana di Ematologia ed Oncologia Pediatrica. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Blood. 1997 Aug 1;90(3):1014-21. [http://www.bloodjournal.org/content/90/3/1014.long link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/9242531 PubMed]
+
# '''COG ARST0531:''' Hawkins DS, Chi Y, Anderson JR, Tian, J, Arndt CAS, Bomgaars L, Donaldson SS, Hayes-Jordan A, Mascarenhas L, McCarville MB, McCune JS, McCowage G, Million L, Morris CD, Parham DM, Rodeberg DA, Rudzinski ER, Shnorhavorian M, Spunt SL, Skapek SX, Teot LA, Wolden S, Yock TI, Meyer WH. Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve OUtcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2018 Sep;36(27):2770-2777. [https://doi.org/10.1200/JCO.2018.77.9694 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30091945/ PubMed] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145831/ PMC Article] NCT01222715
−
## '''Update:''' Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA; AIEOP; EORTC. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. [http://www.bloodjournal.org/content/117/18/4716.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21385856 PubMed]
+
=Low Risk=
−
# '''EAPLG APL 93:''' Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, Fey M, Rayon C, Huguet F, Sotto JJ, Gardin C, Makhoul PC, Travade P, Solary E, Fegueux N, Bordessoule D, Miguel JS, Link H, Desablens B, Stamatoullas A, Deconinck E, Maloisel F, Castaigne S, Preudhomme C, Degos L. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia; European APL Group. Blood. 1999 Aug 15;94(4):1192-200. [http://www.bloodjournal.org/content/94/4/1192.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/10438706 PubMed]
+
==COG ARST1431 Protocol C (VAC/VA Only)==
−
## '''Update:''' Adès L, Guerci A, Raffoux E, Sanz M, Chevallier P, Lapusan S, Recher C, Thomas X, Rayon C, Castaigne S, Tournilhac O, de Botton S, Ifrah N, Cahn JY, Solary E, Gardin C, Fegeux N, Bordessoule D, Ferrant A, Meyer-Monard S, Vey N, Dombret H, Degos L, Chevret S, Fenaux P; European APL Group. Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience. Blood. 2010 Mar 4;115(9):1690-6. Epub 2009 Dec 17. [http://www.bloodjournal.org/content/115/9/1690.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/20018913 PubMed]
 
−
# '''C9710:''' Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. [http://www.bloodjournal.org/content/116/19/3751.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20705755 PubMed] NCT00003934
 
−
==ATRA, Mercaptopurine, Methotrexate {{#subobject:b44ab6|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 45/50/15 {{#subobject:80d40a|Variant=1}}===
+
===Protocol, Cycles 1-4 (Weeks 1 through 12)===
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/4/1237.full Sanz et al. 2003 (PETHEMA LPA99)]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|[http://www.bloodjournal.org/content/115/25/5137.long Sanz et al. 2010 (PETHEMA LPA2005)]
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*PETHEMA LPA99, low-risk: [[#Idarubicin.2C_then_Mitoxantrone.2C_then_Idarubicin|Idarubicin, then Mitoxantrone, then Idarubicin]] consolidation
 
−
*PETHEMA LPA99, intermediate- and high-risk and PETHEMA LPA2005, low- and intermediate-risk: [[#Idarubicin.2C_then_Mitoxantrone.2C_then_Idarubicin.2C_with_ATRA|Idarubicin, then Mitoxantrone, then Idarubicin, with ATRA]] consolidation
 
−
*PETHEMA LPA2005, high-risk: [[#Cytarabine_.26_Idarubicin.2C_then_Mitoxantrone.2C_then_Cytarabine_.26_Idarubicin.2C_with_ATRA|Cytarabine & Idarubicin, then Mitoxantrone, then Cytarabine & Idarubicin, with ATRA]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 15
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Mercaptopurine (6-MP)]] 50 mg/m<sup>2</sup> PO once per day  
+
*[[Vincristine (Oncovin)]] by the following BSA-based criteria:
−
*[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> IM once per week
+
**0.25-0.29 m<sup>2</sup> BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
−
====Dose modifications====
+
**0.3-0.34 m<sup>2</sup> BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
−
*[[Methotrexate (MTX)]] and [[Mercaptopurine (6-MP)]] decreased by 50% if WBC count less than 3.5 × 10<sup>9</sup>/L
+
**0.35-0.39 m<sup>2</sup> BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
−
*[[Methotrexate (MTX)]] and [[Mercaptopurine (6-MP)]] stopped if WBC count less than 2.5 × 10<sup>9</sup>/L
+
**0.4-0.44 m<sup>2</sup> BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
−
'''90-day cycle for 8 cycles (2 years)'''
+
**0.45-0.49 m<sup>2</sup> BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
−
</div></div><br>
+
**0.5-0.54 m<sup>2</sup> BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
 +
**0.55-0.59 m<sup>2</sup> BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
 +
**≥ 0.6 m<sup>2</sup> BSA: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
 +
*[[Dactinomycin (Cosmegen)]] by the following weight-based criteria:
 +
**3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
 +
**4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
 +
**6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
 +
**7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
 +
**8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
 +
**10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
 +
**11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
 +
**12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
 +
**≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
 +
*[[Cyclophosphamide (Cytoxan)]] by the following BSA-based criteria:
 +
**0.25-0.29 m<sup>2</sup> BSA: 220 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
 +
**0.3-0.34 m<sup>2</sup> BSA: 280 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
 +
**0.35-0.39 m<sup>2</sup> BSA: 360 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
 +
**0.4-0.44 m<sup>2</sup> BSA: 440 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
 +
**0.45-0.49 m<sup>2</sup> BSA: 520 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
 +
**0.5-0.54 m<sup>2</sup> BSA: 600 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
 +
**0.55-0.59 m<sup>2</sup> BSA: 660 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
 +
**≥ 0.6 m<sup>2</sup> BSA: 1200 mg/m<sup>2</sup> IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
 +
====Supportive Medications====
 +
*[[Mesna (Mesnex)]] by the following BSA-based criteria:
 +
**0.25-0.29 m<sup>2</sup> BSA: 176 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.3-0.34 m<sup>2</sup> BSA: 224 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.35-0.39 m<sup>2</sup> BSA: 288 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.4-0.44 m<sup>2</sup> BSA: 352 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.45-0.49 m<sup>2</sup> BSA: 416 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.5-0.54 m<sup>2</sup> BSA: 480 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**0.55-0.59 m<sup>2</sup> BSA: 528 mg IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
**≥ 0.6 m<sup>2</sup> BSA: 960 mg/m<sup>2</sup> IV over 15 to 30 minutes immediately before [[Cyclophosphamide (Cytoxan)]] infusion, and again 4 and 8 hours after the start of [[Cyclophosphamide (Cytoxan)]] infusion
 +
***[[Mesna (Mesnex)]] can also be given PO at twice the IV dose
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol variant #2, 45/50/15, ATRA alternating with 6-MP, MTX {{#subobject:80d40a|Variant=1}}===
+
===Protocol, Cycles 5-8 (Weeks 13 through 24)===
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1300874 Lo-Coco et al. 2013 (GIMEMA/DSIL APL0406)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Idarubicin.2C_then_Mitoxantrone.2C_then_Idarubicin.2C_with_ATRA|Idarubicin, then Mitoxantrone, then Idarubicin, with ATRA]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, part 1====
 
−
*[[Mercaptopurine (6-MP)]] 50 mg/m<sup>2</sup> PO once per day
 
−
*[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> IM or PO once per week
 
−
'''3-month cycle for 4 cycles, alternating with part 2'''
 
−
====Targeted therapy, part 2====
 
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m<sup>2</sup>/day PO on days 1 to 15
 
−
'''3-month cycle for 4 cycles, alternating with part 1'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 45/60/20 {{#subobject:5c36f3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ Powell et al. 2010 (C9710)]
 
−
|1999-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#ATRA_monotherapy_2|ATRA]]
 
−
| style="background-color:#d9ef8b" |Might have superior DFS
 
−
|-
 
−
|}
 
−
''Maintenance therapy starts 2 to 4 weeks after recovery from consolidation therapy.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Arsenic_trioxide.2C_then_ATRA_.26_Daunorubicin|Arsenic trioxide, then ATRA & daunorubicin]] consolidation versus [[#ATRA_.26_Daunorubicin_2|ATRA & daunorubicin]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 7
 
−
====Chemotherapy====
 
−
*[[Mercaptopurine (6-MP)]] 60 mg/m<sup>2</sup> PO once per day
 
−
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once per day on days 1 & 8
 
−
'''14-day cycle for 26 cycles (1 year)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol variant #4, 45/90/15, ATRA alternating with 6-MP, MTX {{#subobject:1d7cb5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="3" |[http://www.bloodjournal.org/content/90/3/1014.long Mandelli et al. 1997 (GIMEMA AIDA 0493)]
 
−
|rowspan=3|1993-1996
 
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#ATRA_monotherapy_2|ATRA]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of molecular DFS
 
−
|-
 
−
|2. [[#Mercaptopurine_.26_Methotrexate|6-MP & MTX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of molecular DFS
 
−
|-
 
−
|3. [[Acute_promyelocytic_leukemia_-_null_regimens#Observation|No further treatment]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of molecular DFS
 
−
|-
 
−
| rowspan="2" |[http://www.bloodjournal.org/content/94/4/1192.long Fenaux et al. 1999 (EAPLG APL 93)]
 
−
|rowspan=2|1993-1996
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Mercaptopurine_.26_Methotrexate|6-MP & MTX]]
 
