Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
</div>
 
</div>
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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? Please go to the [[Follicular_lymphoma|main follicular lymphoma regimen page]] to find other regimens.
+
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Hodgkin_lymphoma|main Hodgkin lymphoma page]] for current regimens.
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
 
|<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: #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>
−
|}  
+
|}
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
−
''Note: Some of these regimens are not specific to follicular lymphoma because they were published before the modern classification schema was finalized. That said, most indolent lymphomas are follicular lymphoma and unless otherwise specified these should be assumed to be germane to follicular lymphoma.''
+
=Untreated=
−
=First-line therapy=
+
==ABVDm {{#subobject:3065be|Regimen=1}}==
−
==CHOP {{#subobject:39e6ac|Regimen=1}}==
+
ABVDm: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine, '''<u>m</u>'''ethylprednisolone
−
CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, capped vincristine {{#subobject:d78eb4|Variant=1}}===
+
===Regimen {{#subobject:c39ab4|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 23: Line 22:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1002/cncr.22093 Nickenig et al. 2006 (GLSG '96)]
+
|[http://www.bloodjournal.org/content/103/1/58.long Le Maignan et al. 2003 (H90-NM)]
−
|1996-1998
+
|1990-1996
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#MCP|MCP]]
+
|[[#EBVMm_99|EBVMm]]
−
|style="background-color:#d9ef8b"|Might have superior CR rate
+
| style="background-color:#ffffbf" |Seems not superior
−
|-
 
−
|[http://www.bloodjournal.org/content/106/12/3725.long Hiddemann et al. 2005 (GLSG '00)]
 
−
|2000-2003
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Follicular_lymphoma#R-CHOP|R-CHOP]]
 
−
|style="background-color:#d73027"|Inferior OS
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Doxorubicin (Adriamycin)]]
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Bleomycin (Blenoxane)]]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Vinblastine (Velban)]]
 +
*[[Dacarbazine (DTIC)]]
 +
====Glucocorticoid therapy====
 +
*[[Methylprednisolone (Solumedrol)]]
 +
</div></div>
 +
===References===
 +
# '''H90-NM:''' Le Maignan C, Desablens B, Delwail V, Dib M, Berthou C, Vigier M, Ghandour C, Atmani S, Casassus P, Maisonneuve H, Le Mevel A, Traulle C, Bernard M, Briere J, Colonna P, Andrieu JM. Three cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) or epirubicin, bleomycin, vinblastine, and methotrexate (EBVM) plus extended field radiation therapy in early and intermediate Hodgkin disease: 10-year results of a randomized trial. Blood. 2004 Jan 1;103(1):58-66. Epub 2003 Aug 7. [http://www.bloodjournal.org/content/103/1/58.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/12907440 PubMed]
 +
==ABVE-PC {{#subobject:c24d93|Regimen=1}}==
 +
ABVE-PC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>C</u>'''yclophosphamide
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 3 cycles with response adaptation {{#subobject:14cd95|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/PMC2744567/ Schwartz et al. 2009 (POG P9425)]
 +
| style="background-color:#91cf61" |Phase 2
 +
|-
 +
|}''This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''
 +
====Chemotherapy====
 +
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1
 +
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7
 +
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7
 +
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4
 +
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7
−
'''21-day cycle for 6 to 8 cycles'''
+
====Supportive therapy====
 +
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)
 +
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)
 +
'''21-day cycle for 3 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*Rapid early responders: [[#Radiation_therapy_2|IFRT]] consolidation x 21 Gy
 +
*Slow early responders: [[#ABVE-PC|ABVE-PC]] x 2 (5 cycles total), then [[#Radiation_therapy_2|IFRT]] consolidation x 21 Gy
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, uncapped vincristine {{#subobject:22ca16|Variant=1}}===
+
===Regimen variant #4, 5 cycles {{#subobject:7e95ea|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"
−
!style="width: 20%"|Study
+
! style="width: 25%" |Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!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.2004.07.170 Zinzani et al. 2004]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (POG P9425)]
−
|1999-2002
+
| style="background-color:#91cf61" |Phase 2
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#FM|FM]]
 
−
|style="background-color:#d73027"|Inferior CR rate
 
 
|-
 
|-
−
|}
+
|}''This regimen is intended for pediatric patients, younger than 22 years old, who are slow early responders. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[#ABVE-PC|ABVE-PC]] x 3, with slow early response
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Doxorubicin (Adriamycin)]] 30 mg/m<sup>2</sup> IV once per day on days 0 & 1
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV or SC once per day on days 0 & 7
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
+
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2.8 mg) IV once per day on days 0 & 7
 +
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 0 to 4
 +
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 0
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
+
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 0 to 7
−
'''21-day cycle for 6 cycles'''
+
====Supportive therapy====
 +
*[[Dexrazoxane (Zinecard)]] 300 mg/m<sup>2</sup> IV once per day on days 0, 1, 7 (this was a randomization)
 +
*[[Filgrastim (Neupogen)]] 5 mcg/kg IV or SC once per day from day 5 until neutrophil recovery (held on day 7)
 +
'''21-day cycle for 5 cycles, including the first 3 cycles'''
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#cbd5e7">
 
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*Patients with PR or CR with detectable bcl-2/IgH fusion by PCR: [[Follicular_lymphoma#Rituximab_monotherapy.2C_abbreviated_course|R]] x 4
+
*[[#Radiation_therapy_2|IFRT]] consolidation x 21 Gy
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Zinzani PL, Pulsoni A, Perrotti A, Soverini S, Zaja F, De Renzo A, Storti S, Lauta VM, Guardigni L, Gentilini P, Tucci A, Molinari AL, Gobbi M, Falini B, Fattori PP, Ciccone F, Alinari L, Martelli M, Pileri S, Tura S, Baccarani M. Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma. J Clin Oncol. 2004 Jul 1;22(13):2654-61. Epub 2004 May 24. [https://doi.org/10.1200/jco.2004.07.170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15159414 PubMed]
+
#'''POG P9425:''' Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 [http://www.bloodjournal.org/content/114/10/2051.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19584400 PubMed] NCT00005578
−
# '''GLSG '00:''' Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wörmann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trümper L, Aldaoud A, Parwaresch R, Unterhalt M. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. Epub 2005 Aug 25. [http://www.bloodjournal.org/content/106/12/3725.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16123223 PubMed]
+
==BCVPP {{#subobject:75779b|Regimen=1}}==
−
# '''GELA GELF-94:''' Sebban C, Mounier N, Brousse N, Belanger C, Brice P, Haioun C, Tilly H, Feugier P, Bouabdallah R, Doyen C, Salles G, Coiffier B. Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood. 2006 Oct 15;108(8):2540-4. Epub 2006 Jul 11. [http://www.bloodjournal.org/content/108/8/2540.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/16835383 PubMed] NCT00140569
+
BCVPP: '''<u>B</u>'''CNU (Carmustine), '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
−
# '''GLSG '96:''' Nickenig C, Dreyling M, Hoster E, Pfreundschuh M, Trumper L, Reiser M, Wandt H, Lengfelder E, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. Combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) improves response rates but not survival and has lower hematologic toxicity compared with combined mitoxantrone, chlorambucil, and prednisone (MCP) in follicular and mantle cell lymphomas: results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group. Cancer. 2006 Sep 1;107(5):1014-22. [https://doi.org/10.1002/cncr.22093 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16878325 PubMed]
 
−
==CHOP-B {{#subobject:bb947|Regimen=1}}==
 
−
CHOP-B: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne, '''<u>B</u>'''leomycin
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:4f9502|Variant=1}}===
+
===Regimen {{#subobject:ab3db2|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 90: Line 116:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2003.05.128 Peterson et al. 2003 (CALGB 7951)]
+
|[https://doi.org/10.1002/1097-0142%28197811%2942%3A5%3C2101%3A%3AAID-CNCR2820420504%3E3.0.CO%3B2-M Durant et al. 1978]
−
|1980-1985
+
|1971-1975
 +
| style="background-color:#91cf61" |Non-randomized portion of RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://doi.org/10.7326/0003-4819-101-4-447 Bakemeier et al. 1984]
 +
|1972-1976
 
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
|style="background-color:#1a9851"|Phase 3 (E-esc)
−
|[[Follicular_lymphoma#Cyclophosphamide_monotherapy|Cyclophosphamide]]
+
|[[Hodgkin_lymphoma#MOPP|MOPP]]
−
|style="background-color:#ffffbf"|Did not meet primary endpoint of OS
+
|style="background-color:#ffffbf"|Seems not superior<sup>1</sup>
 
|-
 
|-
 
|}
 
|}
 +
''<sup>1</sup>For patients achieving CR, this regimen seemed to have comparatively superior survival.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Carmustine (BCNU)]]
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Vincristine (Oncovin)]]
−
*[[Bleomycin (Blenoxane)]] as follows:
+
*[[Procarbazine (Matulane)]]
−
**Cycles 1 to 6: 10 units/m<sup>2</sup> IM once on day 1
 
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
*[[Prednisone (Sterapred)]]
−
'''21-day cycle for 6 cycles, then 28-day cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''CALGB 7951:''' Peterson BA, Petroni GR, Frizzera G, Barcos M, Bloomfield CD, Nissen NI, Hurd DD, Henderson ES, Sartiano GP, Johnson JL, Holland JF, Gottlieb AJ. Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the Cancer and Leukemia Group B. J Clin Oncol. 2003 Jan 1;21(1):5-15. [https://doi.org/10.1200/jco.2003.05.128 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12506163 PubMed]
+
# Durant JR, Gams RA, Velez-Garcia E, Bartolucci A, Wirtschafter D, Dorfman R. BCNU, velban, cyclophosphamide, procarbazine, and prednisone (BVCPP) in advanced Hodgkin's disease. Cancer. 1978 Nov;42(5):2101-10. [https://doi.org/10.1002/1097-0142%28197811%2942%3A5%3C2101%3A%3AAID-CNCR2820420504%3E3.0.CO%3B2-M link to original article] [https://pubmed.ncbi.nlm.nih.gov/719600 PubMed]
−
==CHOP, then <sup>131</sup>Iodine-Tositumomab {{#subobject:57fff5|Regimen=1}}==
+
# Bakemeier RF, Anderson JR, Costello W, Rosner G, Horton J, Glick JH, Hines JD, Berard CW, DeVita VT Jr; [[Study_Groups#ECOG|ECOG]]. BCVPP chemotherapy for advanced Hodgkin's disease: evidence for greater duration of complete remission, greater survival, and less toxicity than with a MOPP regimen: results of the Eastern Cooperative Oncology Group study. Ann Intern Med. 1984 Oct;101(4):447-56. [https://doi.org/10.7326/0003-4819-101-4-447 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6089632 PubMed]
−
CHOP-RIT: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne '''<u>R</u>'''adio'''<u>I</u>'''mmuno'''<u>T</u>'''herapy
+
==ChlVPP/PABIOE {{#subobject:8ee324|Regimen=1}}==
 +
ChlVPP/PABIOE: '''<u>Chl</u>'''orambucil, '''<u>V</u>'''inblastine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>P</u>'''rednisolone, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:8c52b8|Variant=1}}===
+
===Protocol {{#subobject:48feb0|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 121: Line 153:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/102/5/1606.long Press et al. 2003 (SWOG S9911)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363648/ Hancock et al. 2001]
−
|1999-2000
+
|1992-1996
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#1a9851" |Randomized (C)
−
|style="background-color:#d3d3d3"|
+
|[[#PABIOE_99|PABIOE]]
−
|style="background-color:#d3d3d3"|
+
| style="background-color:#1a9850" |Superior OS
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732010/ Press et al. 2012 (SWOG S0016)]
 
−
|2001-2008
 
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
 
−
|[[Follicular_lymphoma#R-CHOP|R-CHOP]]
 
−
| style="background-color:#1a9850" |Superior PFS<sup>1</sup>
 
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>Reported efficacy for SWOG S0016 is based on the 2018 update.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy, CHOP portion====
+
====Chemotherapy, ChlVPP portion====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Chlorambucil (Leukeran)]]
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Vinblastine (Velban)]]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Procarbazine (Matulane)]]
−
====Glucocorticoid therapy, CHOP portion====
+
====Glucocorticoid therapy, ChlVPP portion====
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
+
*[[Prednisolone (Millipred)]]
−
====Supportive therapy====
+
====Glucocorticoid therapy, PABIOE portion====
−
*[[Allopurinol (Zyloprim)]] 300 mg PO once per day for patients with bulky disease
+
*[[Prednisolone (Millipred)]]
−
'''21-day cycle for 6 cycles, followed by:'''
+
====Chemotherapy, PABIOE portion====
−
====Radioconjugate therapy, dosimetric step====
+
*[[Doxorubicin (Adriamycin)]]
−
*On Day 1, infusions of:
+
*[[Bleomycin (Blenoxane)]]
−
**Tositumomab 450 mg IV over 1 hour
+
*[[Vincristine (Oncovin)]]
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
+
*[[Etoposide (Vepesid)]]  
−
**First scan of whole body dosimetry & redistribution within 1 hour of finishing dosimetric dose on day 1
 
−
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 
−
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO three times per day, Lugol solution 20 drops PO three times per day, or potassium iodide tablets 130 mg PO once per day, starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion
 
−
====Radioconjugate therapy, therapeutic step====
 
−
*Any one day 7 to 14 days after dosimetric infusion, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour, given first
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 
−
***65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3
 