−
| style="background-color:#91cf60" |Seems to have superior 2-year relapse rate
 
−
|-
 
−
|2. [[#ATRA_monotherapy_2|ATRA]]<br> 3. [[Acute_promyelocytic_leukemia_-_null_regimens#Observation|No further treatment]]
 
−
| style="background-color:#1a9850" |Superior 2-year relapse rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*GIMEMA AIDA 0493: [[#Cytarabine_.26_Idarubicin.2C_then_Etoposide_.26_Mitoxantrone.2C_then_Cytarabine.2C_Idarubicin.2C_Thioguanine|Cytarabine & idarubicin, then etoposide & mitoxantrone, then cytarabine, idarubicin, thioguanine]] consolidation
 
−
*EAPLG APL 93: [[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, part 1====
 
−
*[[Mercaptopurine (6-MP)]] 90 mg/m<sup>2</sup> PO once per day
 
−
*[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> IM once per week
 
−
'''3-month cycle for 4 cycles, alternating with part 2'''
 
−
====Targeted therapy, part 2====
 
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m<sup>2</sup>/day PO on days 1 to 15
 
−
'''3-month cycle for 4 cycles, alternating with part 1'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, with range of 6-MP {{#subobject:85ef36|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.08.1596 Adès et al. 2006 (EAPLG APL 2000)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin]] consolidation versus [[#Daunorubicin_monotherapy|daunorubicin]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 15
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Mercaptopurine (6-MP)]] 50 to 90 mg/m<sup>2</sup> PO once per day  
+
*[[Vincristine (Oncovin)]] by the following BSA-based criteria:
−
*[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> PO once per week
+
**0.25-0.29 m<sup>2</sup> BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
−
'''90-day cycle for 8 cycles (2 years)'''
+
**0.3-0.34 m<sup>2</sup> BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
−
</div></div><br>
+
**0.35-0.39 m<sup>2</sup> BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
−
<div class="toccolours" style="background-color:#eeeeee">
+
**0.4-0.44 m<sup>2</sup> BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
−
===Regimen variant #6, with range of 6-MP & MTX {{#subobject:ac797|Variant=1}}===
+
**0.45-0.49 m<sup>2</sup> BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
+
**0.5-0.54 m<sup>2</sup> BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
−
!style="width: 33%"|Study
+
**0.55-0.59 m<sup>2</sup> BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
−
!style="width: 33%"|Years of enrollment
+
**≥ 0.6 m<sup>2</sup> BSA: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
*[[Dactinomycin (Cosmegen)]] by the following weight-based criteria:
−
|-
+
**3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
−
|[https://doi.org/10.1182/blood-2012-02-410746 Iland et al. 2012 (ALLG APML4)]
+
**4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
−
|2004-2009
+
**6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
−
| style="background-color:#91cf61" |Phase 2
+
**7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
−
|-
+
**8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
−
|}
+
**10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
−
''Maintenance starts 3 to 4 weeks after completion of consolidation cycle 2.''
+
**11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
−
<div class="toccolours" style="background-color:#cbd5e8">
+
**12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
−
====Preceding treatment====
+
**≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
−
*[[#Arsenic_trioxide_.26_ATRA_2|Arsenic trioxide & ATRA]] consolidation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[All-trans retinoic acid (ATRA)]] 22.5 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
====Chemotherapy====
 
−
*[[Mercaptopurine (6-MP)]] 50 to 90 mg/m<sup>2</sup> PO once per day on days 15 to 90
 
−
*[[Methotrexate (MTX)]] 5 to 15 mg/m<sup>2</sup>/week PO on days 15 to 90
 
−
====Dose modifications====
 
−
*[[Methotrexate (MTX)]] and [[Mercaptopurine (6-MP)]] doses titrated to ANC 1000 to 2000/uL and minimizing hepatotoxicity
 
−
'''90-day cycle for 8 cycles (2 years)'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''GIMEMA AIDA 0493:''' Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C, Broccia G, Cerri R, Falda M, Fioritoni G, Leoni F, Liso V, Petti MC, Rodeghiero F, Saglio G, Vegna ML, Visani G, Jehn U, Willemze R, Muus P, Pelicci PG, Biondi A, Lo Coco F; Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto; Associazione Italiana di Ematologia ed Oncologia Pediatrica. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Blood. 1997 Aug 1;90(3):1014-21. [http://www.bloodjournal.org/content/90/3/1014.long link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/9242531 PubMed]
+
# '''Vinorelbine and low dose cyclophosphamide maintenance therapy:''' Vinorelbine and low dose cyclophosphamide maintenance therapy: Bisogno G, De Salvo GL, Bergeron C, Gallego Melcons s, Merks JH, Kelsey A, Martelli H, Minard-Colin V, Orbach D, Glosli H, Chisholm J, Casanova M, Zanetti I, Devalck C, Ben-Arush M, Mudry P, Ferman S, Jenney M, Ferrari A. Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 tial. Lancet Oncol. 2019 Nov;20(11):1566-1575. [https://doi.org/10.1016/S1470-2045(19)30617-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31562043/ PubMed]  
−
## '''Update:''' Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA; AIEOP; EORTC. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. [http://www.bloodjournal.org/content/117/18/4716.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21385856 PubMed]
+
# '''COG ARST1431:''' [https://clinicaltrials.gov/ct2/show/NCT02567435 NCT02567435]
−
# '''EAPLG APL 93:''' Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, Fey M, Rayon C, Huguet F, Sotto JJ, Gardin C, Makhoul PC, Travade P, Solary E, Fegueux N, Bordessoule D, Miguel JS, Link H, Desablens B, Stamatoullas A, Deconinck E, Maloisel F, Castaigne S, Preudhomme C, Degos L. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia; European APL Group. Blood. 1999 Aug 15;94(4):1192-200. [http://www.bloodjournal.org/content/94/4/1192.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/10438706 PubMed]
+
==COG ARST0331 (In Process)==
−
## '''Update:''' Adès L, Guerci A, Raffoux E, Sanz M, Chevallier P, Lapusan S, Recher C, Thomas X, Rayon C, Castaigne S, Tournilhac O, de Botton S, Ifrah N, Cahn JY, Solary E, Gardin C, Fegeux N, Bordessoule D, Ferrant A, Meyer-Monard S, Vey N, Dombret H, Degos L, Chevret S, Fenaux P; European APL Group. Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience. Blood. 2010 Mar 4;115(9):1690-6. Epub 2009 Dec 17. [http://www.bloodjournal.org/content/115/9/1690.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/20018913 PubMed]
+
=High Risk=
−
# '''PETHEMA LPA99:''' Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. [http://www.bloodjournal.org/content/103/4/1237.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14576047 PubMed] NCT00465933
+
==COG ARST0431==
−
## '''Pooled subgroup analysis:''' Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://www.bloodjournal.org/content/111/3/1078.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17975017 PubMed]
 
−
# '''EAPLG APL 2000:''' Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; EAPLG. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. [https://doi.org/10.1200/jco.2006.08.1596 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17116939 PubMed] NCT00591526
 
−
## '''Pooled subgroup analysis:''' Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. [http://www.bloodjournal.org/content/111/3/1078.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17975017 PubMed]
 
−
# '''PETHEMA LPA2005:''' Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA; HOVON. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome. Blood. 2010 Jun 24;115(25):5137-46. Epub 2010 Apr 14. [http://www.bloodjournal.org/content/115/25/5137.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/20393132 PubMed] NCT00408278
 
−
# '''C9710:''' Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. [http://www.bloodjournal.org/content/116/19/3751.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981533/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20705755 PubMed] NCT00003934
 
−
# '''ALLG APML4:''' Iland HJ, Bradstock K, Supple SG, Catalano A, Collins M, Hertzberg M, Browett P, Grigg A, Firkin F, Hugman A, Reynolds J, Di Iulio J, Tiley C, Taylor K, Filshie R, Seldon M, Taper J, Szer J, Moore J, Bashford J, Seymour JF; Australasian Leukaemia and Lymphoma Group. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood. 2012 Aug 23;120(8):1570-80. Epub 2012 Jun 19. [https://doi.org/10.1182/blood-2012-02-410746 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22715121 PubMed] ACTRN12605000070639
 
−
# '''GIMEMA/DSIL APL0406:''' Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lübbert M, Hänel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Döhner K, Sauer M, Ganser A, Amadori S, Mandelli F, Döhner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. [https://doi.org/10.1056/NEJMoa1300874 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23841729 PubMed] NCT00482833
 
−
## '''HRQoL analysis:''' Efficace F, Mandelli F, Avvisati G, Cottone F, Ferrara F, Di Bona E, Specchia G, Breccia M, Levis A, Sica S, Finizio O, Kropp MG, Fioritoni G, Cerqui E, Vignetti M, Amadori S, Schlenk RF, Platzbecker U, Lo-Coco F. Randomized phase III trial of retinoic acid and arsenic trioxide versus retinoic acid and chemotherapy in patients with acute promyelocytic leukemia: health-related quality-of-life outcomes. J Clin Oncol. 2014 Oct 20;32(30):3406-12. Epub 2014 Sep 22. [https://doi.org/10.1200/JCO.2014.55.3453 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25245446 PubMed]
 
−
## '''Update:''' Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lübbert M, Brandts CH, Hänel M, Röllig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Döhner K, Ganser A, Döhner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F. Improved outcomes with retinoic acid and arsenic trioxide compared with retinoic acid and chemotherapy in non-high-risk acute promyelocytic leukemia: final results of the randomized Italian-German APL0406 trial. J Clin Oncol. 2017 Feb 20;35(6):605-612. Epub 2016 Oct 31. [https://doi.org/10.1200/JCO.2016.67.1982 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27400939 PubMed]
 
−
## '''Update:''' Cicconi L, Platzbecker U, Avvisati G, Paoloni F, Thiede C, Vignetti M, Fazi P, Ferrara F, Divona M, Albano F, Efficace F, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Annibali O, Wattad M, Lubbert M, Brandts CH, Hanel M, Rollig C, Schmitz N, Link H, Frairia C, Fozza C, Maria D'Arco A, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Voso MT, Ehninger G, Schlenk RF, Lo-Coco F. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian-German randomized trial. Leukemia. 2020 Mar;34(3):914-918. Epub 2019 Oct 14. [https://doi.org/10.1038/s41375-019-0589-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31611624 PubMed]
 
−
==Mercaptopurine & Methotrexate {{#subobject:a29183|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1 {{#subobject:ce7c69|Variant=1}}===
+
===Protocol, Weeks 1-6===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
+
====Chemotherapy, Week 1 (IRIN-VCR)====
−
!style="width: 20%"|Study
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
!style="width: 20%"|Years of enrollment
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
!style="width: 20%"|Comparator
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
−
|-
+
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5
−
|[http://www.bloodjournal.org/content/100/9/3141.long Avvisati et al. 2002 (GIMEMA LAP 0389)]
+
====Chemotherapy, Week 2 (VCR)====
−
|1989-1993
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
| style="background-color:#1a9851" |Phase 3 (C)
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|[[Acute_promyelocytic_leukemia_-_null_regimens#Observation|No further treatment]]
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
|-
+
====Chemotherapy, Week 3 (VCR)====
−
|}
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
<div class="toccolours" style="background-color:#cbd5e8">
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
====Preceding treatment====
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[#Cytarabine_.26_Idarubicin.2C_then_Etoposide_.26_Mitoxantrone.2C_then_Cytarabine.2C_Idarubicin.2C_Thioguanine|Cytarabine & idarubicin, then etoposide & mitoxantrone, then cytarabine, idarubicin, thioguanine]] consolidation
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
</div>
+
====Chemotherapy, Week 4 (IRIN-VCR)====
−
<div class="toccolours" style="background-color:#b3e2cd">
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
====Chemotherapy====
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[Mercaptopurine (6-MP)]] 1 mg/kg PO once per day  
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[Methotrexate (MTX)]] 0.25 mg/kg IM once per week
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
'''2-year course'''
+
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
−
</div></div><br>
+
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5
 +
====Chemotherapy, Week 5 (VCR)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 6 Evaluation====
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2 {{#subobject:bab868|Variant=1}}===
+
===Protocol, Weeks 7-19===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
+
====Chemotherapy, Week 7 (VDC)====
−
!style="width: 20%"|Study
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
!style="width: 20%"|Years of enrollment
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
!style="width: 20%"|Comparator
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
*[[Doxorubicin (Adriamycin)]] by the following age-based criteria:
−
|-
+
**Age ≥ 1 year: 37.5 mg/m<sup>2</sup> (Total dose per week of 75 mg/m<sup>2</sup>) IV over 24 hours once per day on days 1 through 2
−
| rowspan="3" |[http://www.bloodjournal.org/content/90/3/1014.long Mandelli et al. 1997 (GIMEMA AIDA 0493)]
+
**Age < 1 year: 18.75 mg/m<sup>2</sup> IV over 24 hours once per day on days 1 through 2
−
|rowspan=3|1993-1996
+
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (C)
+
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
−
|1. [[#ATRA_monotherapy_2|ATRA]]
+
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of molecular DFS
+
====Supportive Medications, Week 7====
−
|-
+
*[[Mesna (Mesnex)]] by the following age-based criteria:
−
|2. [[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]]
+
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of molecular DFS
+
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
|-
+
====Chemotherapy, Week 8 (VCR)====
−
|3. [[Acute_promyelocytic_leukemia_-_null_regimens#Observation|No further treatment]]
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of molecular DFS
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|-
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
| rowspan="2" |[http://www.bloodjournal.org/content/94/4/1192.long Fenaux et al. 1999 (EAPLG APL 93)]
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
|rowspan=2|1993-1996
+
====Chemotherapy, Week 9 (IE)====
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+
*[[Ifosfamide (Ifex)]] by the following age-based criteria:
−
|1. [[#ATRA_monotherapy_2|ATRA]]<br>2. [[#ATRA.2C_Mercaptopurine.2C_Methotrexate|ATRA, 6-MP, MTX]]
+
**Age ≥ 1 year: 1800 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 through 5
−
| style="background-color:#fc8d59" |Seems to have inferior 2-year relapse rate
+
**Age < 1 year: 900 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 through 5
−
|-
+
*[[Etoposide (Vepesid)]] by the following age-based criteria:
−
|3. [[Acute_promyelocytic_leukemia_-_null_regimens#Observation|No further treatment]]
+
**Age ≥ 1 year: 100 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 through 5
−
| style="background-color:#1a9850" |Superior 2-year relapse rate
+
**Age < 1 year: 50 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 through 5
−
|-
+
====Supportive Medications, Week 9====
−
|}
+
*[[Mesna (Mesnex)]] by the following age-based criteria:
−
''Note that this arm was dropped from AIDA 0493 from February 1997.''
+
**Age ≥ 3 years: 360 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Ifosfamide (Ifex)]] infusion on days 1 through 5
−
<div class="toccolours" style="background-color:#cbd5e8">
+
**Age < 3 years: 180 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Ifosfamide (Ifex)]] infusion on days 1 through 5
−
====Preceding treatment====
+
====Chemotherapy, Week 10 Off Chemo====
−
*GIMEMA AIDA 0493: [[#Cytarabine_.26_Idarubicin.2C_then_Etoposide_.26_Mitoxantrone.2C_then_Cytarabine.2C_Idarubicin.2C_Thioguanine|Cytarabine & idarubicin, then etoposide & mitoxantrone, then cytarabine, idarubicin, thioguanine]] consolidation
+
====Chemotherapy, Week 11 (VDC)====
−
*EAPLG APL 93: [[#Cytarabine_.26_Daunorubicin|Cytarabine & daunorubicin]] consolidation
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
</div>
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
<div class="toccolours" style="background-color:#b3e2cd">
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
====Chemotherapy====
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
*[[Mercaptopurine (6-MP)]] 90 mg/m<sup>2</sup> PO once per day  
+
*[[Doxorubicin (Adriamycin)]] by the following age-based criteria:
−
*[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> IM once per week
+
**Age ≥ 1 year: 37.5 mg/m<sup>2</sup> (Total dose per week of 75 mg/m<sup>2</sup>) IV over 24 hours once per day on days 1 through 2
−
'''2-year course'''
+
**Age < 1 year: 18.75 mg/m<sup>2</sup> IV over 24 hours once per day on days 1 through 2
−
</div></div>
+
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
−
===References===
+
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
−
# '''GIMEMA AIDA 0493:''' Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C, Broccia G, Cerri R, Falda M, Fioritoni G, Leoni F, Liso V, Petti MC, Rodeghiero F, Saglio G, Vegna ML, Visani G, Jehn U, Willemze R, Muus P, Pelicci PG, Biondi A, Lo Coco F; Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto; Associazione Italiana di Ematologia ed Oncologia Pediatrica. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Blood. 1997 Aug 1;90(3):1014-21. [http://www.bloodjournal.org/content/90/3/1014.long link to original article] '''contains partial protocol''' [https://pubmed.ncbi.nlm.nih.gov/9242531 PubMed]
+
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
−
## '''Update:''' Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA; AIEOP; EORTC. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. [http://www.bloodjournal.org/content/117/18/4716.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21385856 PubMed]
+
====Supportive Medications, Week 11====
−
# '''EAPLG APL 93:''' Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, Fey M, Rayon C, Huguet F, Sotto JJ, Gardin C, Makhoul PC, Travade P, Solary E, Fegueux N, Bordessoule D, Miguel JS, Link H, Desablens B, Stamatoullas A, Deconinck E, Maloisel F, Castaigne S, Preudhomme C, Degos L. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia; European APL Group. Blood. 1999 Aug 15;94(4):1192-200. [http://www.bloodjournal.org/content/94/4/1192.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/10438706 PubMed]
+
*[[Mesna (Mesnex)]] by the following age-based criteria:
−
## '''Update:''' Adès L, Guerci A, Raffoux E, Sanz M, Chevallier P, Lapusan S, Recher C, Thomas X, Rayon C, Castaigne S, Tournilhac O, de Botton S, Ifrah N, Cahn JY, Solary E, Gardin C, Fegeux N, Bordessoule D, Ferrant A, Meyer-Monard S, Vey N, Dombret H, Degos L, Chevret S, Fenaux P; European APL Group. Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience. Blood. 2010 Mar 4;115(9):1690-6. Epub 2009 Dec 17. [http://www.bloodjournal.org/content/115/9/1690.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/20018913 PubMed]
+
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
# '''GIMEMA LAP 0389:''' Avvisati G, Petti MC, Lo-Coco F, Vegna ML, Amadori S, Baccarani M, Cantore N, Di Bona E, Ferrara F, Fioritoni G, Gallo E, Invernizzi R, Lazzarino M, Liso V, Mariani G, Ricciuti F, Selleri C, Sica S, Veneri D, Mandelli F; GIMEMA. Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up. Blood. 2002 Nov 1;100(9):3141-6. [http://www.bloodjournal.org/content/100/9/3141.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12384411 PubMed]
+
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
=Relapsed or refractory, salvage induction therapy=
+
====Chemotherapy, Week 12 (VCR)====
−
==Arsenic trioxide monotherapy {{#subobject:734f95|Regimen=1}}==
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 13 (IE)====
 +
*[[Ifosfamide (Ifex)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 1800 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 through 5
 +
**Age < 1 year: 900 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 through 5
 +
*[[Etoposide (Vepesid)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 100 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 through 5
 +
**Age < 1 year: 50 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 through 5
 +
====Supportive Medications, Week 13====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 360 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Ifosfamide (Ifex)]] infusion on days 1 through 5
 +
**Age < 3 years: 180 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Ifosfamide (Ifex)]] infusion on days 1 through 5
 +
====Chemotherapy, Week 14 Off Chemo====
 +
====Chemotherapy, Week 15 (VDC)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Doxorubicin (Adriamycin)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 37.5 mg/m<sup>2</sup> (Total dose per week of 75 mg/m<sup>2</sup>) IV over 24 hours once per day on days 1 through 2