−
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO three times per day, Lugol solution 20 drops PO three times per day, or potassium iodide tablets 130 mg PO once per day, starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''SWOG S9911:''' Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, LeBlanc M, Gaynor ER, Rivkin SE, Fisher RI. A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin lymphoma: Southwest Oncology Group Protocol S9911. Blood. 2003 Sep 1;102(5):1606-12. Epub 2003 May 8. [http://www.bloodjournal.org/content/102/5/1606.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12738671 PubMed] NCT00003784
+
# Hancock BW, Gregory WM, Cullen MH, Hudson GV, Burton A, Selby P, Maclennan KA, Jack A, Bessell EM, Smith P, Linch DC; British National Lymphoma Investigation; Central Lymphoma Group. ChlVPP alternating with PABlOE is superior to PABlOE alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation/Central Lymphoma Group randomized controlled trial. Br J Cancer. 2001 May 18;84(10):1293-300. [https://doi.org/10.1054/bjoc.2001.1778 link to orginal article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363648/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/11355937 PubMed]
−
## '''Update:''' Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, Leblanc M, Fisher RI; [[Study_Groups#SWOG|SWOG]]. Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin's lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol. 2006 Sep 1;24(25):4143-9. Epub 2006 Aug 8. [https://doi.org/10.1200/jco.2006.05.8198 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16896003 PubMed]
+
# '''UKLG LY09:''' Johnson PW, Radford JA, Cullen MH, Sydes MR, Walewski J, Jack AS, MacLennan KA, Stenning SP, Clawson S, Smith P, Ryder D, Hancock BW; United Kingdom Lymphoma Group. Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol. 2005 Dec 20;23(36):9208-18. Epub 2005 Nov 28. [https://doi.org/10.1200/JCO.2005.03.2151 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16314615 PubMed] ISRCTN97144519
−
# '''SWOG S0016:''' Press OW, Unger JM, Rimsza LM, Friedberg JW, LeBlanc M, Czuczman MS, Kaminski M, Braziel RM, Spier C, Gopal AK, Maloney DG, Cheson BD, Dakhil SR, Miller TP, Fisher RI. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus 131Iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol. 2013 Jan 20;31(3):314-20. Epub 2012 Dec 10. [https://doi.org/10.1200/jco.2012.42.4101 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732010/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23233710 PubMed] NCT00006721
+
## '''Subgroup analysis:''' Johnson PW, Sydes MR, Hancock BW, Cullen M, Radford JA, Stenning SP. Consolidation radiotherapy in patients with advanced Hodgkin's lymphoma: survival data from the UKLG LY09 randomized controlled trial (ISRCTN97144519). J Clin Oncol. 2010 Jul 10;28(20):3352-9. Epub 2010 May 24. [https://doi.org/10.1200/JCO.2009.26.0323 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20498402 PubMed]
−
## '''Update:''' Shadman M, Li H, Rimsza L, Leonard JP, Kaminski MS, Braziel RM, Spier CM, Gopal AK, Maloney DG, Cheson BD, Dakhil S, LeBlanc M, Smith SM, Fisher RI, Friedberg JW, Press OW. Continued excellent outcomes in previously untreated patients with follicular lymphoma after treatment with CHOP plus rituximab or CHOP plus (131)I-tositumomab: long-term follow-up of phase III randomized study SWOG-S0016. J Clin Oncol. 2018 Mar 1;36(7):697-703. Epub 2018 Jan 22. [https://doi.org/10.1200/JCO.2017.74.5083 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29356608 PubMed]
+
==COMP {{#subobject:8ee324|Regimen=1}}==
−
==CHVP {{#subobject:4dd34a|Regimen=1}}==
+
COMP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>M</u>'''ethotrexate, '''<u>P</u>'''rednisone
−
CHVP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>V</u>'''umon (Teniposide), '''<u>P</u>'''rednisone
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:bb6c6f|Variant=1}}===
+
===Regimen {{#subobject:48feb0|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"
−
!style="width: 20%"|Study
+
!style="width: 25%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!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/NEJM199311253292203 Solal-Celigny et al. 1993 (GELA GELF-86)]
+
|[http://cancerres.aacrjournals.org/content/27/7/1258.long Moxley et al. 1967]
−
|1986-1991
+
| style="background-color:#ffffbe" |Pilot
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#CHVP-I|CHVP-I]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]]
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once on day 1
+
*[[Vincristine (Oncovin)]]
−
*[[Teniposide (Vumon)]] 60 mg/m<sup>2</sup> IV once on day 1
+
*[[Methotrexate (MTX)]]
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
*[[Prednisone (Sterapred)]]
−
'''1-month cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*SD or better: [[#CHVP_88|CHVP]] maintenance
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''GELA GELF-86:''' Solal-Celigny P, Lepage E, Brousse N, Reyes F, Haioun C, Leporrier M, Peuchmaur M, Bosly A, Parlier Y, Brice P, Coiffier B, Gisselbrecht C; Groupe d'Etude des Lymphomes de l'Adulte. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. N Engl J Med. 1993 Nov 25;329(22):1608-14. [https://doi.org/10.1056/NEJM199311253292203 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8232429 PubMed]
+
# Moxley JH 3rd, De Vita VT, Brace K, Frei E 3rd. Intensive combination chemotherapy and X-irradiation in Hodgkin's disease. Cancer Res. 1967 Jul;27(7):1258-63. [http://cancerres.aacrjournals.org/content/27/7/1258.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/4952914 PubMed]
−
==CHVP-I {{#subobject:b8f655|Regimen=1}}==
+
==COPP (CCNU) {{#subobject:86879b|Regimen=1}}==
−
CHVP-I: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>V</u>'''umon (Teniposide), '''<u>P</u>'''rednisone, '''<u>I</u>'''nterferon alfa-2b
+
COPP: '''<u>C</u>'''CNU (Lomustine), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:697b4f|Variant=1}}===
+
===Regimen {{#subobject:cf3db2|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 216: Line 212:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1056/NEJM199311253292203 Solal-Celigny et al. 1993 (GELA GELF-86)]
+
|rowspan=3|[https://doi.org/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A Cooper et al. 1980]
−
|1986-1991
+
|rowspan=3|1972-1975
−
|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+
|rowspan=3 style="background-color:#1a9851"|Phase 3 (E-switch-ic)
−
|[[#CHVP|CHVP]]
+
|1. [[#CVPP|CVPP]]
−
| style="background-color:#91cf60" |Seems to have superior OS
+
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/105/10/3817.long Deconinck et al. 2005 (GOELAMS 064)]
+
|2. [[Hodgkin_lymphoma#MOPP|MOPP]]
−
|1994-2001
+
|style="background-color:#ffffbf"|Seems not superior
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#VCAP_88|VCAP]], then HDT
 
−
| style="background-color:#fc8d59" |Seems to have inferior EFS
 
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/108/8/2540.long Sebban et al. 2006 (GELA GELF-94)]
+
|3. [[#MVPP|MVPP]]
−
|1994-2001
+
|style="background-color:#ffffbf"|Seems not superior
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#CHOP|CHOP]], then HDT
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]]  
+
*[[Lomustine (CCNU)]]
−
*[[Doxorubicin (Adriamycin)]]
+
*[[Vincristine (Oncovin)]]
−
*[[Teniposide (Vumon)]]  
+
*[[Procarbazine (Matulane)]]
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
 
*[[Prednisone (Sterapred)]]
 
*[[Prednisone (Sterapred)]]
−
====Immunotherapy====
 
−
*[[Interferon alfa-2b (Intron-A)]]
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''GELA GELF-86:''' Solal-Celigny P, Lepage E, Brousse N, Reyes F, Haioun C, Leporrier M, Peuchmaur M, Bosly A, Parlier Y, Brice P, Coiffier B, Gisselbrecht C; Groupe d'Etude des Lymphomes de l'Adulte. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. N Engl J Med. 1993 Nov 25;329(22):1608-14. [https://doi.org/10.1056/NEJM199311253292203 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8232429 PubMed]
+
# Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. [https://doi.org/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A link to original article] [https://pubmed.ncbi.nlm.nih.gov/7397630 PubMed]
−
# '''GOELAMS 064:''' Deconinck E, Foussard C, Milpied N, Bertrand P, Michenet P, Cornillet-LeFebvre P, Escoffre-Barbe M, Maisonneuve H, Delwail V, Gressin R, Legouffe E, Vilque JP, Desablens B, Jaubert J, Ramee JF, Jenabian A, Thyss A, Le Pourhiet-Le Mevel A, Travade P, Delepine R, Colombat P; GOELAMS. High-dose therapy followed by autologous purged stem-cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by GOELAMS. Blood. 2005 May 15;105(10):3817-23. Epub 2005 Feb 1. [http://www.bloodjournal.org/content/105/10/3817.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/15687232 PubMed] NCT00696735
+
==COPP/ABVD {{#subobject:92a2c8|Regimen=1}}==
−
##'''Update:''' Gyan E, Foussard C, Bertrand P, Michenet P, Le Gouill S, Berthou C, Maisonneuve H, Delwail V, Gressin R, Quittet P, Vilque JP, Desablens B, Jaubert J, Ramée JF, Arakelyan N, Thyss A, Moluçon-Chabrot C, Delépine R, Milpied N, Colombat P, Deconinck E; Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang (GOELAMS). High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years. Blood. 2009 Jan 29;113(5):995-1001. Epub 2008 Oct 27. [https://doi.org/10.1182/blood-2008-05-160200 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18955565/ PubMed]
+
COPP/ABVD: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine
−
# '''GELA GELF-94:''' Sebban C, Mounier N, Brousse N, Belanger C, Brice P, Haioun C, Tilly H, Feugier P, Bouabdallah R, Doyen C, Salles G, Coiffier B. Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA). Blood. 2006 Oct 15;108(8):2540-4. Epub 2006 Jul 11. [http://www.bloodjournal.org/content/108/8/2540.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/16835383 PubMed] NCT00140569
+
<br>C-MOPP/ABVD: '''<u>C</u>'''yclophospha'''<u>M</u>'''ide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine
−
==COPA {{#subobject:5d3856|Regimen=1}}==
 
−
COPA: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:2a4d8d|Variant=1}}===
+
===Protocol variant #1, 4 cycles {{#subobject:771e81|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 261: Line 247:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1200/JCO.1987.5.9.1329 O'Connell et al. 1987]
+
|[https://doi.org/10.1200/JCO.2002.20.2.476 Sieber et al. 2002 (GHSG HD5)]
−
|1978-1983
+
|1988-1993
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|1. [[#COPA-B_88|COPA-B]]<br>2. [[#CAP-BOP_88|CAP-BOP]]
+
|[[#COPP.2FABV.2FIMEP_99|COPP/ABV/IMEP]]
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
+
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
−
|[https://doi.org/10.1056/NEJM199211053271902 Smalley et al. 1992]
+
|[https://doi.org/10.1093/annonc/mdh046 Sieber et al. 2004 (GHSG HD6)]
−
|1985-1988
+
|1988-1993
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#I-COPA_88|I-COPA]]
+
|[[#COPP.2FABV.2FIMEP_99|COPP/ABV/IMEP]]
−
| style="background-color:#d73027" |Inferior TTTF
+
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://doi.org/10.1200/JCO.2003.03.023 Engert et al. 2003 (GHSG HD8)]
 +
|1993-1998
 +
|style="background-color:#91cf61"|Non-randomized portion of RCT
 +
|style="background-color:#d3d3d3"|
 +
|style="background-color:#d3d3d3"|
 
|-
 
|-
 
|}
 
|}
−
''Note: this regimen is very similar but distinct from CHOP. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
+
====Chemotherapy, COPP portion====
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]]
−
*[[Vincristine (Oncovin)]] 1.2 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Vincristine (Oncovin)]]
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Procarbazine (Matulane)]]
−
====Glucocorticoid therapy====
+
====Glucocorticoid therapy, COPP portion====
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
*[[Prednisone (Sterapred)]]
−
'''28-day cycle for 8 cycles'''
+
'''28-day cycle for 2 total cycles of COPP, alternating with 2 total cycles of ABVD'''
−
</div></div>
+
====Chemotherapy, ABVD portion====
−
===References===
+
*[[Doxorubicin (Adriamycin)]]
−
# O'Connell MJ, Harrington DP, Earle JD, Johnson GJ, Glick JH, Carbone PP, Creech RH, Neiman RS, Mann RB, Silverstein MN. Prospectively randomized clinical trial of three intensive chemotherapy regimens for the treatment of advanced unfavorable histology non-Hodgkin's lymphoma. J Clin Oncol. 1987 Sep;5(9):1329-39. [https://doi.org/10.1200/JCO.1987.5.9.1329 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2442322 PubMed]
+
*[[Bleomycin (Blenoxane)]]
−
# Smalley RV, Andersen JW, Hawkins MJ, Bhide V, O'Connell MJ, Oken MM, Borden EC. Interferon alfa combined with cytotoxic chemotherapy for patients with non-Hodgkin's lymphoma. N Engl J Med. 1992 Nov 5;327(19):1336-41. [https://doi.org/10.1056/NEJM199211053271902 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1406835 PubMed]
+
*[[Vinblastine (Velban)]]
−
==CVP {{#subobject:85625d|Regimen=1}}==
+
*[[Dacarbazine (DTIC)]]
−
CVP: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
+
'''28-day cycle for 2 total cycles of ABVD, alternating with 2 total cycles of COPP'''
−
<br>COP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
+
</div>
−
<br>VCP: '''<u>V</u>'''incristine, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone
+
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*GHSG HD5 & HD6: [[Hodgkin_lymphoma#Radiation_therapy_2|EFRT]]
 +
*GHSG HD8: [[Hodgkin_lymphoma#Radiation_therapy_2|EFRT]] versus [[Hodgkin_lymphoma#Radiation_therapy_2|IFRT]]
 +
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 750/1.4/40 {{#subobject:dfc019|Variant=1}}===
+
===Protocol variant #2, 6 cycles {{#subobject:6d7f98|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"
−
!style="width: 17%"|Study
+
!style="width: 25%"|Study
−
!style="width: 15%"|Years of enrollment
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!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/10.1200/JCO.2005.03.7952 Hagenbeek et al. 2006]
+
|[https://doi.org/10.1093/oxfordjournals.annonc.a059357 Diehl et al. 1995 (GHSG HD3)]
−
|1993-1997
+
|style="background-color:#91cf61"|Non-randomized portion of RCT
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[#Fludarabine_monotherapy|Fludarabine]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS48
 
−
| style="background-color:#1a9850" |Less toxic
 
−
|-
 
−
|[http://www.bloodjournal.org/content/105/4/1417.full Marcus et al. 2004]
 
−
|2000-2002
 
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Follicular_lymphoma#R-CVP|R-CVP]]
 
−
|style="background-color:#d73027"|Inferior TTP
 
−
|style="background-color:#91cf61"|Similar toxicity
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
+
====Chemotherapy, COPP portion====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Vincristine (Oncovin)]]
−
====Glucocorticoid therapy====
+
*[[Procarbazine (Matulane)]]
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
====Glucocorticoid therapy, COPP portion====
−
'''21-day cycle for up to 8 cycles'''
+
*[[Prednisone (Sterapred)]]
 +
'''28-day cycle for 3 total cycles of COPP, alternating with 3 total cycles of ABVD'''
 +
====Chemotherapy, ABVD portion====
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Bleomycin (Blenoxane)]]
 +
*[[Vinblastine (Velban)]]
 +
*[[Dacarbazine (DTIC)]]
 +
'''28-day cycle for 3 total cycles of ABVD, alternating with 3 total cycles of COPP'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*COPP/ABVD x 1 (8 cycles total) versus IFRT
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, 1000/1.4/100 {{#subobject:cb6f9b|Variant=1}}===
+
===Protocol variant #3, 10 cycles {{#subobject:faa63|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 333: Line 324:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ Hochster et al. 2009 (ECOG E1496)]
+
|[https://jjco.oxfordjournals.org/content/30/3/146.long Takenaka et al. 2000 (JCOG 8905)]
−
|NR
+
|1989-1993
 +
|style="background-color:#91cf61"|Phase 2
 +
|style="background-color:#d3d3d3"|
 +
|style="background-color:#d3d3d3"|
 +
|-
 +
|[https://doi.org/10.1200/jco.1998.16.12.3810 Diehl et al. 1998 (GHSG HD9)]
 +
|1993-1998
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|1. [[Hodgkin_lymphoma#BEACOPP_2|BEACOPP]]<br>2. [[Hodgkin_lymphoma#eBEACOPP_2|eBEACOPP]]
 +
|style="background-color:#fc8d59"|Seems to have inferior OS
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdi023 Ballova et al. 2005 (GHSG HD9elderly)]
 +
|1993-1998
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#FC|FC]]
+
|[[Hodgkin_lymphoma#BEACOPP_2|BEACOPP]]
−
|style="background-color:#d3d3d3"|Not reported
+
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
 
|}
 
|}
−
''Note: the FC arm was closed prematurely and comparisons between CVP and FC were not conducted.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
+
====Chemotherapy, COPP portion====
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
+
*[[Cyclophosphamide (Cytoxan)]] as follows:
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
**Cycles 1, 3, 5, 7, 9: 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
−
====Glucocorticoid therapy====
+
*[[Vincristine (Oncovin)]] as follows:
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
**Cycles 1, 3, 5, 7, 9: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
−
'''21-day cycle for 6 to 8 cycles'''
+
*[[Procarbazine (Matulane)]] as follows:
 +
**Cycles 1, 3, 5, 7, 9: 100 mg/m<sup>2</sup> (maximum dose of 150 mg) PO once per day on days 1 to 14
 +
====Glucocorticoid therapy, COPP portion====
 +
*[[Prednisone (Sterapred)]] as follows:
 +
**Cycles 1, 3, 5, 7, 9: 40 mg/m<sup>2</sup> PO once per day on days 1 to 3, 8 to 10
 +
====Chemotherapy, ABVD portion====
 +
*[[Doxorubicin (Adriamycin)]] as follows:
 +
**Cycles 2, 4, 6, 8, 10: 25 mg/m<sup>2</sup> IV once per day on days 1 & 15
 +
*[[Bleomycin (Blenoxane)]] as follows:
 +
**Cycles 2, 4, 6, 8, 10: 9 mg/m<sup>2</sup> (maximum dose of 15 mg) IV once per day on days 1 & 15
 +
*[[Vinblastine (Velban)]] as follows:
 +
**Cycles 2, 4, 6, 8, 10: 6 mg/m<sup>2</sup> (maximum dose of 10 mg) IV once per day on days 1 & 15
 +
*[[Dacarbazine (DTIC)]] as follows:
 +
**Cycles 2, 4, 6, 8, 10: 250 mg/m<sup>2</sup> IV once per day on days 1 & 15
 +
'''28-day cycle for 10 cycles'''
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#cbd5e7">
 