 +
**Age < 1 year: 18.75 mg/m<sup>2</sup> IV over 24 hours once per day on days 1 through 2
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 15====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 16 (VCR)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 17 (IE)====
 +
*[[Ifosfamide (Ifex)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 1800 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 through 5
 +
**Age < 1 year: 900 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 through 5
 +
*[[Etoposide (Vepesid)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 100 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 through 5
 +
**Age < 1 year: 50 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 through 5
 +
====Supportive Medications, Week 17====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 360 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Ifosfamide (Ifex)]] infusion on days 1 through 5
 +
**Age < 3 years: 180 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Ifosfamide (Ifex)]] infusion on days 1 through 5
 +
====Chemotherapy, Week 18 Off Chemo====
 +
====Chemotherapy, Week 19 Evaluation====
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 0.15 mg/kg/day {{#subobject:ffaa29|Variant=1}}===
+
===Protocol, Weeks 20-34===
−
{| class="wikitable" style="width: 60%; text-align:center;"
+
====Chemotherapy, Week 20 (IRIN-VCR)====
−
!style="width: 33%"|Study
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
!style="width: 33%"|Years of enrollment
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|-
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
|[https://doi.org/10.1056/NEJM199811053391901 Soignet et al. 1998]
+
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
−
|NR
+
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5
−
| style="background-color:#ffffbe" |Non-randomized, <20 pts
+
====Chemotherapy, Week 21 (VCR)====
−
|-
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
|[https://doi.org/10.1200/JCO.2001.19.18.3852 Soignet et al. 2001 (PLRXAS01)]
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|1998-1999
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
| style="background-color:#91cf61" |Phase 2 (RT)
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
|-
+
====Chemotherapy, Week 22 (VCR)====
−
|}
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
<div class="toccolours" style="background-color:#b3e2cd">
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
====Targeted therapy====
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV over 2 hours once per day  
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
'''Continued until CR or up to 60 days'''
+
====Chemotherapy, Week 23 (IRIN-VCR)====
−
</div>
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
<div class="toccolours" style="background-color:#cbd5e7">
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
====Subsequent treatment====
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
*Confirmed CR: Arsenic trioxide consolidation and optional maintenance
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
</div></div><br>
+
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
 +
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5
 +
====Chemotherapy, Week 24 (VCR)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 25 Off Chemo====
 +
====Chemotherapy, Week 26 (IE)====
 +
*[[Ifosfamide (Ifex)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 1800 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 through 5
 +
**Age < 1 year: 900 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 through 5
 +
*[[Etoposide (Vepesid)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 100 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 through 5
 +
**Age < 1 year: 50 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 through 5
 +
====Supportive Medications, Week 26====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 360 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Ifosfamide (Ifex)]] infusion on days 1 through 5
 +
**Age < 3 years: 180 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Ifosfamide (Ifex)]] infusion on days 1 through 5
 +
====Chemotherapy, Week 27 Off Chemo====
 +
====Chemotherapy, Week 28 (VDC)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Doxorubicin (Adriamycin)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 37.5 mg/m<sup>2</sup> (Total dose per week of 75 mg/m<sup>2</sup>) IV over 24 hours once per day on days 1 through 2
 +
**Age < 1 year: 18.75 mg/m<sup>2</sup> IV over 24 hours once per day on days 1 through 2
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 28====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 29 (VCR)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 30 (IE)====
 +
*[[Ifosfamide (Ifex)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 1800 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 through 5
 +
**Age < 1 year: 900 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 through 5
 +
*[[Etoposide (Vepesid)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 100 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 through 5
 +
**Age < 1 year: 50 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 through 5
 +
====Supportive Medications, Week 30====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 360 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Ifosfamide (Ifex)]] infusion on days 1 through 5
 +
**Age < 3 years: 180 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Ifosfamide (Ifex)]] infusion on days 1 through 5
 +
====Chemotherapy, Week 31 Off Chemo====
 +
====Chemotherapy, Week 32 (VDC)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Doxorubicin (Adriamycin)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 37.5 mg/m<sup>2</sup> (Total dose per week of 75 mg/m<sup>2</sup>) IV over 24 hours once per day on days 1 through 2
 +
**Age < 1 year: 18.75 mg/m<sup>2</sup> IV over 24 hours once per day on days 1 through 2
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 32====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 33 (VCR)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 34 Evaluation====
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, 10 mg/day {{#subobject:e2687c|Variant=1}}===
+
===Protocol, Weeks 35-54===
−
{| class="wikitable" style="width: 40%; text-align:center;"
+
====Chemotherapy, Week 35 (VAC)====
−
!style="width: 25%"|Study
+
*[[Vincristine (Oncovin)]] by the following age-based criteria:
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|-
+
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
−
|[http://www.bloodjournal.org/content/89/9/3354.long Shen et al. 1997]
+
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
−
| style="background-color:#ffffbe" |Non-randomized, <20 pts
+
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
−
|-
+
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
−
|}
+
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
−
<div class="toccolours" style="background-color:#b3e2cd">
+
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
−
====Targeted therapy====
+
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
−
*[[Arsenic trioxide (Trisenox)]] 10 mg IV over 2 to 3 hours once per day  
+
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
−
'''Continued until CR'''
+
====Supportive Medications, Week 35====
−
</div>
+
*[[Mesna (Mesnex)]] by the following age-based criteria:
−
<div class="toccolours" style="background-color:#cbd5e7">
+
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
====Subsequent treatment====
+
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
−
*Patients in CR: proceed after 30 days to another 28-day course of arsenic trioxide
+
====Chemotherapy, Week 36 Off Chemo====
 +
====Chemotherapy, Week 37 Off Chemo====
 +
====Chemotherapy, Week 38 (VAC)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 38====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 39 Off Chemo====
 +
====Chemotherapy, Week 40 Off Chemo====
 +
====Chemotherapy, Week 41 (VAC)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 41====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 42 (VCR)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 43 (VCR)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 44 (VAC)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
*[[Dactinomycin (Cosmegen)]] by the following age-based criteria:
 +
**Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
 +
**Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
 +
*[[Cyclophosphamide (Cytoxan)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1200 mg/m<sup>2</sup> IV over 1 hour once per day on day 1
 +
**Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
 +
====Supportive Medications, Week 44====
 +
*[[Mesna (Mesnex)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 240 mg/m<sup>2</sup> at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
**Age < 3 years: 8 mg/kg at hour 0, 4, and 8 from the start of each [[Cyclophosphamide (Cytoxan)]] infusion on days 1
 +
====Chemotherapy, Week 45 Off Chemo====
 +
====Chemotherapy, Week 46 Off Chemo====
 +
====Chemotherapy, Week 47 (IRIN-VCR)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
 +
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5
 +
====Chemotherapy, Week 48 (VCR)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 49 Off Chemo====
 +
====Chemotherapy, Week 50 (IRIN-VCR)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
***Administer [[Vincristine (Oncovin)]] before [[Irinotecan (Camptosar)]]
 +
*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5
 +
====Chemotherapy, Week 51 (VCR)====
 +
*[[Vincristine (Oncovin)]] by the following age-based criteria:
 +
**Age ≥ 3 years: 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
 +
**Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
 +
====Chemotherapy, Week 52 Off Chemo====
 +
====Chemotherapy, Week 53 Off Chemo====
 +
====Chemotherapy, Week 54 Evaluation====
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ, Chen Y, Zhou L, Fang ZW, Wang YT, Ma J, Zhang P, Zhang TD, Chen SJ, Chen Z, Wang ZY. Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II Clinical efficacy and pharmacokinetics in relapsed patients. Blood. 1997 May 1;89(9):3354-60. [http://www.bloodjournal.org/content/89/9/3354.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/9129042 PubMed]
+
# '''COG ARST0431:''' Weigel BJ, Lyden E, Anderson JR, Meyer WH, Parham DM, Rodeberg DA, Michalski JM, Hawkins DS, Arndt CAS. 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. Journal of Clinical Oncology. 2016 Oct;34(2):117-122. [https://doi.org/10.1200/jco.2015.63.4048 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070550/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26503200/ PubMed] NCT00354744
−
# Soignet SL, Maslak P, Wang ZG, Jhanwar S, Calleja E, Dardashti LJ, Corso D, DeBlasio A, Gabrilove J, Scheinberg DA, Pandolfi PP, Warrell RP Jr. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med. 1998 Nov 5;339(19):1341-8. [https://doi.org/10.1056/NEJM199811053391901 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9801394 PubMed]
 
−
# '''PLRXAS01:''' Soignet SL, Frankel SR, Douer D, Tallman MS, Kantarjian H, Calleja E, Stone RM, Kalaycio M, Scheinberg DA, Steinherz P, Sievers EL, Coutré S, Dahlberg S, Ellison R, Warrell RP Jr. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. 2001 Sep 15;19(18):3852-60. [https://doi.org/10.1200/JCO.2001.19.18.3852 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11559723 PubMed]
 
−
==Arsenic trioxide & Idarubicin {{#subobject:90ec9f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4d76db|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/121/16/3095.long Yanada et al. 2013 (JALSG APL205R)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV over 2 hours once per day, starting on day 1 and continuing until hematologic complete remission or maximum of 60 days
 
−
====Chemotherapy====
 
−
*[[Idarubicin (Idamycin)]] 12 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 2 (Idarubicin was added under special conditions; see text for details)
 
−
====CNS therapy====
 
−
*''Given once after platelet recovery, consisting of:''
 
−
**[[Cytarabine (Ara-C)]] 40 mg IT, admixed with MTX & steroids
 
−
**[[Methotrexate (MTX)]] 15 mg IT, admixed with Ara-C & steroids
 
−
**ONE of the following corticosteroids:
 
−
***[[Prednisolone (Millipred)]] 10 mg IT, admixed with Ara-C & MTX
 
−
***[[Dexamethasone (Decadron)]] 4 mg IT, admixed with Ara-C & MTX
 
−
'''One course of up to 60 days'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Arsenic_trioxide_monotherapy_5|Arsenic trioxide]] consolidation
 
−
</div></div>
 
−
===References===
 
−
# '''JALSG APL205R:''' Yanada M, Tsuzuki M, Fujita H, Fujimaki K, Fujisawa S, Sunami K, Taniwaki M, Ohwada A, Tsuboi K, Maeda A, Takeshita A, Ohtake S, Miyazaki Y, Atsuta Y, Kobayashi Y, Naoe T, Emi N; Japan Adult Leukemia Study Group. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013 Apr 18;121(16):3095-102. Epub 2013 Feb 14. [http://www.bloodjournal.org/content/121/16/3095.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23412094 PubMed] UMIN C000000302
 
−
==Tamibarotene monotherapy {{#subobject:fbdb9f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5d009e|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770883/ Sanford et al. 2015 (STAR-1)]
 
−
| style="background-color:#ffffbe" |Phase 2, <20 pts
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Tamibarotene (Amnoid)]] 3 mg/m<sup>2</sup> PO twice per day
 
−
'''Up to 56-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients achieving CR: [[#Tamibarotene_monotherapy_77|Tamibarotene]] consolidation, if not proceeding to transplant
 
−
</div></div>
 
−
===References===
 
−
# '''STAR-1:''' Sanford D, Lo-Coco F, Sanz MA, Di Bona E, Coutre S, Altman JK, Wetzler M, Allen SL, Ravandi F, Kantarjian H, Cortes JE. Tamibarotene in patients with acute promyelocytic leukaemia relapsing after treatment with all-trans retinoic acid and arsenic trioxide. Br J Haematol. 2015 Nov;171(4):471-7. Epub 2015 Jul 24. [https://doi.org/10.1111/bjh.13607 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770883/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26205361 PubMed] NCT00520208
 
−
=Consolidation after salvage therapy=
 
−
==Arsenic trioxide monotherapy {{#subobject:5de745|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:36556f|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/121/16/3095.long Yanada et al. 2013 (JALSG APL205R)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: intrathecal therapy is given at the conclusion of each cycle (3 doses total, including re-induction)''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Arsenic_trioxide_.26_Idarubicin|Arsenic trioxide & Idarubicin re-induction]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV once per day on days 1 to 25
 
−
====CNS therapy====
 
−
*[[Cytarabine (Ara-C)]] 40 mg IT once at the conclusion of each cycle, admixed with MTX & steroids
 
−
*[[Methotrexate (MTX)]] 15 mg IT once at the conclusion of each cycle, admixed with Ara-C & steroids
 
−
*ONE of the following corticosteroids:
 
−
**[[Prednisolone (Millipred)]] 10 mg IT once at the conclusion of each cycle, admixed with Ara-C & MTX
 
−
**[[Dexamethasone (Decadron)]] 4 mg IT once at the conclusion of each cycle, admixed with Ara-C & MTX
 
−
'''2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Stem_cell_mobilization#Cytarabine_.26_G-CSF|HiDAC & G-CSF stem cell mobilization]], then [[#Busulfan_.26_Melphalan.2C_then_auto_HSCT|Bu/Mel with auto HSCT]]
 
−
</div></div>
 
−
===References===
 
−
# '''JALSG APL205R:''' Yanada M, Tsuzuki M, Fujita H, Fujimaki K, Fujisawa S, Sunami K, Taniwaki M, Ohwada A, Tsuboi K, Maeda A, Takeshita A, Ohtake S, Miyazaki Y, Atsuta Y, Kobayashi Y, Naoe T, Emi N; Japan Adult Leukemia Study Group. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013 Apr 18;121(16):3095-102. Epub 2013 Feb 14. [http://www.bloodjournal.org/content/121/16/3095.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23412094 PubMed] UMIN C000000302
 
−
==Busulfan & Melphalan, then auto HSCT {{#subobject:ceba5e|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:8c92e5|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/121/16/3095.long Yanada et al. 2013 (JALSG APL205R)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Stem_cell_mobilization#Cytarabine_.26_G-CSF|HiDAC & G-CSF stem cell mobilization]]
 
−
</div>
 
−
{{#lst:Autologous HSCT|c5fc8f}}
 
−
</div>
 
−
===References===
 
−
# '''JALSG APL205R:''' Yanada M, Tsuzuki M, Fujita H, Fujimaki K, Fujisawa S, Sunami K, Taniwaki M, Ohwada A, Tsuboi K, Maeda A, Takeshita A, Ohtake S, Miyazaki Y, Atsuta Y, Kobayashi Y, Naoe T, Emi N; Japan Adult Leukemia Study Group. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013 Apr 18;121(16):3095-102. Epub 2013 Feb 14. [http://www.bloodjournal.org/content/121/16/3095.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23412094 PubMed] UMIN C000000302
 
−
[[Category:Acute promyelocytic leukemia regimens]]
 
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:Acute leukemias]]
+
[[Category:Bone sarcomas]]
 +
[[Category:Pediatric solid tumors]]

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Intermediate Risk

COG ARST1431 Protocol A (VAC/VI Only)

Protocol, Cycles 1-4 (Weeks 1 through 12)

Chemotherapy

  • Vincristine (Oncovin) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • 0.3-0.34 m2 BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • 0.35-0.39 m2 BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • 0.4-0.44 m2 BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • 0.45-0.49 m2 BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • 0.5-0.54 m2 BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • 0.55-0.59 m2 BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • ≥ 0.6 m2 BSA: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • Dactinomycin (Cosmegen) by the following weight-based criteria:
    • 3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • ≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 220 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • 0.3-0.34 m2 BSA: 280 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • 0.35-0.39 m2 BSA: 360 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • 0.4-0.44 m2 BSA: 440 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • 0.45-0.49 m2 BSA: 520 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • 0.5-0.54 m2 BSA: 600 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • 0.55-0.59 m2 BSA: 660 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • ≥ 0.6 m2 BSA: 1200 mg/m2 IV over 60 minutes on day 1 of weeks 1 and 7
  • Irinotecan (Camptosar) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 8 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • 0.3-0.34 m2 BSA: 12 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • 0.35-0.39 m2 BSA: 15 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • 0.4-0.44 m2 BSA: 18 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • 0.45-0.49 m2 BSA: 22 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • 0.5-0.54 m2 BSA: 24 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • 0.55-0.59 m2 BSA: 28 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • ≥ 0.6 m2 BSA: 50 mg/m2 IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10

Supportive Medications

Protocol, Cycles 5-10 (Weeks 13 through 30)

Chemotherapy

  • Vincristine (Oncovin) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • 0.3-0.34 m2 BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • 0.35-0.39 m2 BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • 0.4-0.44 m2 BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • 0.45-0.49 m2 BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • 0.5-0.54 m2 BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • 0.55-0.59 m2 BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • ≥ 0.6 m2 BSA: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • Dactinomycin (Cosmegen) by the following weight-based criteria:
    • 3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • ≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
  • Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 220 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • 0.3-0.34 m2 BSA: 280 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • 0.35-0.39 m2 BSA: 360 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • 0.4-0.44 m2 BSA: 440 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • 0.45-0.49 m2 BSA: 520 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • 0.5-0.54 m2 BSA: 600 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • 0.55-0.59 m2 BSA: 660 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • ≥ 0.6 m2 BSA: 1200 mg/m2 IV over 60 minutes on day 1 of weeks 13, 22, 28
  • Irinotecan (Camptosar) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 8 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • 0.3-0.34 m2 BSA: 12 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • 0.35-0.39 m2 BSA: 15 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • 0.4-0.44 m2 BSA: 18 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • 0.45-0.49 m2 BSA: 22 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • 0.5-0.54 m2 BSA: 24 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • 0.55-0.59 m2 BSA: 28 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • ≥ 0.6 m2 BSA: 50 mg/m2 IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25

Supportive Medications

Protocol, Cycles 11-14 (Weeks 31 through 42)