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*[[Follicular_lymphoma#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance versus [[Follicular_lymphoma#Observation_2|observation]]
+
*Some studies: [[Hodgkin_lymphoma#Radiation_therapy_2|IFRT]] x 30 Gy after completion of chemotherapy was given to patients with bulky (at least 10 cm maximum diameter) disease
−
</div></div><br>
+
====Dose modifications====
 +
*Treatment was postponed for at least 1 week or until recovery if:
 +
**Pretreatment ANC was less than 1500/uL
 +
**Platelet count was less than 100 x 10<sup>9</sup>/L
 +
**AST/S-GOT was greater than 100 IU/L
 +
**Total bilirubin was greater than 2
 +
*Vincristine and vinblastine were temporarily discontinued if patients had grade 2 or greater neurotoxicity (e.g. motor weakness, paresthesia, constipation)
 +
*Doxorubicin was discontinued if cardiac LV ejection fraction was less than 50%
 +
*Bleomycin was stopped if the PaO2 was less than 70 mmHg or if it decreased more than 10 mmHg from the previous measurement
 +
*Note: Dacarbazine 250 mg/m<sup>2</sup> was used at this dose reduction based on experiences in a pilot study in which there was severe emesis with 375 mg/m<sup>2</sup>.
 +
</div></div>
 +
===References===
 +
# '''GHSG HD3:''' Diehl V, Loeffler M, Pfreundschuh M, Ruehl U, Hasenclever D, Nisters-Backes H, Sieber M, Smith K, Tesch H, Geilen W, Adler M, Bartels H, Brandenburg U, Diezler P, Doelken G, Enzian J, Fuchs R, Gassmann W, Gerhartz H, Hagenaukamp U, Hecht T, Hiller E, Hinkelbein H, Lathan B, Kirchner H, Kuehn G, Kuerten H, Loos U, Makoski B, Oertel W, Petsch S, Pfab R, Pflueger H, Planker M, Rohioff R, Sack H, Samandari S, Sauer R, Schalk K, Schmitz G, Schoppe W, Schwieder G, Szepesi S, Teichmann J, Wilhelmy W, Worst P, Fischer R, Georgii A, Huebner E, Schwarze EW; German Hodgkin's Study Group. Further chemotherapy versus low-dose involved-field radiotherapy as consolidation of complete remission after six cycles of alternating chemotherapy in patients with advance Hodgkin's disease. Ann Oncol. 1995 Nov;6(9):901-10. [https://doi.org/10.1093/oxfordjournals.annonc.a059357 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8624293 PubMed]
 +
# '''GHSG HD9:''' Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Rueffer JU, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duehmke E, Georgii A, Loeffler M. BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 1998 Dec;16(12):3810-21. [https://doi.org/10.1200/jco.1998.16.12.3810 link to original article]'''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9850026 PubMed]
 +
## '''Update:''' Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dörken B, Müller-Hermelink HK, Dühmke E, Loeffler M; German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12;348(24):2386-95. [https://doi.org/10.1056/NEJMoa022473 link to original article]'''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12802024 PubMed]
 +
## '''Update:''' Engert A, Diehl V, Franklin J, Lohri A, Dörken B, Ludwig WD, Koch P, Hänel M, Pfreundschuh M, Wilhelm M, Trümper L, Aulitzky WE, Bentz M, Rummel M, Sezer O, Müller-Hermelink HK, Hasenclever D, Löffler M. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009 Sep 20;27(27):4548-54. [https://doi.org/10.1200/jco.2008.19.8820 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19704068 PubMed]
 +
## '''Pooled update:''' von Tresckow B, Kreissl S, Dipl-Math HG, Bröckelmann PJ, Pabst T, Fridrik M, Rummel M, Jung W, Thiemer J, Sasse S, Bürkle C, Baues C, Diehl V, Engert A, Borchmann P; German Hodgkin Study Group. Intensive treatment strategies in advanced-stage Hodgkin's lymphoma (HD9 and HD12): analysis of long-term survival in two randomised trials. Lancet Haematol. 2018 Oct 01;5(10):e462-73. [https://doi.org/10.1016/S2352-3026(18)30140-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30290903 PubMed]
 +
# '''JCOG 8905:''' Takenaka T, Mikuni C, Miura A, Sasaki T, Suzuki H, Hotta T, Hirano M, Fukuhara S, Sugiyama H, Nasu K, Dohi H, Kozuru M, Tomonaga M, Tajima K, Niimi M, Fukuda H, Mukai K, Shimoyama M; Lymphoma Study Group of the Japan Clinical Oncology Group. Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). Jpn J Clin Oncol. 2000 Mar;30(3):146-52. [https://jjco.oxfordjournals.org/content/30/3/146.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10798542 PubMed]
 +
# '''GHSG HD5:''' Sieber M, Tesch H, Pfistner B, Rueffer U, Lathan B, Brosteanu O, Paulus U, Koch T, Pfreundschuh M, Loeffler M, Engert A, Josting A, Wolf J, Hasenclever D, Franklin J, Duehmke E, Georgii A, Schalk KP, Kirchner H, Doelken G, Munker R, Koch P, Herrmann R, Greil R, Anselmo AP, Diehl V. Rapidly alternating COPP/ABV/IMEP is not superior to conventional alternating COPP/ABVD in combination with extended-field radiotherapy in intermediate-stage Hodgkin's lymphoma: final results of the German Hodgkin's Lymphoma Study Group Trial HD5. J Clin Oncol. 2002 Jan 15;20(2):476-84. [https://doi.org/10.1200/JCO.2002.20.2.476 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11786577 PubMed]
 +
# '''GHSG HD8:''' Engert A, Schiller P, Josting A, Herrmann R, Koch P, Sieber M, Boissevain F, De Wit M, Mezger J, Duhmke E, Willich N, Muller RP, Schmidt BF, Renner H, Muller-Hermelink HK, Pfistner B, Wolf J, Hasenclever D, Loffler M, Diehl V; German Hodgkin's Lymphoma Study Group. Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2003 Oct 1;21(19):3601-8. Epub 2003 Aug 11. [https://doi.org/10.1200/JCO.2003.03.023 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12913100 PubMed]
 +
## '''Update:''' Sasse S, Klimm B, Görgen H, Fuchs M, Heyden-Honerkamp A, Lohri A, Koch O, Wilhelm M, Trenn G, Finke J, Müller RP, Diehl V, Eich HT, Borchmann P, Engert A; German Hodgkin Study Group (GHSG). Comparing long-term toxicity and efficacy of combined modality treatment including extended- or involved-field radiotherapy in early-stage Hodgkin's lymphoma. Ann Oncol. 2012 Nov;23(11):2953-9. Epub 2012 Jul 5. [https://doi.org/10.1093/annonc/mds110 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22767583 PubMed]
 +
## '''Update:''' Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, Buerkle C, Borchmann S, Fuchs M, Borchmann P, Diehl V, Engert A. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017 Jun 20;35(18):1999-2007. Epub 2017 Apr 18. [https://doi.org/10.1200/JCO.2016.70.9410 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28418763 PubMed]
 +
# '''GHSG HD6:''' Sieber M, Tesch H, Pfistner B, Rueffer U, Paulus U, Munker R, Hermann R, Doelken G, Koch P, Oertel J, Roller S, Worst P, Bischof H, Glunz A, Greil R, von Kalle K, Schalk KP, Hasenclever D, Brosteanu O, Duehmke E, Georgii A, Engert A, Loeffler M, Diehl V, Mueller RP, Willich N, Fischer R, Hansmann ML, Stein H, Schober T, Koch B; German Hodgkin's Lymphoma Study Group. Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial. Ann Oncol. 2004 Feb;15(2):276-82. [https://doi.org/10.1093/annonc/mdh046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14760122 PubMed]
 +
# '''GHSG HD9elderly:''' Ballova V, Rüffer JU, Haverkamp H, Pfistner B, Müller-Hermelink HK, Dühmke E, Worst P, Wilhelmy M, Naumann R, Hentrich M, Eich HT, Josting A, Löffler M, Diehl V, Engert A. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005 Jan;16(1):124-31. [https://doi.org/10.1093/annonc/mdi023 link to original article]'''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15598949 PubMed]
 +
==CVPP {{#subobject:be8f99|Regimen=1}}==
 +
CVPP: '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''inblastine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #3, 2000/1.4/100 {{#subobject:24f33f|Variant=1}}===
+
===Regimen {{#subobject:e71c98|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 362: Line 403:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://pubmed.ncbi.nlm.nih.gov/8656680 Unterhalt et al. 1996]
+
|rowspan=3|[https://doi.org/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A Cooper et al. 1980]
−
|NR in abstract
+
|rowspan=3|1972-1975
−
|style="background-color:#1a9851"|Phase 3 (C)
+
|rowspan=3 style="background-color:#1a9851"|Phase 3 (E-switch-ic)
−
|[[#PmM_88|PmM]]
+
|1. [[#COPP_.28CCNU.29|COPP]]
−
| style="background-color:#fc8d59" |Seems to have inferior EFS
+
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|2. [[Hodgkin_lymphoma#MOPP|MOPP]]
 +
|style="background-color:#91cf60"|Seems to have superior CR rate
 +
|-
 +
|3. [[#MVPP|MVPP]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://academic.oup.com/jnci/article-abstract/80/18/1466/943469 Pavlovsky et al. 1988]
 +
|1977-1986
 +
|style="background-color:#1a9851"|Randomized (E-de-esc)
 +
|[[#CVPP_.26_88|CVPP & RT]]
 +
| style="background-color:#d73027" |Inferior FFS<sup>1</sup>
 +
|-
 +
|[https://doi.org/10.1200/JCO.1997.15.7.2652 Pavlovsky et al. 1997]
 +
|1986-NR
 +
|style="background-color:#1a9851"|Randomized (C)
 +
|[[#AOPE_99|AOPE]]
 +
|style="background-color:#91cf60"|Seems to have superior CR rate
 +
|-
 +
|[https://doi.org/10.1002/(SICI)1096-911X(199712)29:6%3C544::AID-MPO5%3E3.0.CO;2-K Sackmann-Muriel et al. 1997]
 +
|1987-1994
 +
|style="background-color:#1a9851"|Randomized (C)
 +
|[[#AOPE_99|AOPE]]
 +
|style="background-color:#91cf60"|Seems to have superior EFS
 
|-
 
|-
 
|}
 
|}
 +
''<sup>1</sup>No advantage was seen for either arm in the favorable prognosis group, whereas this arm had inferior DFS for the unfavorable prognosis group.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 5
+
*[[Lomustine (CCNU)]]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
+
*[[Vinblastine (Velban)]]
 +
*[[Procarbazine (Matulane)]]
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 5
+
*[[Prednisone (Sterapred)]]
−
'''21-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders: [[#CVP|COP]] x 2 (8 total), then [[#Interferon_alfa-2a_monotherapy|interferon alfa]] maintenance versus [[Follicular_lymphoma#Observation_2|observation]]
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Unterhalt M, Herrmann R, Tiemann M, Parwaresch R, Stein H, Trümper L, Nahler M, Reuss-Borst M, Tirier C, Neubauer A, Freund M, Kreuser ED, Dietzfelbinger H, Bodenstein H, Engert A, Stauder R, Eimermacher H, Landys K, Hiddemann W; German Low-Grade Lymphoma Study Group. Prednimustine, mitoxantrone (PmM) vs cyclophosphamide, vincristine, prednisone (COP) for the treatment of advanced low-grade non-Hodgkin's lymphoma. Leukemia. 1996 May;10(5):836-43. [https://pubmed.ncbi.nlm.nih.gov/8656680 PubMed]
+
# Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. [https://doi.org/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A link to original article] [https://pubmed.ncbi.nlm.nih.gov/7397630 PubMed]
−
## '''Update:''' Hiddemann W, Unterhalt M, Herrmann R, Wöltjen HH, Kreuser ED, Trümper L, Reuss-Borst M, Terhardt-Kasten E, Busch M, Neubauer A, Kaiser U, Hanrath RD, Middeke H, Helm G, Freund M, Stein H, Tiemann M, Parwaresch R. Mantle-cell lymphomas have more widespread disease and a slower response to chemotherapy compared with follicle-center lymphomas: results of a prospective comparative analysis of the German Low-Grade Lymphoma Study Group. J Clin Oncol. 1998 May;16(5):1922-30. [https://doi.org/10.1200/JCO.1998.16.5.1922 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9586911 PubMed]
+
# Pavlovsky S, Maschio M, Santarelli MT, Sackmann Muriel F, Corrado C, Garcia I, Schwartz L, Montero C, Lobo Sanahuja F, Magnasco O, Raha R, Cavagnaro F. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage I-II Hodgkin's disease. J Natl Cancer Inst. 1988 Nov 16;80(18):1466-73. [https://academic.oup.com/jnci/article-abstract/80/18/1466/943469 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3184196 PubMed]
−
# Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. Epub 2004 Oct 19.[http://www.bloodjournal.org/content/105/4/1417.full link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15494430 PubMed]
+
## '''Update:''' Pavlovsky S, Santarelli MT, Sackmann Muriel F, Fernández I, Garcia I, Schwartz L, Montero C, Sanahuja FL, Magnasco H, Costa A, Corrado C, Raha R, Bezares R. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage III-IV A & B Hodgkin's disease. Ann Oncol. 1992 Jul;3(7):533-7. [https://doi.org/10.1093/oxfordjournals.annonc.a058255 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1498073 PubMed]
−
## '''Update:''' Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, Offner FC, Gomez-Codina J, Belch A, Cunningham D, Wassner-Fritsch E, Stein G. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008 Oct 1;26(28):4579-86. Epub 2008 Jul 28. [https://doi.org/10.1200/jco.2007.13.5376 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18662969 PubMed]
+
# Pavlovsky S, Schvartzman E, Lastiri F, Magnasco H, Corrado C, Raslawski E, Cancela ME, Ardaiz MC, Cerutti I, Rosso A, Bruno S, Aranguren PN, Salvarezza A, Donato H, Dibar E, Zirone S; GATLA. Randomized trial of CVPP for three versus six cycles in favorable-prognosis and CVPP versus AOPE plus radiotherapy in intermediate-prognosis untreated Hodgkin's disease. J Clin Oncol. 1997 Jul;15(7):2652-8. [https://doi.org/10.1200/JCO.1997.15.7.2652 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9215837 PubMed]
−
# Hagenbeek A, Eghbali H, Monfardini S, Vitolo U, Hoskin PJ, de Wolf-Peeters C, MacLennan K, Staab-Renner E, Kalmus J, Schott A, Teodorovic I, Negrouk A, van Glabbeke M, Marcus R. Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage III and IV low-grade malignant Non-Hodgkin's lymphoma. J Clin Oncol. 2006 Apr 1;24(10):1590-6. [https://doi.org/10.1200/JCO.2005.03.7952 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16575010 PubMed]
+
# Sackmann-Muriel F, Zubizarreta P, Gallo G, Scopinaro M, Alderete D, Alfaro E, Casak S, Chantada G, Felice MS, Quinteros R. Hodgkin disease in children: results of a prospective randomized trial in a single institution in Argentina. Med Pediatr Oncol. 1997 Dec;29(6):544-52. [https://doi.org/10.1002/(SICI)1096-911X(199712)29:6%3C544::AID-MPO5%3E3.0.CO;2-K link to original article] [https://pubmed.ncbi.nlm.nih.gov/9324342 PubMed]
−
<!-- Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL, and the Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL. -->
+
==Doxorubicin & Vinblastine {{#subobject:66828f|Regimen=1}}==
−
# '''ECOG E1496:''' Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [https://doi.org/10.1200/jco.2008.17.1561 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19255334 PubMed] NCT00003204
 