Chemotherapy

  • Vincristine (Oncovin) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • 0.3-0.34 m2 BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • 0.35-0.39 m2 BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • 0.4-0.44 m2 BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • 0.45-0.49 m2 BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • 0.5-0.54 m2 BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • 0.55-0.59 m2 BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • ≥ 0.6 m2 BSA: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • Dactinomycin (Cosmegen) by the following weight-based criteria:
    • 3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • ≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 220 mg IV over 60 minutes on day 1 of weeks 34, 40
    • 0.3-0.34 m2 BSA: 280 mg IV over 60 minutes on day 1 of weeks 34, 40
    • 0.35-0.39 m2 BSA: 360 mg IV over 60 minutes on day 1 of weeks 34, 40
    • 0.4-0.44 m2 BSA: 440 mg IV over 60 minutes on day 1 of weeks 34, 40
    • 0.45-0.49 m2 BSA: 520 mg IV over 60 minutes on day 1 of weeks 34, 40
    • 0.5-0.54 m2 BSA: 600 mg IV over 60 minutes on day 1 of weeks 34, 40
    • 0.55-0.59 m2 BSA: 660 mg IV over 60 minutes on day 1 of weeks 34, 40
    • ≥ 0.6 m2 BSA: 1200 mg/m2 IV over 60 minutes on day 1 of weeks 34, 40
  • Irinotecan (Camptosar) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 8 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • 0.3-0.34 m2 BSA: 12 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • 0.35-0.39 m2 BSA: 15 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • 0.4-0.44 m2 BSA: 18 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • 0.45-0.49 m2 BSA: 22 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • 0.5-0.54 m2 BSA: 24 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • 0.55-0.59 m2 BSA: 28 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • ≥ 0.6 m2 BSA: 50 mg/m2 IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37

Supportive Medications

Protocol, Maintenance Cycles 1-6

Chemotherapy

  • Vinorelbine (Navelbine) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 4 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • 0.3-0.34 m2 BSA: 6 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • 0.35-0.39 m2 BSA: 7.5 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • 0.4-0.44 m2 BSA: 9 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • 0.45-0.49 m2 BSA: 11 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • 0.5-0.54 m2 BSA: 12 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • 0.55-0.59 m2 BSA: 14 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • ≥ 0.6 m2 BSA: 25 mg/m2 IV push over 6 to 10 minutes on days 1, 8, and 15
  • Cyclophosphamide (Cytoxan) 25 mg/m2 PO once daily on days 1 through 28
    • Dose rounded to the nearest 25 mg capsule

28-day cycle

References

  1. Vinorelbine and low dose cyclophosphamide maintenance therapy: Vinorelbine and low dose cyclophosphamide maintenance therapy: Bisogno G, De Salvo GL, Bergeron C, Gallego Melcons s, Merks JH, Kelsey A, Martelli H, Minard-Colin V, Orbach D, Glosli H, Chisholm J, Casanova M, Zanetti I, Devalck C, Ben-Arush M, Mudry P, Ferman S, Jenney M, Ferrari A. Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 tial. Lancet Oncol. 2019 Nov;20(11):1566-1575. link to original article PubMed
  2. COG ARST1431: NCT02567435

COG ARST1431 Protocol B (VAC/VI Plus TORI)

Protocol, Cycles 1-4 (Weeks 1 through 12)

Chemotherapy

  • Temsirolimus (Torisel) by the following weight-based criteria:
    • < 10 kg: 0.5 mg/kg IV over 30 to 60 minutes once weekly on day 1 of weeks 1 through 12
    • > 10 kg: 15 mg/m2 (maximum dose of 25 mg) IV on day 1 of weeks 1 through 12
  • Vincristine (Oncovin) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • 0.3-0.34 m2 BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • 0.35-0.39 m2 BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • 0.4-0.44 m2 BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • 0.45-0.49 m2 BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • 0.5-0.54 m2 BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • 0.55-0.59 m2 BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
    • ≥ 0.6 m2 BSA: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 12
  • Dactinomycin (Cosmegen) by the following weight-based criteria:
    • 3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • 12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
    • ≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1 and 7
  • Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 220 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • 0.3-0.34 m2 BSA: 280 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • 0.35-0.39 m2 BSA: 360 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • 0.4-0.44 m2 BSA: 440 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • 0.45-0.49 m2 BSA: 520 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • 0.5-0.54 m2 BSA: 600 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • 0.55-0.59 m2 BSA: 660 mg IV over 60 minutes on day 1 of weeks 1 and 7
    • ≥ 0.6 m2 BSA: 1200 mg/m2 IV over 60 minutes on day 1 of weeks 1 and 7
  • Irinotecan (Camptosar) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 8 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • 0.3-0.34 m2 BSA: 12 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • 0.35-0.39 m2 BSA: 15 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • 0.4-0.44 m2 BSA: 18 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • 0.45-0.49 m2 BSA: 22 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • 0.5-0.54 m2 BSA: 24 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • 0.55-0.59 m2 BSA: 28 mg IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10
    • ≥ 0.6 m2 BSA: 50 mg/m2 IV over 90 minutes once daily on days 1 through 5 of weeks 4 and 10

Supportive Medications

Mesna (Mesnex) can also be given PO at twice the IV dose

Protocol, Cycles 5-10 (Weeks 13 through 30)

Chemotherapy

  • Temsirolimus (Torisel) by the following weight-based criteria:
    • < 10 kg: 0.5 mg/kg IV over 30 to 60 minutes once weekly on day 1 of weeks 21 through 30
    • > 10 kg: 15 mg/m2 (maximum dose of 25 mg) IV on day 1 of weeks 21 through 30
  • Vincristine (Oncovin) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • 0.3-0.34 m2 BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • 0.35-0.39 m2 BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • 0.4-0.44 m2 BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • 0.45-0.49 m2 BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • 0.5-0.54 m2 BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • 0.55-0.59 m2 BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
    • ≥ 0.6 m2 BSA: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13, 16, 17, 19, 20, 22 through 26, 28
  • Dactinomycin (Cosmegen) by the following weight-based criteria:
    • 3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • 12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
    • ≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 22, 28
Give week 13 dose of Dactinomycin (Cosmegen) before beginning radiation therapy
  • Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 220 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • 0.3-0.34 m2 BSA: 280 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • 0.35-0.39 m2 BSA: 360 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • 0.4-0.44 m2 BSA: 440 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • 0.45-0.49 m2 BSA: 520 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • 0.5-0.54 m2 BSA: 600 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • 0.55-0.59 m2 BSA: 660 mg IV over 60 minutes on day 1 of weeks 13, 22, 28
    • ≥ 0.6 m2 BSA: 1200 mg/m2 IV over 60 minutes on day 1 of weeks 13, 22, 28
  • Irinotecan (Camptosar) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 8 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • 0.3-0.34 m2 BSA: 12 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • 0.35-0.39 m2 BSA: 15 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • 0.4-0.44 m2 BSA: 18 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • 0.45-0.49 m2 BSA: 22 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • 0.5-0.54 m2 BSA: 24 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • 0.55-0.59 m2 BSA: 28 mg IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25
    • ≥ 0.6 m2 BSA: 50 mg/m2 IV over 90 minutes once daily on days 1 through 5 of weeks 16, 19, 25

Supportive Medications

Mesna (Mesnex) can also be given PO at twice the IV dose

Protocol, Cycles 11-14 (Weeks 31 through 42)

Chemotherapy

  • Temsirolimus (Torisel) by the following weight-based criteria:
    • < 10 kg: 0.5 mg/kg IV over 30 to 60 minutes once weekly on day 1 of weeks 31 through 42
    • > 10 kg: 15 mg/m2 (maximum dose of 25 mg) IV on day 1 of weeks 31 through 42
  • Vincristine (Oncovin) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • 0.3-0.34 m2 BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • 0.35-0.39 m2 BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • 0.4-0.44 m2 BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • 0.45-0.49 m2 BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • 0.5-0.54 m2 BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • 0.55-0.59 m2 BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
    • ≥ 0.6 m2 BSA: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 31 through 34, 37, 38, 40
  • Dactinomycin (Cosmegen) by the following weight-based criteria:
    • 3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • 12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
    • ≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 34, 40
  • Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 220 mg IV over 60 minutes on day 1 of weeks 34, 40
    • 0.3-0.34 m2 BSA: 280 mg IV over 60 minutes on day 1 of weeks 34, 40
    • 0.35-0.39 m2 BSA: 360 mg IV over 60 minutes on day 1 of weeks 34, 40
    • 0.4-0.44 m2 BSA: 440 mg IV over 60 minutes on day 1 of weeks 34, 40
    • 0.45-0.49 m2 BSA: 520 mg IV over 60 minutes on day 1 of weeks 34, 40
    • 0.5-0.54 m2 BSA: 600 mg IV over 60 minutes on day 1 of weeks 34, 40
    • 0.55-0.59 m2 BSA: 660 mg IV over 60 minutes on day 1 of weeks 34, 40
    • ≥ 0.6 m2 BSA: 1200 mg/m2 IV over 60 minutes on day 1 of weeks 34, 40
  • Irinotecan (Camptosar) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 8 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • 0.3-0.34 m2 BSA: 12 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • 0.35-0.39 m2 BSA: 15 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • 0.4-0.44 m2 BSA: 18 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • 0.45-0.49 m2 BSA: 22 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • 0.5-0.54 m2 BSA: 24 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • 0.55-0.59 m2 BSA: 28 mg IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37
    • ≥ 0.6 m2 BSA: 50 mg/m2 IV over 90 minutes once daily on days 1 through 5 of weeks 31, 37

Supportive Medications

Mesna (Mesnex) can also be given PO at twice the IV dose

Protocol, Maintenance Cycles 1-6

Chemotherapy

  • Vinorelbine (Navelbine) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 4 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • 0.3-0.34 m2 BSA: 6 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • 0.35-0.39 m2 BSA: 7.5 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • 0.4-0.44 m2 BSA: 9 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • 0.45-0.49 m2 BSA: 11 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • 0.5-0.54 m2 BSA: 12 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • 0.55-0.59 m2 BSA: 14 mg IV push over 6 to 10 minutes on days 1, 8, and 15
    • ≥ 0.6 m2 BSA: 25 mg/m2 IV push over 6 to 10 minutes on days 1, 8, and 15
  • Cyclophosphamide (Cytoxan) 25 mg/m2 PO once daily on days 1 through 28
    • Dose rounded to the nearest 25 mg capsule