−
## '''Update:''' Barta SK, Li H, Hochster HS, Hong F, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Colocci N, Bengtson EM, Horning SJ, Kahl BS. Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496). Cancer. 2016 Oct;122(19):2996-3004. Epub 2016 Jun 28. [https://doi.org/10.1002/cncr.30137 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030179/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27351685 PubMed]
 
−
==CVP, then <sup>131</sup>Iodine-Tositumomab {{#subobject:60e420|Regimen=1}}==
 
−
CVP-RIT: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone, then '''<u>R</u>'''adio'''<u>I</u>'''mmuno'''<u>T</u>'''herapy
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:1e9d16|Variant=1}}===
+
===Regimen {{#subobject:597e32|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!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.2009.27.8325 Link et al. 2010]
+
|[https://doi.org/10.1200/JCO.2001.19.22.4238 Press et al. 2001 (SWOG S9133)]
−
|style="background-color:#91cf61"|Phase 2
+
|1992-2000
 +
|style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|[[#Radiation_therapy_88|STLI]]
 +
| style="background-color:#1a9850" |Superior PFS
 
|-
 
|-
 
|}
 
|}
 +
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy, CVP portion====
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV once per day on days 1 & 15
−
====Glucocorticoid therapy, CVP portion====
+
'''28-day cycle for 3 cycles'''
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
</div>
−
'''21-day cycle for 6 cycles, followed within 56 days by:'''  
+
<div class="toccolours" style="background-color:#cbd5e7">
−
====Radioconjugate therapy, dosimetric step====
+
====Subsequent treatment====
−
*On Day 1, infusions of:
+
*STLI
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
 
−
**First scan of whole body dosimetry & redistribution within 1 hour of finishing dosimetric dose on day 1
 
−
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 
−
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO three times per day, Lugol solution 20 drops PO three times per day, or potassium iodide tablets 130 mg PO once per day, starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion
 
−
====Radioconjugate therapy, therapeutic step====
 
−
*Any one day 7 to 14 days after dosimetric infusion, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour, given first
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 
−
***65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3
 
−
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*Potassium iodide (SSKI, saturated solution of potassium iodide) 4 drops PO three times per day, Lugol solution 20 drops PO three times per day, or potassium iodide tablets 130 mg PO once per day, starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Link BK, Martin P, Kaminski MS, Goldsmith SJ, Coleman M, Leonard JP. Cyclophosphamide, vincristine, and prednisone followed by tositumomab and iodine-131-tositumomab in patients with untreated low-grade follicular lymphoma: eight-year follow-up of a multicenter phase II study. J Clin Oncol. 2010 Jun 20;28(18):3035-41. Epub 2010 May 10. [https://doi.org/10.1200/jco.2009.27.8325 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20458031 PubMed].
+
# '''SWOG S9133:''' Press OW, LeBlanc M, Lichter AS, Grogan TM, Unger JM, Wasserman TH, Gaynor ER, Peterson BA, Miller TP, Fisher RI. Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease. J Clin Oncol. 2001 Nov 15;19(22):4238-44. [https://doi.org/10.1200/JCO.2001.19.22.4238 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11709567 PubMed] NCT00002495
−
==Fludarabine monotherapy {{#subobject:227afa|Regimen=1}}==
+
==LOPP {{#subobject:f2a168|Regimen=1}}==
 +
LOPP: '''<u>L</u>'''eukeran (Chlorambucil), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:0332ee|Variant=1}}===
+
===Regimen {{#subobject:bfcf5a|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 443: Line 490:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1200/JCO.2000.18.4.773 Zinzani et al. 2000]
+
|[https://doi.org/10.1016/s0167-8140(86)80032-9 Hancock 1986]
−
|1995-1998
+
|1979-NR
−
| style="background-color:#1a9851" |Phase 3 (C)
+
| style="background-color:#1a9851" |Randomized (E-switch-ic)
−
|[[#Fludarabine_.26_Idarubicin_99|Fludarabine & Idarubicin]]
+
|[[Hodgkin_lymphoma#MOPP|MOPP]]
−
| style="background-color:#1a9850" |Superior CR rate<sup>1</sup>
+
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|[https://doi.org/10.1200/JCO.1992.10.8.1252 Hancock et al. 1992]
 +
|1983-1989
 +
| style="background-color:#1a9851" |Randomized (C)
 +
|[[#LOPP.2FEVAP|LOPP/EVAP]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>The superiority of this arm was only observed in the FL subgroup; overall, there was no statistically significant difference between arms.''<br>
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]]
+
*[[Chlorambucil (Leukeran)]]
 +
*[[Vincristine (Oncovin)]]
 +
*[[Procarbazine (Matulane)]]
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Zinzani PL, Magagnoli M, Moretti L, De Renzo A, Battista R, Zaccaria A, Guardigni L, Mazza P, Marra R, Ronconi F, Lauta VM, Bendandi M, Gherlinzoni F, Gentilini P, Ciccone F, Cellini C, Stefoni V, Ricciuti F, Gobbi M, Tura S. Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma. J Clin Oncol. 2000 Feb;18(4):773-9. [https://doi.org/10.1200/JCO.2000.18.4.773 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10673518 PubMed]
+
# Hancock BW; British National Lymphoma Investigation. Randomised study of MOPP (mustine, Oncovin, procarbazine, prednisone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease. Radiother Oncol. 1986 Nov;7(3):215-21. [https://doi.org/10.1016/s0167-8140(86)80032-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3544084 PubMed]
−
==FC {{#subobject:9f1357|Regimen=1}}==
+
## '''Update:''' Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Haybittle JL, Bennett MH, MacLennan KA, Jelliffe AM; BNLI. British National Lymphoma Investigation randomised study of MOPP (mustine, Oncovin, procarbazine, prednisolone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease--long term results. Br J Cancer. 1991 Apr;63(4):579-82. [https://doi.org/10.1038/bjc.1991.134 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1972355/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/2021542 PubMed]
−
FC: '''<u>F</u>'''ludarabine & '''<u>C</u>'''yclophosphamide
+
# Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Bennett MH, MacLennan KA, Haybittle JL, Anderson L, Linch DC; BNLI. LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial. J Clin Oncol. 1992 Aug;10(8):1252-8. [https://doi.org/10.1200/JCO.1992.10.8.1252 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1634914 PubMed]
−
<br>CF: '''<u>C</u>'''yclophosphamide & '''<u>F</u>'''ludarabine
+
==LOPP/EVAP {{#subobject:22b023|Regimen=1}}==
 +
LOPP/EVAP: '''<u>L</u>'''eukeran (Chlorambucil), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>E</u>'''toposide, '''<u>V</u>'''inblastine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>P</u>'''rednisone
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:5b37b5|Variant=1}}===
+
===Protocol {{#subobject:53f4da|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 470: Line 526:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668968/ Hochster et al. 2009 (ECOG E1496)]
+
|[https://doi.org/10.1200/JCO.1992.10.8.1252 Hancock et al. 1992]
−
|NR
+
|1983-1989
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+
| style="background-color:#1a9851" |Randomized (E-switch-ic)
−
|[[#CVP|CVP]]
+
|[[#LOPP|LOPP]]
−
|style="background-color:#d3d3d3"|Not reported
+
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|[https://doi.org/10.1093/annonc/5.suppl_2.s117 Hancock et al. 1994]
 +
|1990-1991
 +
| style="background-color:#1a9851" |Randomized (C)
 +
|[[#LOPP-EVA_99|LOPP-EVA]]
 +
| style="background-color:#1a9850" |Superior CR rate
 
|-
 
|-
 
|}
 
|}
−
''Note: investigation into this regimen was halted due to excess mortality.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
+
====Chemotherapy, LOPP portion====
−
*[[Fludarabine (Fludara)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
+
*[[Chlorambucil (Leukeran)]]
−
*[[Cyclophosphamide (Cytoxan)]] 1000 mg/m<sup>2</sup> IV once on day 1
+
*[[Vincristine (Oncovin)]]
−
'''28-day cycle up to 8 cycles'''
+
*[[Procarbazine (Matulane)]]
−
</div>
+
====Glucocorticoid therapy, LOPP portion====
−
<div class="toccolours" style="background-color:#cbd5e7">
+
*[[Prednisone (Sterapred)]]
−
====Subsequent treatment====
+
====Chemotherapy, EVAP portion====
−
*[[Follicular_lymphoma#Rituximab_monotherapy.2C_extended_course|Rituximab]] maintenance versus [[Follicular_lymphoma#Observation_2|observation]]
+
*[[Etoposide (Vepesid)]]
 +
*[[Vinblastine (Velban)]]
 +
*[[Doxorubicin (Adriamycin)]]
 +
====Glucocorticoid therapy, EVAP portion====
 +
*[[Prednisone (Sterapred)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL, and the Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL. -->
+
# Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Bennett MH, MacLennan KA, Haybittle JL, Anderson L, Linch DC; BNLI. LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial. J Clin Oncol. 1992 Aug;10(8):1252-8. [https://doi.org/10.1200/JCO.1992.10.8.1252 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1634914 PubMed]
−
# '''ECOG E1496:''' Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, Zhang L, Colocci N, Frankel S, Horning SJ. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol. 2009 Apr 1;27(10):1607-14. Epub 2009 Mar 2. [https://doi.org/10.1200/jco.2008.17.1561 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19255334 PubMed]
+
# Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Linch DC, Anderson L, MacLennan KA; BNLI. Hybrid LOPP/EVA is not better than LOPP alternating with EVAP: a prematurely terminated British National Lymphoma Investigation randomized trial. Ann Oncol. 1994;5 Suppl 2:117-20. [https://doi.org/10.1093/annonc/5.suppl_2.s117 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8204511 PubMed]
−
==Fludarabine, then <sup>131</sup>Iodine-Tositumomab {{#subobject:d9d902|Regimen=1}}==
+
==Mechlorethamine monotherapy {{#subobject:3674c2|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:0e2b27|Variant=1}}===
+
===Regimen {{#subobject:2761c1|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!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://jamanetwork.com/journals/jama/fullarticle/288442 Goodman et al. 1946]
 +
|NR
 +
| style="background-color:#91cf61" |Non-randomized
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://jamanetwork.com/journals/jama/article-abstract/288767 Jacobson et al. 1946]
 +
|1943-1945
 +
| style="background-color:#91cf61" |Non-randomized
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://doi.org/10.7326/0003-4819-27-4-529 Wintrobe et al. 1947]
 +
|NR
 +
| style="background-color:#91cf61" |Non-randomized
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://doi.org/10.7326/0003-4819-30-2-381 Meyer & Overmiller 1949]
 +
|1946-1947
 +
| style="background-color:#91cf61" |Non-randomized
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2005.14.803 Leonard et al. 2005]
+
|[https://jamanetwork.com/journals/jama/article-abstract/337835 Jacobs et al. 1968]
−
|style="background-color:#91cf61"|Phase 2
+
|1960-1963
 +
| style="background-color:#1a9851" |Randomized (C)
 +
|[[#Cyclophosphamide_monotherapy_99|Cyclophosphamide]]
 +
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#b3e2cd">
+
''These references are of major historic interest as they are the first systemic chemotherapy trials in humans. Note that some of these early trials used nitrogen mustards other than mechlorethamine but are grouped here for simplicity.''
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 5
+
*[[Mechlorethamine (Mustargen)]]
−
'''35-day cycle for 3 cycles, followed by:'''
 
−
====Radioconjugate therapy, dosimetric step====
 
−
*On Day 0, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
 
−
**First scan of whole body dosimetry & redistribution
 
−
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 
−
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 
−
====Radioconjugate therapy, therapeutic step====
 
−
*Any day from day 7 to 14, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 
−
***65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3
 
−
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Leonard JP, Coleman M, Kostakoglu L, Chadburn A, Cesarman E, Furman RR, Schuster MW, Niesvizky R, Muss D, Fiore J, Kroll S, Tidmarsh G, Vallabhajosula S, Goldsmith SJ. Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma. J Clin Oncol. 2005 Aug 20;23(24):5696-704. [https://doi.org/10.1200/jco.2005.14.803 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16110029 PubMed]
+
# Goodman LS, Wintrobe MM, Dameshek W, Goodman MJ, Gilman A, McLennan MT. Nitrogen mustard therapy; use of methyl-bis (beta-chloroethyl) amine hydrochloride and tris (beta-chloroethyl) amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. J Am Med Assoc. 1946 Sep 21;132:126-32. [https://jamanetwork.com/journals/jama/fullarticle/288442 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20997191 PubMed]
−
==FM {{#subobject:6a2469|Regimen=1}}==
+
# Jacobson LO, Spurr CL, Guzman-Barron ES, Smith T, Lushbaugh C, Dick GF. Nitrogen mustard therapy; studies on the effect of methyl-bis (beta-chloroethyl) amine hydrochloride on neoplastic diseases and allied disorders of the hemopoietic system. J Am Med Assoc. 1946 Oct 5;132:263-71. [https://jamanetwork.com/journals/jama/article-abstract/288767 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20997209 PubMed]
−
FM: '''<u>F</u>'''ludarabine, '''<u>M</u>'''itoxantrone
+
# Wintrobe MM, Huguley CM Jr, McLennan MT, Penna de Carvalho Lima L. Nitrogen mustard as a therapeutic agent for Hodgkin's disease, lymphosarcoma and leukemia. Ann Intern Med. 1947 Oct;27(4):529-40. [https://doi.org/10.7326/0003-4819-27-4-529 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20268426 PubMed]
 +
# Meyer AH, Overmiller WC. The use of nitrogen mustard in Hodgkin's disease and lymphosarcoma. Ann Intern Med. 1949 Feb;30(2):381-6. [https://doi.org/10.7326/0003-4819-30-2-381 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18109292 PubMed]
 +
# Jacobs EM, Peters FC, Luce JK, Zippin C, Wood DA. Mechlorethamine HCl and cyclophosphamide in the treatment of Hodgkin's disease and the lymphomas. JAMA. 1968 Feb 5;203(6):392-8. [https://jamanetwork.com/journals/jama/article-abstract/337835 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4865234 PubMed]
 +
==MOPP/ABVD {{#subobject:f28468|Regimen=1}}==
 +
MOPP/ABVD: '''<u>M</u>'''ustargen (Mechlorethamine), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone alternating with '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 75/10, IV fludarabine {{#subobject:ee1449|Variant=1}}===
+
===Protocol {{#subobject:5b28f5|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 533: Line 618:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2004.07.170 Zinzani et al. 2004]
+
|[https://doi.org/10.1056/NEJM198204013061303 Santoro et al. 1982]
−
|1999-2002
+
|1974-1980
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
−
|[[#CHOP|CHOP]]
+
|[[Hodgkin_lymphoma#MOPP|MOPP]]
−
| style="background-color:#1a9850" |Superior CR rate
+
| style="background-color:#1a9850" |Superior PFS
 +
|-
 +
|[https://doi.org/10.1200/jco.1994.12.2.279 Somers et al. 1994]
 +
|1981-1986
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[Hodgkin_lymphoma#MOPP|MOPP]]
 +
| style="background-color:#91cf60" |Seems to have superior FFS
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1056/NEJM199211193272102 Canellos et al. 1992 (CALGB 8251)]
 +
|rowspan=2|1982-NR
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[Hodgkin_lymphoma#ABVD_3|ABVD]]
 +
| style="background-color:#ffffbf" |Seems not superior<sup>1</sup>
 +
|-
 +
|2. [[Hodgkin_lymphoma#MOPP|MOPP]]
 +
| style="background-color:#91cf60" |Seems to have superior EFS<sup>1</sup>
 +
|-
 +
|[https://doi.org/10.1200/jco.1996.14.5.1421 Viviani et al. 1996]
 +
|1982-1990
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#MOPP-ABVD_99|MOPP-ABVD]]
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|[https://doi.org/10.1200/jco.1997.15.4.1638 Connor et al. 1997 (NCIC-CTG HD4)]
 +
|1984-1989
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Hodgkin_lymphoma#MOPP-ABV_3|MOPP-ABV]]
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|[https://doi.org/10.1200/JCO.1998.16.3.897 Hutchinson et al. 1998 (CCG-521)]
 +
|1986-1990
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Hodgkin_lymphoma#ABVD_3|ABVD]], then [[Hodgkin_lymphoma#Radiation_therapy_2|RT]]
 +
| style="background-color:#fee08b" |Might have inferior EFS
 
|-
 
|-
 
|}
 
|}
 +
''<sup>1</sup>Reported efficacy for CALGB 8251 is based on the 2009 update.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
+
====Chemotherapy, MOPP portion====
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
+
*[[Mechlorethamine (Mustargen)]]
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 1
+
*[[Vincristine (Oncovin)]]
−
'''21-day cycle for 6 cycles'''
+
*[[Procarbazine (Matulane)]]
−
</div>
+
====Glucocorticoid therapy, MOPP portion====
−
<div class="toccolours" style="background-color:#cbd5e7">
+
*[[Prednisone (Sterapred)]]
−
====Subsequent treatment====
+
====Chemotherapy, ABVD portion====
−
*Patients with PR or CR with detectable bcl-2/IgH fusion by PCR: [[Follicular_lymphoma#Rituximab_monotherapy.2C_abbreviated_course|R]] x 4
+
*[[Doxorubicin (Adriamycin)]]
−
</div></div><br>
+
*[[Bleomycin (Blenoxane)]]
 +
*[[Vinblastine (Velban)]]
 +
*[[Dacarbazine (DTIC)]]
 +
</div></div>
 +
===References===
 +
# Santoro A, Bonadonna G, Bonfante V, Valagussa P. Alternating drug combinations in the treatment of advanced Hodgkin's disease. N Engl J Med. 1982 Apr 1;306(13):770-5. [https://doi.org/10.1056/NEJM198204013061303 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6174865 PubMed]
 +
## '''Update:''' Bonadonna G, Valagussa P, Santoro A. Alternating non-cross-resistant combination chemotherapy or MOPP in stage IV Hodgkin's disease: a report of 8-year results. Ann Intern Med. 1986 Jun;104(6):739-46. [https://doi.org/10.7326/0003-4819-104-6-739 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2422994 PubMed]
 +
# '''CALGB 8251:''' Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992 Nov 19;327(21):1478-84. [https://doi.org/10.1056/NEJM199211193272102 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1383821 PubMed]
 +
## '''Update:''' Canellos GP, Niedzwiecki D. Long-term follow-up of Hodgkin's disease trial. N Engl J Med. 2002 May 2;346(18):1417-8. [https://doi.org/10.1056/NEJM200205023461821 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11986425 PubMed]
 +
## '''Update:''' Canellos GP, Niedzwiecki D, Johnson JL. Long-term follow-up of survival in Hodgkin's lymphoma. N Engl J Med. 2009 Dec 10;361(24):2390-1. [https://doi.org/10.1056/NEJMc0906731 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20007568 PubMed]
 +
# Somers R, Carde P, Henry-Amar M, Tarayre M, Thomas J, Hagenbeek A, Monconduit M, de Pauw BE, Breed WP, Verdonck L, Burgers JMV, Eghbali H, Zittoun R; [[Study_Groups#EORTC|EORTC]]. A randomized study in stage IIIB and IV Hodgkin's disease comparing eight courses of MOPP versus an alteration of MOPP with ABVD: a European Organisation for Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie controlled clinical trial. J Clin Oncol. 1994 Feb;12(2):279-87. [https://doi.org/10.1200/jco.1994.12.2.279 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7509381 PubMed]
 +
# Viviani S, Bonadonna G, Santoro A, Bonfante V, Zanini M, Devizzi L, Soncini F, Valagussa P. Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin's disease: ten-year results. J Clin Oncol. 1996 May;14(5):1421-30. [https://doi.org/10.1200/jco.1996.14.5.1421 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8622055 PubMed]
 +
# '''NCIC-CTG HD4:''' Connors JM, Klimo P, Adams G, Burns BF, Cooper I, Meyer RM, O'Reilly SE, Pater J, Quirt I, Sadura A, Shustik C, Skillings J, Sutcliffe S, Verma S, Yoshida S, Zee B. Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group. J Clin Oncol. 1997 Apr;15(4):1638-45. Erratum in: J Clin Oncol 1997 Jul;15(7):2762. [https://doi.org/10.1200/jco.1997.15.4.1638 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9193364 PubMed]
 +
# '''CCG-521:''' Hutchinson RJ, Fryer CJ, Davis PC, Nachman J, Krailo MD, O'Brien RT, Collins RD, Whalen T, Reardon D, Trigg ME, Gilchrist GS. MOPP or radiation in addition to ABVD in the treatment of pathologically staged advanced Hodgkin's disease in children: results of the Children's Cancer Group Phase III Trial. J Clin Oncol. 1998 Mar;16(3):897-906. [https://doi.org/10.1200/JCO.1998.16.3.897 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9508171 PubMed]
 +
==MVPP {{#subobject:b01f3a|Regimen=1}}==
 +
MVPP: '''<u>M</u>'''echlorethamine, '''<u>V</u>'''inblastine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, 100/10, IV fludarabine {{#subobject:6b877b|Variant=1}}===
+
===Regimen {{#subobject:312fd8|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 559: Line 693:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1093/annonc/mdi091 Foussard et al. 2005]
+
|rowspan=3|[https://doi.org/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A Cooper et al. 1980]
−
|1995-1999
+
|rowspan=3|1972-1975
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+
|rowspan=3 style="background-color:#1a9851"|Phase 3 (E-switch-ic)
−
|[[#mini-CHVP_88|mini-CHVP]]
+
|1. [[#COPP_.28CCNU.29|COPP]]
−
| style="background-color:#1a9850" |Superior FFS
+
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
−
|}
+
|2. [[#CVPP|CVPP]]
−
<div class="toccolours" style="background-color:#b3e2cd">
+
|style="background-color:#ffffbf"|Seems not superior
−
====Chemotherapy====
 
−
*[[Fludarabine (Fludara)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#FM_88|FM]] consolidation
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 120/10, PO fludarabine {{#subobject:be3ef5|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|[https://doi.org/10.1016/S1470-2045(08)70039-1 Zinzani et al. 2008 (FLUMIZ)]
+
|3. [[Hodgkin_lymphoma#MOPP|MOPP]]
−
|style="background-color:#91cf61"|Phase 2
+
|style="background-color:#ffffbf"|Seems not superior
−
| style="background-color:#f7fcfd" |ORR: 98%
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 3
+
*[[Mechlorethamine (Mustargen)]]
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 1
+
*[[Vinblastine (Velban)]]
−
====Supportive therapy====
+
*[[Procarbazine (Matulane)]]
−
*[[Allopurinol (Zyloprim)]] 300 mg PO once per day for patients with bulky disease
+
====Glucocorticoid therapy====
−
*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] by the following criteria:
+
*[[Prednisone (Sterapred)]]
−
**Prophylaxis: None
 
−
**Grade 3 or 4 neutropenia or delayed neutropenic fever: could be given growth factors for later cycles at physician discretion
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients were restaged 4 to 6 weeks after finishing cycle 6. People with at least a partial response (PR), ANC greater than 1500/uL, platelet count greater than 100 x 10<sup>9</sup>/L, and less than 25% bone marrow involvement were eligible for [[Follicular_lymphoma#Ibritumomab_tiuxetan_protocol_2|consolidation therapy with ibritumomab tiuxetan]] 6 to 10 weeks after the end of cycle 6.
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Zinzani PL, Pulsoni A, Perrotti A, Soverini S, Zaja F, De Renzo A, Storti S, Lauta VM, Guardigni L, Gentilini P, Tucci A, Molinari AL, Gobbi M, Falini B, Fattori PP, Ciccone F, Alinari L, Martelli M, Pileri S, Tura S, Baccarani M. Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma. J Clin Oncol. 2004 Jul 1;22(13):2654-61. Epub 2004 May 24. [https://doi.org/10.1200/jco.2004.07.170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15159414 PubMed]
+
# Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. [https://doi.org/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A link to original article] [https://pubmed.ncbi.nlm.nih.gov/7397630 PubMed]
−
# Foussard C, Colombat P, Maisonneuve H, Berthou C, Gressin R, Rousselet MC, Rachieru P, Pignon B, Mahé B, Ghandour C, Desablens B, Casassus P, Lamy T, Delwail V, Deconinck E; GOELAMS. Long-term follow-up of a randomized trial of fludarabine-mitoxantrone, compared with cyclophosphamide, doxorubicin, vindesine, prednisone (CHVP), as first-line treatment of elderly patients with advanced, low-grade non-Hodgkin's lymphoma before the era of monoclonal antibodies. Ann Oncol. 2005 Mar;16(3):466-72. Epub 2005 Feb 2. [https://doi.org/10.1093/annonc/mdi091 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15695500 PubMed]
+
==NOVP {{#subobject:230457|Regimen=1}}==
−
# '''FLUMIZ:''' Zinzani PL, Tani M, Pulsoni A, Gobbi M, Perotti A, De Luca S, Fabbri A, Zaccaria A, Voso MT, Fattori P, Guardigni L, Ronconi S, Cabras MG, Rigacci L, De Renzo A, Marchi E, Stefoni V, Fina M, Pellegrini C, Musuraca G, Derenzini E, Pileri S, Fanti S, Piccaluga PP, Baccarani M. Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ). Lancet Oncol. 2008 Apr;9(4):352-8. Epub 2008 Mar 14. [https://doi.org/10.1016/S1470-2045(08)70039-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18342572 PubMed] EudraCT 2004-002211-92
+
NOVP: '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>O</u>'''ncovin (Vincristine), '''<u>V</u>'''inblastine, '''<u>P</u>'''rednisone
−
==FND {{#subobject:6b3e61|Regimen=1}}==
 
−
FND: '''<u>F</u>'''ludarabine, '''<u>N</u>'''ovantrone (Mitoxantrone), '''<u>D</u>'''examethasone
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:b32c08|Variant=1}}===
+
===Regimen {{#subobject:5bf81f|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"
 
!style="width: 25%"|Study
 
!style="width: 25%"|Study
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.1996.14.4.1262 McLaughlin et al. 1996]
+
|[https://pubmed.ncbi.nlm.nih.gov/2259922 Hagemeister et al. 1990]
 
|style="background-color:#91cf61"|Phase 2
 
|style="background-color:#91cf61"|Phase 2
 
|-
 
|-
Line 621: Line 730:
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
+
*[[Mitoxantrone (Novantrone)]]
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 1
+
*[[Vincristine (Oncovin)]]
 +
*[[Vinblastine (Velban)]]
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Dexamethasone (Decadron)]] 20 mg/day IV or PO on days 1 to 5
+
*[[Prednisone (Sterapred)]]
−
'''28-day cycle for up to 8 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# McLaughlin P, Hagemeister FB, Romaguera JE, Sarris AH, Pate O, Younes A, Swan F, Keating M, Cabanillas F. Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma. J Clin Oncol. 1996 Apr;14(4):1262-8. [https://doi.org/10.1200/jco.1996.14.4.1262 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8648382 PubMed]
+
# Hagemeister FB, Cabanillas F, Velásquez WS, Meistrich ML, Liang JC, McLaughlin P, Redman JR, Romaguera JE, Rodríguez MA, Swan F Jr, Fuller LM. NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease. Semin Oncol. 1990 Dec;17(6 Suppl 10):34-8. [https://mdanderson.elsevierpure.com/en/publications/novp-a-novel-chemotherapeutic-regimen-with-minimal-toxicity-for-t link to original article] [https://pubmed.ncbi.nlm.nih.gov/2259922 PubMed]
−
==<sup>131</sup>Iodine-Tositumomab monotherapy {{#subobject:f69726|Regimen=1}}==
+
==SCAB {{#subobject:344883|Regimen=1}}==
 +
SCAB: '''<u>S</u>'''treptozocin, '''<u>C</u>'''CNU (Lomustine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:a80cf3|Variant=1}}===
+
===Regimen {{#subobject:a68d3b|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"
 