28-day cycle

References

  1. Vinorelbine and low dose cyclophosphamide maintenance therapy: Vinorelbine and low dose cyclophosphamide maintenance therapy: Bisogno G, De Salvo GL, Bergeron C, Gallego Melcons s, Merks JH, Kelsey A, Martelli H, Minard-Colin V, Orbach D, Glosli H, Chisholm J, Casanova M, Zanetti I, Devalck C, Ben-Arush M, Mudry P, Ferman S, Jenney M, Ferrari A. Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 tial. Lancet Oncol. 2019 Nov;20(11):1566-1575. link to original article PubMed
  2. COG ARST1431: NCT02567435

COG ARST0531 VAC Arm

Protocol, Weeks 1-15

Chemotherapy, Week 1

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 1

Chemotherapy, Week 2

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 3

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 4

  • Radiation therapy begins
  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 4

Chemotherapy, Week 5

  • Radiation therapy continues
  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 6

  • Radiation therapy continues
  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 7

  • Radiation therapy continues
  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 7

Chemotherapy, Week 8

  • Radiation therapy continues
  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 9

  • Radiation therapy final week
  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 10

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 10

Chemotherapy, Week 11

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 12

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 13

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 13

Chemotherapy, Week 14 Off Chemo

Chemotherapy, Week 15 Evaluation

Protocol, Weeks 16-30

Chemotherapy, Week 16

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 16

Chemotherapy, Week 17 Off Chemo

Chemotherapy, Week 18 Off Chemo

Chemotherapy, Week 19

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 19

Chemotherapy, Week 20

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 21

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 22

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 22

Chemotherapy, Week 23

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 24

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 25

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 25

Chemotherapy, Week 26 Off Chemo

Chemotherapy, Week 27 Off Chemo

Chemotherapy, Week 28

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 28

Chemotherapy, Week 29 Off Chemo

Chemotherapy, Week 30 Evaluation

Protocol, Weeks 31-43

Chemotherapy, Week 31

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 31

Chemotherapy, Week 32

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 33

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 34

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 34

Chemotherapy, Week 35

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 36

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 37

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 37

Chemotherapy, Week 38 Off Chemo

Chemotherapy, Week 39 Off Chemo

Chemotherapy, Week 40

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 40

Chemotherapy, Week 41 Off Chemo

Chemotherapy, Week 42 Off Chemo

Chemotherapy, Week 43 Evaluation

References

  1. COG ARST0531: Hawkins DS, Chi Y, Anderson JR, Tian, J, Arndt CAS, Bomgaars L, Donaldson SS, Hayes-Jordan A, Mascarenhas L, McCarville MB, McCune JS, McCowage G, Million L, Morris CD, Parham DM, Rodeberg DA, Rudzinski ER, Shnorhavorian M, Spunt SL, Skapek SX, Teot LA, Wolden S, Yock TI, Meyer WH. Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve OUtcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2018 Sep;36(27):2770-2777. link to original article PubMed PMC Article NCT01222715

COG ARST0531 VAC/VI Arm

Protocol, Weeks 1-15

Chemotherapy, Week 1

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 1

Chemotherapy, Week 2

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 3

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 4

  • Radiation therapy begins
  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 5

  • Radiation therapy continues
  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 6

  • Radiation therapy continues
  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 7

  • Radiation therapy continues
  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 8

  • Radiation therapy continues
  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 9

  • Radiation therapy final week
  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 10

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 10

Chemotherapy, Week 11

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 12

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 13

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 13

Chemotherapy, Week 14 Off Chemo

Chemotherapy, Week 15 Evaluation

Protocol, Weeks 16-30

Chemotherapy, Week 16

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 17

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 18 Off Chemo

Chemotherapy, Week 19

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 20

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 21 Off Chemo

Chemotherapy, Week 22

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 22

Chemotherapy, Week 23

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 24

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 25

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 26

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 27 Off Chemo

Chemotherapy, Week 28

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 28

Chemotherapy, Week 29 Off Chemo

Chemotherapy, Week 30 Evaluation

Protocol, Weeks 31-43

Chemotherapy, Week 31

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 32

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 33

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 34

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 34

Chemotherapy, Week 35 Off Chemo

Chemotherapy, Week 36 Off Chemo

Chemotherapy, Week 37

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 90 minutes once per day on days 1 through 5

Chemotherapy, Week 38

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 39 Off Chemo

Chemotherapy, Week 40

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1
  • Mesna (Mesnex) by the following age-based criteria:

Chemotherapy, Week 41 Off Chemo

Chemotherapy, Week 42 Off Chemo

Chemotherapy, Week 43 Evaluation

References

  1. COG ARST0531: Hawkins DS, Chi Y, Anderson JR, Tian, J, Arndt CAS, Bomgaars L, Donaldson SS, Hayes-Jordan A, Mascarenhas L, McCarville MB, McCune JS, McCowage G, Million L, Morris CD, Parham DM, Rodeberg DA, Rudzinski ER, Shnorhavorian M, Spunt SL, Skapek SX, Teot LA, Wolden S, Yock TI, Meyer WH. Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve OUtcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2018 Sep;36(27):2770-2777. link to original article PubMed PMC Article NCT01222715

Low Risk

COG ARST1431 Protocol C (VAC/VA Only)

Protocol, Cycles 1-4 (Weeks 1 through 12)

Chemotherapy

  • Vincristine (Oncovin) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
    • 0.3-0.34 m2 BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
    • 0.35-0.39 m2 BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
    • 0.4-0.44 m2 BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
    • 0.45-0.49 m2 BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
    • 0.5-0.54 m2 BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
    • 0.55-0.59 m2 BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
    • ≥ 0.6 m2 BSA: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 1 through 10
  • Dactinomycin (Cosmegen) by the following weight-based criteria:
    • 3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
    • 4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
    • 6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
    • 7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
    • 8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
    • 10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
    • 11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
    • 12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
    • ≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 1, 4, 7, 10
  • Cyclophosphamide (Cytoxan) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 220 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
    • 0.3-0.34 m2 BSA: 280 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
    • 0.35-0.39 m2 BSA: 360 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
    • 0.4-0.44 m2 BSA: 440 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
    • 0.45-0.49 m2 BSA: 520 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
    • 0.5-0.54 m2 BSA: 600 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
    • 0.55-0.59 m2 BSA: 660 mg IV over 60 minutes on day 1 of weeks 1, 4, 7, 10
    • ≥ 0.6 m2 BSA: 1200 mg/m2 IV over 60 minutes on day 1 of weeks 1, 4, 7, 10

Supportive Medications

Protocol, Cycles 5-8 (Weeks 13 through 24)

Chemotherapy

  • Vincristine (Oncovin) by the following BSA-based criteria:
    • 0.25-0.29 m2 BSA: 0.24 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
    • 0.3-0.34 m2 BSA: 0.34 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
    • 0.35-0.39 m2 BSA: 0.44 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
    • 0.4-0.44 m2 BSA: 0.55 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
    • 0.45-0.49 m2 BSA: 0.65 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
    • 0.5-0.54 m2 BSA: 0.74 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
    • 0.55-0.59 m2 BSA: 0.8 mg IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
    • ≥ 0.6 m2 BSA: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute (or infusion via minibag as per institutional policy once weekly on day 1 of weeks 13 through 22
  • Dactinomycin (Cosmegen) by the following weight-based criteria:
    • 3-4.5 kg: 0.09 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
    • 4.6-6 kg: 0.14 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
    • 6.1-7.3 kg: 0.21 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
    • 7.4-8.6 kg: 0.26 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
    • 8.7-9.9 kg: 0.33 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
    • 10-11.2 kg: 0.4 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
    • 11.3-12.5 kg: 0.5 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
    • 12.6-13.9 kg: 0.6 mg slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22
    • ≥14 kg: 0.05 mg/kg (maximum dose of 2.5 mg) slow IV push over 1 to 5 minutes or IV infusion over 10 to 15 minutes on day 1 of weeks 13, 16, 19, 22

References

  1. Vinorelbine and low dose cyclophosphamide maintenance therapy: Vinorelbine and low dose cyclophosphamide maintenance therapy: Bisogno G, De Salvo GL, Bergeron C, Gallego Melcons s, Merks JH, Kelsey A, Martelli H, Minard-Colin V, Orbach D, Glosli H, Chisholm J, Casanova M, Zanetti I, Devalck C, Ben-Arush M, Mudry P, Ferman S, Jenney M, Ferrari A. Vinorelbine and continuous low-dose cyclophosphamide as maintenance chemotherapy in patients with high-risk rhabdomyosarcoma (RMS 2005): a multicentre, open-label, randomised, phase 3 tial. Lancet Oncol. 2019 Nov;20(11):1566-1575. link to original article PubMed
  2. COG ARST1431: NCT02567435

COG ARST0331 (In Process)

High Risk

COG ARST0431

Protocol, Weeks 1-6

Chemotherapy, Week 1 (IRIN-VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5

Chemotherapy, Week 2 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 3 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 4 (IRIN-VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5

Chemotherapy, Week 5 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 6 Evaluation

Protocol, Weeks 7-19

Chemotherapy, Week 7 (VDC)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Doxorubicin (Adriamycin) by the following age-based criteria:
    • Age ≥ 1 year: 37.5 mg/m2 (Total dose per week of 75 mg/m2) IV over 24 hours once per day on days 1 through 2
    • Age < 1 year: 18.75 mg/m2 IV over 24 hours once per day on days 1 through 2
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 7