!style="width: 25%"|Study
 
!style="width: 25%"|Study
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1056/NEJMoa041511 Kaminski et al. 2005]
+
|[https://doi.org/10.1002/1097-0142(19810115)47:2%3C224::AID-CNCR2820470203%3E3.0.CO;2-6 Diggs et al. 1981]
−
|style="background-color:#91cf61"|Phase 2
+
|style="background-color:#91cf61"|Non-randomized
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Radioconjugate therapy, dosimetric step====
+
====Chemotherapy====
−
*On Day 0, infusions of:
+
*[[Streptozocin (Zanosar)]]
−
**Tositumomab 450 mg IV over 1 hour
+
*[[Lomustine (CCNU)]]
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
+
*[[Doxorubicin (Adriamycin)]]
−
**First scan of whole body dosimetry & redistribution
+
*[[Bleomycin (Blenoxane)]]
−
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 
−
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 
−
====Radioconjugate therapy, therapeutic step====
 
−
*Any day from day 7 to 14, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 
−
***65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3
 
−
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Kaminski MS, Tuck M, Estes J, Kolstad A, Ross CW, Zasadny K, Regan D, Kison P, Fisher S, Kroll S, Wahl RL. 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med. 2005 Feb 3;352(5):441-9. [https://doi.org/10.1056/NEJMoa041511 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15689582 PubMed]
+
# Diggs CH, Wiernik PH, Sutherland JC. Treatment of advanced untreated Hodgkin's disease with SCAB--an alternative to MOPP. Cancer. 1981 Jan 15;47(2):224-8. [https://doi.org/10.1002/1097-0142(19810115)47:2%3C224::AID-CNCR2820470203%3E3.0.CO;2-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6161689 PubMed]
−
## '''Update: Abstract:''' Mark S. Kaminski, MD, Melissa Tuck, MS, Judith Estes, BSN, MSN, Arne Kolstad, MD, PhD, Charles Warren Ross, MD, Denise Regan, BS, Thierry Horner, PhD, Vanessa C. Williams, MS, Tina Vleisides, DC and Richard L. Wahl, MD. Tositumomab and Iodine I-131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma: Median 10 Year Follow-up Results. ASH 2009 abstract 3759.
+
## '''Update:''' Wiernik PH, Schiffer CA. Long-term follow-up of advanced Hodgkin's disease patients treated with a combination of streptozotocin, lomustine (CCNU), doxorubicin and bleomycin (SCAB). J Cancer Res Clin Oncol. 1988;114(1):105-7. [https://doi.org/10.1007/bf00390494 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2450876 PubMed]
−
==MCP {{#subobject:5510fa|Regimen=1}}==
+
==Vinblastine monotherapy {{#subobject:b1c2da|Regimen=1}}==
−
MCP: '''<u>M</u>'''itoxantrone, '''<u>C</u>'''hlorambucil, '''<u>P</u>'''rednisone
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:a8501b|Variant=1}}===
+
===Regimen {{#subobject:48bfd8|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
 
!style="width: 20%"|Years of enrollment
 
!style="width: 20%"|Years of enrollment
Line 669: Line 770:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1002/cncr.22093 Nickenig et al. 2006 (GLSG '96)]
+
|[https://jamanetwork.com/journals/jama/article-abstract/657749 Stutzman et al. 1966]
−
|1996-1998
+
|1963-1964
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+
|style="background-color:#1a9851"|Randomized (E-switch-ic)
−
|[[#CHOP|CHOP]]
+
|[[#Cyclophosphamide_monotherapy_88|Cyclophosphamide]]
−
|style="background-color:#fee08b"|Might have inferior CR rate
+
| style="background-color:#1a9850" |Superior ORR
 
|-
 
|-
 
|}
 
|}
−
''Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m<sup>2</sup>"; total dose per day is 9 mg/m<sup>2</sup>.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
*[[Vinblastine (Velban)]]
−
*[[Chlorambucil (Leukeran)]] 3 mg/m<sup>2</sup> PO three times per day on days 1 to 5
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 25 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''28-day cycle for 6 to 8 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''GLSG '96:''' Nickenig C, Dreyling M, Hoster E, Pfreundschuh M, Trumper L, Reiser M, Wandt H, Lengfelder E, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. Combined cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) improves response rates but not survival and has lower hematologic toxicity compared with combined mitoxantrone, chlorambucil, and prednisone (MCP) in follicular and mantle cell lymphomas: results of a prospective randomized trial of the German Low-Grade Lymphoma Study Group. Cancer. 2006 Sep 1;107(5):1014-22. [https://doi.org/10.1002/cncr.22093 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16878325 PubMed]
+
# Stutzman L, Ezdinli EZ, Stutzman MA. Vinblastine sulfate vs cyclophosphamide in the therapy for lymphoma. JAMA. 1966 Jan 17;195(3):173-8. [https://jamanetwork.com/journals/jama/article-abstract/657749 link to original article] [https://pubmed.ncbi.nlm.nih.gov/5322863 PubMed]
−
==MCP (Prednisolone) {{#subobject:5762fa|Regimen=1}}==
+
==OPPA {{#subobject:6418c0|Regimen=1}}==
−
MCP: '''<u>M</u>'''itoxantrone, '''<u>C</u>'''hlorambucil, '''<u>P</u>'''rednisolone
+
OPPA: '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone, '''<u>A</u>'''driamycin (Doxorubicin)
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:75c24e|Variant=1}}===
+
===Regimen {{#subobject:e17569|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"
−
!style="width: 20%"|Study
+
! style="width: 33%" |Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 33%" |Years of enrollment
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 33%" |[[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.2006.06.4618 Herold et al. 2007 (OSHO-39)]
+
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
−
|1998-2003
+
|2002-2005
−
|style="background-color:#1a9851"|Phase 3 (C)
+
| style="background-color:#91cf61" | Phase II
−
|[[Follicular_lymphoma#R-MCP|R-MCP]]
 
−
|style="background-color:#d73027"|Inferior OS
 
 
|-
 
|-
 
|}
 
|}
−
''Note: the chlorambucil dose is written in the reference as "3 x 3 mg/m<sup>2</sup>"; total dose per day is 9 mg/m<sup>2</sup>.''
+
''This regimen is meant for girls. Patients with early-stage disease only received the OPPA portion, see text for details.''
−
<div class="toccolours" style="background-color:#b3e2cd">
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
−
*[[Chlorambucil (Leukeran)]] 3 mg/m<sup>2</sup> PO three times per day on days 1 to 5
+
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 15
 +
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 15
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Prednisolone (Millipred)]] 25 mg/m<sup>2</sup> PO once per day on days 1 to 5
+
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 15
−
'''28-day cycle for up to 8 cycles'''
+
'''28-day cycle for 2 cycles'''
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#cbd5e7">
 
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*Patients who achieved a PR or CR: [[#Interferon_alfa-2a_monotherapy|Interferon alfa-2a]] maintenance, within 4 to 8 weeks of completion of chemotherapy
+
*Treatment group 2: [[#C-MOPP|COPP]] x 2
 +
*Treatment group 3: [[#C-MOPP|COPP]] x 4
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''OSHO-39:''' Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dölken G, Naumann R, Knauf W, Freund M, Rohrberg R, Höffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grünhagen U; East German Study Group Hematology and Oncology Study. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007 May 20;25(15):1986-92. Epub 2007 Apr 9. [https://doi.org/10.1200/jco.2006.06.4618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17420513 PubMed] NCT00269113
+
#'''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832
−
## '''Update:''' Herold M, Scholz CW, Rothmann F, Hirt C, Lakner V, Naumann R. Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma. J Cancer Res Clin Oncol. 2015 Sep;141(9):1689-95. Epub 2015 Mar 25. [http://link.springer.com/article/10.1007/s00432-015-1963-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25804839 PubMed]
+
==VAMP (Methotrexate) {{#subobject:4d666a|Regimen=1}}==
−
==ProMACE-MOPP {{#subobject:0aa31b|Regimen=1}}==
+
VAMP: '''<u>V</u>'''inblastine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>M</u>'''ethrotrexate, '''<u>P</u>'''rednisone
−
ProMACE-MOPP: '''<u>Pro</u>'''lix (Prednisone), '''<u>M</u>'''ethotrexate, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>M</u>'''ustargen (Mechlorethamine), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:cf90b9|Variant=1}}===
+
===Regimen {{#subobject:6f694d|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"
−
!style="width: 33%"|Study
+
! style="width: 25%" |Study
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 33%"|Comparator
 
 
|-
 
|-
−
|[https://pubmed.ncbi.nlm.nih.gov/2456618 Young et al. 1988]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526806/ Metzger et al. 2012 (HOD99)]
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
+
| style="background-color:#91cf61" |Phase 2
−
|[[Follicular_lymphoma#Observation|Observation]]
 
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#b3e2cd">
+
''To be completed? This is to be distinguished from the VAMP protocols used in AML and multiple myeloma.''
 
====Chemotherapy====
 
====Chemotherapy====
 +
*[[Vinblastine (Velban)]]
 +
*[[Doxorubicin (Adriamycin)]]
 
*[[Methotrexate (MTX)]]
 
*[[Methotrexate (MTX)]]
−
*[[Doxorubicin (Adriamycin)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Etoposide (Vepesid)]]
 
−
*[[Mechlorethamine (Mustargen)]]
 
−
*[[Vincristine (Oncovin)]]
 
−
*[[Procarbazine (Matulane)]]
 
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Prednisone (Sterapred)|Prednisone (Prolix)]]
 
 
*[[Prednisone (Sterapred)]]
 
*[[Prednisone (Sterapred)]]
 +
'''4 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*Early responders: [[Hodgkin_lymphoma_-_null_regimens#Observation|Observation]] versus [[#Radiation_therapy_2|RT]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Young RC, Longo DL, Glatstein E, Ihde DC, Jaffe ES, DeVita VT Jr. The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. Semin Hematol. 1988 Apr;25(2 Suppl 2):11-6. [https://pubmed.ncbi.nlm.nih.gov/2456618 PubMed]
+
#'''HOD99:''' Metzger ML, Weinstein HJ, Hudson MM, Billett AL, Larsen EC, Friedmann A, Howard SC, Donaldson SS, Krasin MJ, Kun LE, Marcus KJ, Yock TI, Tarbell N, Billups CA, Wu J, Link MP. Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma. JAMA. 2012 Jun 27;307(24):2609-16. [https://jamanetwork.com/journals/jama/fullarticle/1199151 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526806/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22735430 PubMed]
−
=Consolidation after first-line therapy=
+
==ABVE {{#subobject:c24h71|Regimen=1}}==
−
==<sup>131</sup>Iodine-Tositumomab monotherapy {{#subobject:1d80fc|Regimen=1}}==
+
ABVE: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''incristine, '''<u>E</u>'''toposide
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:9cd058|Variant=1}}===
+
===Regimen {{#subobject:7fa7ya|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"
−
!style="width: 25%"|Study
+
! style="width: 33%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 33%" |Years of enrollment
 +
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107050/ Friedberg et al. 2014 (SWOG S0433)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3468662/ Tebbi et al. 2012 (POG P9426)]
−
|style="background-color:#91cf61"|Phase 2
+
|1996-2001
 +
| style="background-color:#91cf61" |Non-randomized (see note)
 
|-
 
|-
 
|}
 
|}
−
Will be added if drug is ever returned to market.
+
''Note: this trial had a randomization to receive or not receive dexrazoxane. Labeled here as non-randomized because this drug does not have antineoplastic properties.''
−
<div class="toccolours" style="background-color:#cbd5e8">
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Preceding treatment====
+
====Chemotherapy====
−
*[[Follicular_lymphoma#R-CHOP|R-CHOP]]
+
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15
 +
*[[Bleomycin (Blenoxane)]] 10 units/m<sup>2</sup> IV once per day on days 1 & 15
 +
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 15
 +
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
 +
====Supportive therapy====
 +
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 6 to 14, then once per day on days 16 until ANC greater than 1000/uL
 +
'''28-day cycle for 2 cycles'''
 
</div>
 
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*CR: [[#Radiation_therapy_2|IFRT]] consolidation
 +
*Other than CR: [[#ABVE|ABVE]] x 2, then [[#Radiation_therapy_2|IFRT]] consolidation
 +
</div></div>
 +
===References===
 +
#'''POG P9426:''' Tebbi CK, Mendenhall NP, London WB, Williams JL, Hutchison RE, Fitzgerald TJ, de Alarcón PA, Schwartz C, Chauvenet A. Response-dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2012 Dec 15;59(7):1259-65. Epub 2012 Aug 21. [https://doi.org/10.1002/pbc.24279 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3468662/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22911615/ PubMed] NCT00002827
 +
==MOPP {{#subobject:bcde0|Regimen=1}}==
 +
MOPP: '''<u>M</u>'''echlorethamine, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, uncapped vincristine {{#subobject:ff7478|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/42/2/163.long Young et al. 1973a]
 +
|1964-NR
 +
| style="background-color:#91cf61" |Non-randomized (RT)
 +
|-
 +
|[https://doi.org/10.1002/1097-0142(197610)38:4%3C1494::AID-CNCR2820380408%3E3.0.CO;2-E Kolygin 1976]
 +
|1970-1975
 +
| style="background-color:#91cf61" |Non-randomized (RT)
 +
|-
 +
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Radioconjugate therapy====
+
====Chemotherapy====
−
*[[Tositumomab and I-131 (Bexxar)]]
+
*[[Mechlorethamine (Mustargen)]] 6 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 14
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 14
 +
'''28-day cycle for 6 to 8 cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''SWOG S0433:''' Friedberg JW, Unger JM, Burack WR, Gopal AK, Raju RN, Nademanee AP, Kaminski MS, Li H, Press OW, Miller TP, Fisher RI. R-CHOP with iodine-131 tositumomab consolidation for advanced stage diffuse large B-cell lymphoma (DLBCL): SWOG S0433. Br J Haematol. 2014 Aug;166(3):382-9. Epub 2014 Apr 18. [https://doi.org/10.1111/bjh.12906 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107050/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24749780 PubMed] NCT00107380
+
#Young RC, DeVita VT, Johnson RE. Hodgkin's disease in childhood. Blood. 1973 Aug;42(2):163-74. [http://www.bloodjournal.org/content/42/2/163.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/4793108 PubMed]
−
=Maintenance after first-line therapy=
+
#Kolygin BA. Combination chemotherapy of Hodgkin's disease in children. Cancer. 1976 Oct;38(4):1494-7. [https://doi.org/10.1002/1097-0142(197610)38:4%3C1494::AID-CNCR2820380408%3E3.0.CO;2-E link to original article] [https://pubmed.ncbi.nlm.nih.gov/991072 PubMed]
−
==Interferon alfa-2a monotherapy {{#subobject:d62b86|Regimen=1}}==
+
=Consolidation after upfront therapy=
 +
==C-MOPP {{#subobject:034931|Regimen=1}}==
 +
C-MOPP: '''<u>C</u>'''yclophospha'''<u>M</u>'''ide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
 +
<br>COPP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 3 MU TIW {{#subobject:0a71d7|Variant=1}}===
+
===Regimen variant #1, 2 cycles {{#subobject:cfcc4b|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"
−
!style="width: 25%"|Study
+
! style="width: 33%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 33%" |Years of enrollment
 +
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/112/13/4824.full Salles et al. 2008 (FL2000)]
+
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
+
|2002-2005
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''This variant was intended for patients older than 70 years.''
 
 
<div class="toccolours" style="background-color:#cbd5e8">
 
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
−
*[[Follicular_lymphoma#R-CHVP.2BI|R-CHVP+I]] versus [[#CHVP-I|CHVP+I]]
+
*[[#OPPA|OPPA]] x 2
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Immunotherapy====
+
====Chemotherapy====
−
*[[Interferon alfa-2a (Roferon-A)]] 3,000,000 units SC once per day on days 1, 3, 5 (three times per week)
+
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
−
'''7-day cycle for 78 cycles (18 months)'''
+
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 15
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15
 +
'''28-day cycle for 2 cycles'''
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, 4.5 MU TIW x 18 mo {{#subobject:0b61d7|Variant=1}}===
+
===Regimen variant #2, 4 cycles {{#subobject:228db9|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"
−
!style="width: 25%"|Study
+
! style="width: 33%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 33%" |Years of enrollment
 +
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/112/13/4824.full Salles et al. 2008 (FL2000)]
+
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
+
|2002-2005
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''This variant was intended for patients younger than 70 years.''
 
 
<div class="toccolours" style="background-color:#cbd5e8">
 
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
−
*[[Follicular_lymphoma#R-CHVP.2BI|R-CHVP+I]] versus [[#CHVP-I|CHVP+I]]
+
*[[#OPPA|OPPA]] x 2
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Immunotherapy====
+
====Chemotherapy====
−
*[[Interferon alfa-2a (Roferon-A)]] 4,500,000 units SC once per day on days 1, 3, 5 (three times per week)
+
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
−
'''7-day cycle for 78 cycles (18 months)'''
+
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
−
</div></div><br>
+
*[[Procarbazine (Matulane)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 15
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15
 +
'''28-day cycle for 4 cycles'''
 +
</div></div>
 +
===References===
 +
#'''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832
 +
==COPDAC {{#subobject:195ad7|Regimen=1}}==
 +
COPDAC: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>DAC</u>'''arbazine
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #3, 4.5 MU TIW, indefinitely {{#subobject:79c7d4|Variant=1}}===
+
===Regimen variant #1, 2 cycles {{#subobject:e9d06d|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"
−
!style="width: 25%"|Study
+
! style="width: 33%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 33%" |Years of enrollment
 +
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2006.06.4618 Herold et al. 2007 (OSHO-39)]
+
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
−
|style="background-color:#91cf61"|Non-randomized portion of RCT
+
|2002-2005
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#cbd5e8">
 
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
−
*[[#MCP_.28Prednisolone.29|MCP]] versus [[Follicular_lymphoma#R-MCP|R-MCP]]
+
*[[#OEPA|OEPA]] x 2
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Immunotherapy====
+
====Chemotherapy====
−
*[[Interferon alfa-2a (Roferon-A)]] 4,500,000 units (route not specified) once per day on days 1, 3, 5 (three times per week)
+
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
−
'''7-day cycles'''
+
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Dacarbazine (DTIC)]] 250 mg/m<sup>2</sup> IV once per day on days 1 to 4
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15
 +
'''28-day cycle for 2 cycles'''
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #4, 5 MU TIW {{#subobject:79c0a4|Variant=1}}===
+
===Regimen variant #2, 4 cycles {{#subobject:515d30|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"
−
!style="width: 20%"|Study
+
! style="width: 33%" |Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 33%" |Years of enrollment
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/104/9/2667.long Lenz et al. 2004]
+
|[https://doi.org/10.1200/jco.2009.26.9381 Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
−
|1996-2000
+
|2002-2005
−
| style="background-color:#1a9851" |Phase 3 (C)
+
| style="background-color:#91cf61" |Phase 2
−
|[[#Cyclophosphamide_.26_TBI.2C_then_auto_HSCT_88|Cy/TBI, then auto HSCT]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#cbd5e8">
 
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
−
*[[#CHOP|CHOP]] or [[#MCP|MCP]]
+
*[[#OEPA|OEPA]] x 2
 
</div>
 
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Dacarbazine (DTIC)]] 250 mg/m<sup>2</sup> IV once per day on days 1 to 4
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 15
 +
'''28-day cycle for 4 cycles'''
 +
</div></div>
 +
===References ===
 +
#'''GPOH-HD-2002:''' Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. [https://doi.org/10.1200/jco.2009.26.9381 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20625128 PubMed] NCT00416832
 +
=Maintenance after upfront therapy=
 +
==Bacillus Calmette-Guérin (BCG) monotherapy {{#subobject:e1fd72|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:52ca75|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/10.1056/NEJM197412052912305 Sokal et al. 1974]
 +
|1965-1967
 +
| style="background-color:#91cf61" |Randomized, <20 pts in this subgroup (E-esc)
 +
|[[Hodgkin_lymphoma_-_null_regimens#Observation_2|Observation]]
 +
| style="background-color:#1a9850" |Superior PFS
 +
|-
 +
|}
 +
''Note: this study was open to patients with "malignant lymphoma" but the majority had Hodgkin disease.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
−
*[[Interferon alfa-2a (Roferon-A)]] 5,000,000 units SC once per day on days 1, 3, 5 (three times per week)
+
*[[Bacillus Calmette-Guérin (BCG)]]
−
'''7-day cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Lenz G, Dreyling M, Schiegnitz E, Forstpointner R, Wandt H, Freund M, Hess G, Truemper L, Diehl V, Kropff M, Kneba M, Schmitz N, Metzner B, Pfirrmann M, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 1;104(9):2667-74. Epub 2004 Jul 6. [http://www.bloodjournal.org/content/104/9/2667.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15238420 PubMed]
+
#Sokal JE, Aungst CW, Snyderman M. Delay in progression of malignant lymphoma after BCG vaccination. N Engl J Med. 1974 Dec 5;291(23):1226-30. [https://doi.org/10.1056/NEJM197412052912305 link to original article] [https://pubmed.ncbi.nlm.nih.gov/4609380 PubMed]
−
# '''OSHO-39:''' Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, Dölken G, Naumann R, Knauf W, Freund M, Rohrberg R, Höffken K, Franke A, Ittel T, Kettner E, Haak U, Mey U, Klinkenstein C, Assmann M, von Grünhagen U; East German Study Group Hematology and Oncology Study. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007 May 20;25(15):1986-92. Epub 2007 Apr 9. [https://doi.org/10.1200/jco.2006.06.4618 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17420513 PubMed] NCT00269113
+
=Relapsed or refractory, salvage therapy =
−
# '''FL2000:''' Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF, Haioun C, Brice P, Mahé B, Bouabdallah R, Audhuy B, Ferme C, Dartigeas C, Feugier P, Sebban C, Xerri L, Foussard C. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008 Dec 15;112(13):4824-31. Epub 2008 Sep 17. [http://www.bloodjournal.org/content/112/13/4824.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18799723 PubMed] NCT00136552
+
==ABDIC {{#subobject:c5c5ab|Regimen=1}}==
−
## '''Update:''' Bachy E, Houot R, Morschhauser F, Sonet A, Brice P, Belhadj K, Cartron G, Audhuy B, Fermé C, Feugier P, Sebban C, Delwail V, Maisonneuve H, Le Gouill S, Lefort S, Brousse N, Foussard C, Salles G; Groupe d'Etude des Lymphomes de l'Adulte (GELA). Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma. Haematologica. 2013 Jul;98(7):1107-14. Epub 2013 May 3. [http://www.haematologica.org/content/98/7/1107.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696615/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23645690 PubMed]
+
ABDIC: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>DI</u>'''C (Dacarbazine), '''<u>C</u>'''CNU (Lomustine), Prednisone
−
=Relapsed or refractory=
 
−
==CHOP {{#subobject:3a1597|Regimen=1}}==
 
−
CHOP: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:9d2627|Variant=1}}===
+
===Regimen {{#subobject:4ba1e1|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"
−
!style="width: 20%"|Study
+
! style="width: 25%" |Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!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/108/10/3295.long Van Oers et al. 2006 (EORTC 20981)]
+
|[https://doi.org/10.1002/1097-0142(19801201)46:11%3C2349::AID-CNCR2820461105%3E3.0.CO;2-V Rodgers et al. 1980]
−
|1998-2004
+
| style="background-color:#91cf61" |Phase 2
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Follicular_lymphoma#R-CHOP_2|R-CHOP]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
+
*[[Doxorubicin (Adriamycin)]]
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
*[[Bleomycin (Blenoxane)]]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Dacarbazine (DTIC)]]
 +
*[[Lomustine (CCNU)]]
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
+
*[[Prednisone (Sterapred)]]
−
'''21-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders (PR or CR): [[Follicular_lymphoma#Rituximab_monotherapy.2C_extended_course_2|Rituximab]] maintenance versus [[Follicular_lymphoma#Observation_3|no further treatment]]
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''EORTC 20981:''' van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van 't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. Epub 2006 Jul 27. [http://www.bloodjournal.org/content/108/10/3295.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16873669 PubMed] NCT00004179
+
#Rodgers RW, Gamble JF, Loh KK, Shullenberger CC. Adriamycin, bleomycin, DIC, CCNU, and prednisone (ABDIC) chemotherapy in MOPP-resistant Hodgkin's disease. Cancer. 1980 Dec 1;46(11):2349-55. [https://doi.org/10.1002/1097-0142(19801201)46:11%3C2349::AID-CNCR2820461105%3E3.0.CO;2-V link to original article] [https://pubmed.ncbi.nlm.nih.gov/6159961 PubMed]
−
##'''Update:''' van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. Epub 2010 May 3. [https://doi.org/10.1200/jco.2009.26.5827 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20439641 PubMed]
+
##'''Update:''' Tannir N, Hagemeister F, Velasquez W, Cabanillas F. Long-term follow-up with ABDIC salvage chemotherapy of MOPP-resistant Hodgkin's disease. J Clin Oncol. 1983 Jul;1(7):432-9. [https://doi.org/10.1200/jco.1983.1.7.432 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6199478 PubMed]
−
==FCM {{#subobject:294f6d|Regimen=1}}==
+
==ABVD {{#subobject:c5a35d|Regimen=1}}==
−
FCM: '''<u>F</u>'''ludarabine, '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''itoxantrone
+
ABVD: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''acarbazine
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:f3f288|Variant=1}}===
+
===Regimen {{#subobject:ae32ee|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"
−
!style="width: 20%"|Study
+
! style="width: 25%" | Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
|-
−
!style="width: 20%"|Comparator
+
|[https://doi.org/10.1002/1097-0142(197806)41:6%3C2107::AID-CNCR2820410606%3E3.0.CO;2-L Krikorian et al. 1978]
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
| style="background-color:#91cf61" |Phase 2
 +
|-
 +
|[https://doi.org/10.1007/bf00254081 Santoro & Bonadonna 1979]
 +
| style="background-color:#91cf61" | Non-randomized
 +
|-
 +
|[https://doi.org/10.7326/0003-4819-96-2-139 Santoro et al. 1982a]
 +
| style="background-color:#91cf61" |Non-randomized
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/104/10/3064.long Forstpointner et al. 2004]
+
|[https://doi.org/10.7326/0003-4819-101-4-440 Harker et al. 1984]
−
|1998-2001
+
| style="background-color:#91cf61" |Non-randomized
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Follicular_lymphoma#R-FCM_2|R-FCM]]
 
−
|style="background-color:#fc8d59"|Seems to have inferior PFS
 
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#b3e2cd">
+
''This is for historical interest only; ABVD is no longer used in the salvage setting.''
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 3
+
*[[Doxorubicin (Adriamycin)]]
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 4 hours on days 1 to 3
+
*[[Bleomycin (Blenoxane)]]
−
*[[Mitoxantrone (Novantrone)]] 8 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+
*[[Vinblastine (Velban)]]
−
'''28-day cycle for 4 cycles'''
+
*[[Dacarbazine (DTIC)]]
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders (PR or CR): [[Follicular_lymphoma#Rituximab_monotherapy.2C_abbreviated_course_2|Rituximab]] maintenance versus [[Follicular_lymphoma#Observation_3|no further treatment]]
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. [http://www.bloodjournal.org/content/104/10/3064.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15284112 PubMed]
+
#Krikorian JG, Portlock CS, Rosenberg SA. Treatment of advanced Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) after failure of MOPP therapy. Cancer. 1978 Jun;41(6):2107-11. [https://doi.org/10.1002/1097-0142(197806)41:6%3C2107::AID-CNCR2820410606%3E3.0.CO;2-L link to original article] [https://pubmed.ncbi.nlm.nih.gov/77716 PubMed]
−
## '''Update:''' Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W; German Low Grade Lymphoma Study Group (GLSG). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003-8. Epub 2006 Aug 31. [http://www.bloodjournal.org/content/108/13/4003.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16946304 PubMed]
+
#Santoro A, Bonadonna G. Prolonged disease-free survival in MOPP-resistant Hodgkin's disease after treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). Cancer Chemother Pharmacol. 1979;2(2):101-5. [https://doi.org/10.1007/bf00254081 link to original article] [https://pubmed.ncbi.nlm.nih.gov/93984 PubMed]
−
==Fludarabine monotherapy {{#subobject:f8gyaa|Regimen=1}}==
+
#Santoro A, Bonfante V, Bonadonna G. Salvage chemotherapy with ABVD in MOPP-resistant Hodgkin's disease. Ann Intern Med. 1982 Feb;96(2):139-43. [https://doi.org/10.7326/0003-4819-96-2-139 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6174060 PubMed]
 +
#Harker WG, Kushlan P, Rosenberg SA. Combination chemotherapy for advanced Hodgkin's disease after failure of MOPP: ABVD and B-CAVe. Ann Intern Med. 1984 Oct;101(4):440-6. [https://doi.org/10.7326/0003-4819-101-4-440 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6206757 PubMed]
 +
==B-CAVe {{#subobject:41a31c|Regimen=1}}==
 +
B-CAVe: '''<u>B</u>'''leomycin, '''<u>C</u>'''CNU (Lomustine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>V</u>'''inblastin'''<u>e</u>'''
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:5798ue|Variant=1}}===
+
===Regimen {{#subobject:c53f0c|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"
−
!style="width: 20%"|Study
+
! style="width: 25%" |Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
|-
−
!style="width: 20%"|Comparator
+
|[https://doi.org/10.1002/1097-0142(197805)41:5%3C1670::AID-CNCR2820410504%3E3.0.CO;2-Y Porzig et al. 1978]
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
| style="background-color:#91cf61" |Non-randomized
 
|-
 
|-
−
|[https://doi.org/10.1200/JCO.2002.11.068 Klasa et al. 2002]
+
|[https://doi.org/10.7326/0003-4819-101-4-440 Harker et al. 1984]
−
|1993-1996
+
| style="background-color:#91cf61" |Non-randomized
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#CVP_88|CVP]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 5
+
*[[Bleomycin (Blenoxane)]]
−
'''28-day cycles'''
+
*[[Lomustine (CCNU)]]
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Vinblastine (Velban)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Klasa RJ, Meyer RM, Shustik C, Sawka CA, Smith A, Guévin R, Maksymiuk A, Rubinger M, Samosh M, Laplante S, Grenier JF. Randomized phase III study of fludarabine phosphate versus cyclophosphamide, vincristine, and prednisone in patients with recurrent low-grade non-Hodgkin's lymphoma previously treated with an alkylating agent or alkylator-containing regimen. J Clin Oncol. 2002 Dec 15;20(24):4649-54. [https://doi.org/10.1200/JCO.2002.11.068 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488409 PubMed]
+
#Porzig KJ, Portlock CS, Robertson A, Rosenberg SA. Treatment of advanced Hodgkin's disease with B-CAVE following MOPP failure. Cancer. 1978 May;41(5):1670-5. [https://doi.org/10.1002/1097-0142(197805)41:5%3C1670::AID-CNCR2820410504%3E3.0.CO;2-Y link to original article] [https://pubmed.ncbi.nlm.nih.gov/77180 PubMed]
−
==FMP {{#subobject:f1669a|Regimen=1}}==
+
#Harker WG, Kushlan P, Rosenberg SA. Combination chemotherapy for advanced Hodgkin's disease after failure of MOPP: ABVD and B-CAVe. Ann Intern Med. 1984 Oct;101(4):440-6. [https://doi.org/10.7326/0003-4819-101-4-440 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6206757 PubMed]
−
FMP: '''<u>F</u>'''ludarabine, '''<u>M</u>'''itoxantrone, '''<u>P</u>'''rednisone
+
==BVCPP {{#subobject:cb42cf|Regimen=1}}==
 +
BVCPP: '''<u>B</u>'''CNU (Carmustine), '''<u>V</u>'''inblastine, '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:57301e|Variant=1}}===
+
===Regimen {{#subobject:514e7d|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 33%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1111/j.1600-0609.1995.tb00269.x Zinzani et al. 1995a]
+
|[https://doi.org/10.1002/1097-0142%28197811%2942%3A5%3C2101%3A%3AAID-CNCR2820420504%3E3.0.CO%3B2-M Durant et al. 1978]
−
|style="background-color:#91cf61"|Phase 2
+
|1971-1975
 +
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]]
+
*[[Carmustine (BCNU)]]
−
*[[Mitoxantrone (Novantrone)]]
+
*[[Vinblastine (Velban)]]
 +
*[[Cyclophosphamide (Cytoxan)]]
 +
*[[Procarbazine (Matulane)]]
 