Chemotherapy, Week 8 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 9 (IE)

  • Ifosfamide (Ifex) by the following age-based criteria:
    • Age ≥ 1 year: 1800 mg/m2 IV over 1 hour once per day on days 1 through 5
    • Age < 1 year: 900 mg/m2 IV over 1 hour once per day on days 1 through 5
  • Etoposide (Vepesid) by the following age-based criteria:
    • Age ≥ 1 year: 100 mg/m2 IV over 30 to 60 minutes once per day on days 1 through 5
    • Age < 1 year: 50 mg/m2 IV over 30 to 60 minutes once per day on days 1 through 5

Supportive Medications, Week 9

  • Mesna (Mesnex) by the following age-based criteria:
    • Age ≥ 3 years: 360 mg/m2 at hour 0, 4, and 8 from the start of each Ifosfamide (Ifex) infusion on days 1 through 5
    • Age < 3 years: 180 mg/m2 at hour 0, 4, and 8 from the start of each Ifosfamide (Ifex) infusion on days 1 through 5

Chemotherapy, Week 10 Off Chemo

Chemotherapy, Week 11 (VDC)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Doxorubicin (Adriamycin) by the following age-based criteria:
    • Age ≥ 1 year: 37.5 mg/m2 (Total dose per week of 75 mg/m2) IV over 24 hours once per day on days 1 through 2
    • Age < 1 year: 18.75 mg/m2 IV over 24 hours once per day on days 1 through 2
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 11

Chemotherapy, Week 12 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 13 (IE)

  • Ifosfamide (Ifex) by the following age-based criteria:
    • Age ≥ 1 year: 1800 mg/m2 IV over 1 hour once per day on days 1 through 5
    • Age < 1 year: 900 mg/m2 IV over 1 hour once per day on days 1 through 5
  • Etoposide (Vepesid) by the following age-based criteria:
    • Age ≥ 1 year: 100 mg/m2 IV over 30 to 60 minutes once per day on days 1 through 5
    • Age < 1 year: 50 mg/m2 IV over 30 to 60 minutes once per day on days 1 through 5

Supportive Medications, Week 13

  • Mesna (Mesnex) by the following age-based criteria:
    • Age ≥ 3 years: 360 mg/m2 at hour 0, 4, and 8 from the start of each Ifosfamide (Ifex) infusion on days 1 through 5
    • Age < 3 years: 180 mg/m2 at hour 0, 4, and 8 from the start of each Ifosfamide (Ifex) infusion on days 1 through 5

Chemotherapy, Week 14 Off Chemo

Chemotherapy, Week 15 (VDC)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Doxorubicin (Adriamycin) by the following age-based criteria:
    • Age ≥ 1 year: 37.5 mg/m2 (Total dose per week of 75 mg/m2) IV over 24 hours once per day on days 1 through 2
    • Age < 1 year: 18.75 mg/m2 IV over 24 hours once per day on days 1 through 2
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 15

Chemotherapy, Week 16 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 17 (IE)

  • Ifosfamide (Ifex) by the following age-based criteria:
    • Age ≥ 1 year: 1800 mg/m2 IV over 1 hour once per day on days 1 through 5
    • Age < 1 year: 900 mg/m2 IV over 1 hour once per day on days 1 through 5
  • Etoposide (Vepesid) by the following age-based criteria:
    • Age ≥ 1 year: 100 mg/m2 IV over 30 to 60 minutes once per day on days 1 through 5
    • Age < 1 year: 50 mg/m2 IV over 30 to 60 minutes once per day on days 1 through 5

Supportive Medications, Week 17

  • Mesna (Mesnex) by the following age-based criteria:
    • Age ≥ 3 years: 360 mg/m2 at hour 0, 4, and 8 from the start of each Ifosfamide (Ifex) infusion on days 1 through 5
    • Age < 3 years: 180 mg/m2 at hour 0, 4, and 8 from the start of each Ifosfamide (Ifex) infusion on days 1 through 5

Chemotherapy, Week 18 Off Chemo

Chemotherapy, Week 19 Evaluation

Protocol, Weeks 20-34

Chemotherapy, Week 20 (IRIN-VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5

Chemotherapy, Week 21 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 22 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 23 (IRIN-VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5

Chemotherapy, Week 24 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 25 Off Chemo

Chemotherapy, Week 26 (IE)

  • Ifosfamide (Ifex) by the following age-based criteria:
    • Age ≥ 1 year: 1800 mg/m2 IV over 1 hour once per day on days 1 through 5
    • Age < 1 year: 900 mg/m2 IV over 1 hour once per day on days 1 through 5
  • Etoposide (Vepesid) by the following age-based criteria:
    • Age ≥ 1 year: 100 mg/m2 IV over 30 to 60 minutes once per day on days 1 through 5
    • Age < 1 year: 50 mg/m2 IV over 30 to 60 minutes once per day on days 1 through 5

Supportive Medications, Week 26

  • Mesna (Mesnex) by the following age-based criteria:
    • Age ≥ 3 years: 360 mg/m2 at hour 0, 4, and 8 from the start of each Ifosfamide (Ifex) infusion on days 1 through 5
    • Age < 3 years: 180 mg/m2 at hour 0, 4, and 8 from the start of each Ifosfamide (Ifex) infusion on days 1 through 5

Chemotherapy, Week 27 Off Chemo

Chemotherapy, Week 28 (VDC)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Doxorubicin (Adriamycin) by the following age-based criteria:
    • Age ≥ 1 year: 37.5 mg/m2 (Total dose per week of 75 mg/m2) IV over 24 hours once per day on days 1 through 2
    • Age < 1 year: 18.75 mg/m2 IV over 24 hours once per day on days 1 through 2
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 28

Chemotherapy, Week 29 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 30 (IE)

  • Ifosfamide (Ifex) by the following age-based criteria:
    • Age ≥ 1 year: 1800 mg/m2 IV over 1 hour once per day on days 1 through 5
    • Age < 1 year: 900 mg/m2 IV over 1 hour once per day on days 1 through 5
  • Etoposide (Vepesid) by the following age-based criteria:
    • Age ≥ 1 year: 100 mg/m2 IV over 30 to 60 minutes once per day on days 1 through 5
    • Age < 1 year: 50 mg/m2 IV over 30 to 60 minutes once per day on days 1 through 5

Supportive Medications, Week 30

  • Mesna (Mesnex) by the following age-based criteria:
    • Age ≥ 3 years: 360 mg/m2 at hour 0, 4, and 8 from the start of each Ifosfamide (Ifex) infusion on days 1 through 5
    • Age < 3 years: 180 mg/m2 at hour 0, 4, and 8 from the start of each Ifosfamide (Ifex) infusion on days 1 through 5

Chemotherapy, Week 31 Off Chemo

Chemotherapy, Week 32 (VDC)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Doxorubicin (Adriamycin) by the following age-based criteria:
    • Age ≥ 1 year: 37.5 mg/m2 (Total dose per week of 75 mg/m2) IV over 24 hours once per day on days 1 through 2
    • Age < 1 year: 18.75 mg/m2 IV over 24 hours once per day on days 1 through 2
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 32

Chemotherapy, Week 33 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 34 Evaluation

Protocol, Weeks 35-54

Chemotherapy, Week 35 (VAC)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 35

Chemotherapy, Week 36 Off Chemo

Chemotherapy, Week 37 Off Chemo

Chemotherapy, Week 38 (VAC)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 38

Chemotherapy, Week 39 Off Chemo

Chemotherapy, Week 40 Off Chemo

Chemotherapy, Week 41 (VAC)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 41

Chemotherapy, Week 42 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 43 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 44 (VAC)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Dactinomycin (Cosmegen) by the following age-based criteria:
    • Age ≥ 1 year: 0.045 mg/kg (maximum dose of 2.5 mg) IV push over 1 to 5 minutes once per day on day 1
    • Age < 1 year: 0.025 mg/kg IV over 1 to 5 minutes once per day on day 1
  • Cyclophosphamide (Cytoxan) by the following age-based criteria:
    • Age ≥ 3 years: 1200 mg/m2 IV over 1 hour once per day on day 1
    • Age < 3 years: 40mg/kg IV over 1 hour once per day on day 1

Supportive Medications, Week 44

Chemotherapy, Week 45 Off Chemo

Chemotherapy, Week 46 Off Chemo

Chemotherapy, Week 47 (IRIN-VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5

Chemotherapy, Week 48 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 49 Off Chemo

Chemotherapy, Week 50 (IRIN-VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1
  • Irinotecan (Camptosar) 50 mg/m2 (maximum dose of 100 mg/day) IV over 60 minutes once per day on days 1 through 5

Chemotherapy, Week 51 (VCR)

  • Vincristine (Oncovin) by the following age-based criteria:
    • Age ≥ 3 years: 1.5 mg/m2 (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age ≥ 1 year to < 3 years: 0.05 mg/kg (maximum dose of 2 mg) IV push over 1 minute once on day 1
    • Age < 1 year: 0.025 mg/kg IV push over 1 minute once on day 1

Chemotherapy, Week 52 Off Chemo

Chemotherapy, Week 53 Off Chemo

Chemotherapy, Week 54 Evaluation

References

  1. COG ARST0431: Weigel BJ, Lyden E, Anderson JR, Meyer WH, Parham DM, Rodeberg DA, Michalski JM, Hawkins DS, Arndt CAS. 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. Journal of Clinical Oncology. 2016 Oct;34(2):117-122. link to original article link to PMC article PubMed NCT00354744
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