====Glucocorticoid therapy====
 
====Glucocorticoid therapy====
 
*[[Prednisone (Sterapred)]]
 
*[[Prednisone (Sterapred)]]
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*Patients who achieved CR: No additional therapy versus [[Hodgkin_lymphoma#MOPP|MOPP]] x 6 versus BVCPP x 6 additional cycles
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Zinzani PL, Bendandi M, Tura S. FMP regimen (fludarabine, mitoxantrone, prednisone) as therapy in recurrent low-grade non-Hodgkin's lymphoma. Eur J Haematol. 1995 Oct;55(4):262-6. [https://doi.org/10.1111/j.1600-0609.1995.tb00269.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/7589345 PubMed]
+
#Durant JR, Gams RA, Velez-Garcia E, Bartolucci A, Wirtschafter D, Dorfman R. BCNU, velban, cyclophosphamide, procarbazine, and prednisone (BVCPP) in advanced Hodgkin's disease. Cancer. 1978 Nov;42(5):2101-10. [https://doi.org/10.1002/1097-0142%28197811%2942%3A5%3C2101%3A%3AAID-CNCR2820420504%3E3.0.CO%3B2-M link to original article] [https://pubmed.ncbi.nlm.nih.gov/719600 PubMed]
−
==Fludarabine & Rituximab (FR) {{#subobject:c96961|Regimen=1}}==
+
==BVDS {{#subobject:3a24f9|Regimen=1}}==
−
FR: '''<u>F</u>'''ludarabine & '''<u>R</u>'''ituximab
+
BVDS: '''<u>B</u>'''leomycin, '''<u>V</u>'''inblastine, '''<u>D</u>'''oxorubicin, '''<u>S</u>'''treptozocin
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:5ba252|Variant=1}}===
+
===Regimen {{#subobject:41d09e|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
+
{| class="wikitable" style="width: 40%; text-align:center;"
−
!style="width: 20%"|Study
+
! style="width: 25%" |Study
−
!style="width: 20%"|Years of enrollment
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
|-
−
!style="width: 20%"|Comparator
+
|[https://jamanetwork.com/journals/jama/article-abstract/350618 Vinciguerra et al. 1977]
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
| style="background-color:#ffffbe" |Non-randomized, <20 pts
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Bleomycin (Blenoxane)]]
 +
*[[Vinblastine (Velban)]]
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Streptozocin (Zanosar)]]
 +
</div></div>
 +
===References===
 +
#Vinciguerra V, Coleman M, Jarowski CI, Degnan TJ, Silver RT. A new combination chemotherapy for resistant Hodgkin disease. JAMA. 1977 Jan 3;237(1):33-5. [https://jamanetwork.com/journals/jama/article-abstract/350618 link to original article] [https://pubmed.ncbi.nlm.nih.gov/62854 PubMed]
 +
==CEP {{#subobject:a1a2cc|Regimen=1}}==
 +
CEP: '''<u>C</u>'''CNU (Lomustine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednimustine
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:a353e9|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/10.1016/S1470-2045(15)00447-7 Rummel et al. 2015 (StiL NHL 2-2003)]
+
|[https://pubmed.ncbi.nlm.nih.gov/2420012 Santoro et al. 1986]
−
|2003-2010
+
| style="background-color:#91cf61" |Non-randomized
−
|style="background-color:#1a9851"|Phase 3 (C)
 
−
|[[Follicular_lymphoma#Bendamustine_.26_Rituximab_.28BR.29_2|BR]]
 
−
|style="background-color:#d73027"|Inferior PFS
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 25 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 3
+
*[[Lomustine (CCNU)]]
−
====Targeted therapy====
+
*[[Etoposide (Vepesid)]]
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+
*[[Prednimustine (Stereocyt)]]
−
'''28-day cycle for up to 6 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- # '''Abstract:''' Mathias J. Rummel, MD, PhD, Ulrich Kaiser, MD, Christina Balser, Martina Beate Stauch, Wolfram Brugger, MD, PhD, Manfred Welslau, Norbert Niederle, Christoph Losem, Harald Ballo, Eckhart Weidmann, Ulrich von Gruenhagen, Lothar Mueller, Michael Sandherr, MD, Julia Vereschagina, Axel Hinke and Juergen Barth. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab In Patients with Relapsed Follicular, Indolent and Mantle Cell Lymphomas – Final Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting 2010, Abstract 856 [https://ash.confex.com/ash/2010/webprogram/Paper26917.html link to abstract]
+
#Santoro A, Viviani S, Valagussa P, Bonfante V, Bonadonna G. CCNU, etoposide, and prednimustine (CEP) in refractory Hodgkin's disease. Semin Oncol. 1986 Mar;13(1 Suppl 1):23-6. [https://pubmed.ncbi.nlm.nih.gov/2420012 PubMed]
−
## '''Update:''' '''Abstract:''' Mathias J. Rummel, MD, Christina Balser, MD, Ulrich Kaiser, MD, Hans Peter Böck, Martina Beate Stauch, MD, Andrea Heider, PhD, Manfred Welslau, Christoph Losem, Eckhart Weidmann, Wolfgang Blau, MD, Alexander Burchardt, MD, Jürgen Barth, Frank Kauff, PhD, Axel Hinke, PhD and Wolfram Brugger, MD. Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab in Patients with Relapsed Follicular, Indolent, or Mantle Cell Lymphomas – 8-Year Follow-up Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany). ASH Annual Meeting 2014, Abstract 145 [https://ash.confex.com/ash/2014/webprogram/Paper69154.html link to abstract] -->
+
==CVB {{#subobject:b2b2cc|Regimen=1}}==
−
# '''StiL NHL 2-2003:''' Rummel M, Kaiser U, Balser C, Stauch M, Brugger W, Welslau M, Niederle N, Losem C, Boeck HP, Weidmann E, von Gruenhagen U, Mueller L, Sandherr M, Hahn L, Vereshchagina J, Kauff F, Blau W, Hinke A, Barth J; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial. Lancet Oncol. 2016 Jan;17(1):57-66. Epub 2015 Dec 5. [https://doi.org/10.1016/S1470-2045(15)00447-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26655425 PubMed] NCT01456351
+
CVB: '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''inblastine, '''<u>B</u>'''leomycin
−
==Idelalisib monotherapy {{#subobject:7fef70|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:cea36|Variant=1}}===
+
===Regimen {{#subobject:a464e9|Variant=1}}===
−
{| class="wikitable" style="width: 60%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"
−
!style="width: 33%"|Study
+
! style="width: 25%" |Study
−
!style="width: 33%"|Years of enrollment
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ Gopal et al. 2014 (DELTA)]
+
|[https://doi.org/10.1016/S0140-6736(75)92069-3 Goldman & Dawson 1975]
−
|2011-2012
+
| style="background-color:#91cf61" |Non-randomized
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
+
====Chemotherapy====
−
*[[Idelalisib (Zydelig)]] 150 mg PO twice per day
+
*[[Lomustine (CCNU)]]
−
'''Continued indefinitely'''
+
*[[Vinblastine (Velban)]]
 +
*[[Bleomycin (Blenoxane)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
#'''DELTA:''' Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Mar 13;370(11):1008-18. Epub 2014 Jan 22. [https://doi.org/10.1056/NEJMoa1314583 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24450858 PubMed] NCT01282424
+
#Goldman JM, Dawson AA. Combination therapy for advanced resistant Hodgkin's disease. Lancet. 1975 Dec 20;2(7947):1224-7. [https://doi.org/10.1016/S0140-6736(75)92069-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/53720 PubMed]
−
##'''Update:''' '''Abstract:''' Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). Blood 2014 124:1708. [http://www.bloodjournal.org/content/124/21/1708 link to abstract]
+
==CVPP {{#subobject:be8f99|Regimen=1}}==
−
==Interferon alfa monotherapy {{#subobject:10dcf2|Regimen=1}}==
+
CVPP: '''<u>C</u>'''CNU (Lomustine), '''<u>V</u>'''inblastine, '''<u>P</u>'''rocarbazine, '''<u>P</u>'''rednisone
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:042fbd|Variant=1}}===
+
===Regimen {{#subobject:f32d98|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
!style="width: 25%"|Study
+
! style="width: 20%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! 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/NEJM198411013111803 Foon et al. 1984]
+
|[https://doi.org/10.1200/JCO.1986.4.6.838 Vinciguerra et al. 1986]
−
|style="background-color:#91cf61"|Phase 2
+
|1975-1981
 +
| style="background-color:#1a9851" |Randomized (C)
 +
|1. [[#ABOS_99|ABOS]]<br>2. [[#CVPP.2FABOS_99|CVPP/ABOS]]
 +
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Immunotherapy====
+
====Chemotherapy====
−
*[[:Category:Interferons|Interferon alfa]]
+
*[[Lomustine (CCNU)]]
 +
*[[Vinblastine (Velban)]]
 +
*[[Procarbazine (Matulane)]]
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Foon KA, Sherwin SA, Abrams PG, Longo DL, Fer MF, Stevenson HC, Ochs JJ, Bottino GC, Schoenberger CS, Zeffren J, Jaffe ES, Oldham RK. Treatment of advanced non-Hodgkin's lymphoma with recombinant leukocyte A interferon. N Engl J Med. 1984 Nov 1;311(18):1148-52. [https://doi.org/10.1056/NEJM198411013111803 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6482933 PubMed]
+
#Vinciguerra V, Propert KJ, Coleman M, Anderson JR, Stutzman L, Pajak TF, Nissen NI, Frizzera G, Gottlieb A, Holland JF; [[Study_Groups#CALGB|CALGB]]. Alternating cycles of combination chemotherapy for patients with recurrent Hodgkin's disease following radiotherapy: a prospectively randomized study by the Cancer and Leukemia Group B. J Clin Oncol. 1986 Jun;4(6):838-46. [https://doi.org/10.1200/JCO.1986.4.6.838 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2423652 PubMed]
−
==<sup>131</sup>Iodine-Tositumomab monotherapy {{#subobject:e69735|Regimen=1}}==
+
==SCAB {{#subobject:04355f|Regimen=1}}==
 +
SCAB: '''<u>S</u>'''treptozocin, '''<u>C</u>'''CNU (Lomustine), '''<u>A</u>'''driamycin (Doxorubicin), '''<u>B</u>'''leomycin
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:3515b6|Variant=1}}===
+
===Regimen {{#subobject:5c34db|Variant=1}}===
−
{| class="wikitable" style="width: 60%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"
−
!style="width: 33%"|Study
+
! style="width: 25%" |Study
−
!style="width: 33%"|Years of enrollment
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
 
|-
 
|-
−
|[https://doi.org/10.1056/NEJM199308123290703 Kaminski et al. 1993]
+
|[https://doi.org/10.1002/mpo.2950030106 Levi et al. 1977]
−
|NR
 
 
| style="background-color:#ffffbe" |Non-randomized, <20 pts
 
| style="background-color:#ffffbe" |Non-randomized, <20 pts
 
|-
 
|-
−
|[https://doi.org/10.1016/s0140-6736(95)92225-3 Press et al. 1995]
+
|}
−
|NR
+
<div class="toccolours" style="background-color:#b3e2cd">
−
|style="background-color:#91cf61"|Phase 2
+
====Chemotherapy====
 +
*[[Streptozocin (Zanosar)]]
 +
*[[Lomustine (CCNU)]]
 +
*[[Doxorubicin (Adriamycin)]]
 +
*[[Bleomycin (Blenoxane)]]
 +
</div></div>
 +
===References===
 +
#Levi JA, Wiernik PH, Diggs CH. Combination chemotherapy of advanced previously treated Hodgkin's disease with streptozotocin, CCNU, adriamycin and bleomycin. Med Pediatr Oncol. 1977;3(1):33-40. [https://doi.org/10.1002/mpo.2950030106 link to original article] [https://pubmed.ncbi.nlm.nih.gov/65727 PubMed]
 +
=Relapsed or refractory, further lines of therapy=
 +
==Carmustine monotherapy {{#subobject:f072cf|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:d61e28|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.2001.19.19.3918 Kaminski et al. 2001 (RIT-II-004)]
+
|[https://doi.org/10.1056/NEJM197108262850902 Young et al. 1971]
−
|1996-1998
+
| style="background-color:#91cf61" |Non-randomized
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
 
|-
 
|-
−
|[https://doi.org/10.1200/JCO.2005.07.040 Horning et al. 2004 (CP-97-012)]
+
|}
−
|1998-1999
+
<div class="toccolours" style="background-color:#b3e2cd">
−
|style="background-color:#91cf61"|Phase 2 (RT)
+
====Chemotherapy====
 +
*[[Carmustine (BCNU)]]
 +
</div></div>
 +
===References===
 +
#Young RC, DeVita VT Jr, Serpick AA, Canellos GP. Treatment of advanced Hodgkin's disease with (1,3 bis (2-chloroethyl)-1-nitrosourea) BCNU. N Engl J Med. 1971 Aug 26;285(9):475-9. [https://doi.org/10.1056/NEJM197108262850902 link to original article] [https://pubmed.ncbi.nlm.nih.gov/5558887 PubMed]
 +
==Doxorubicin & Lomustine {{#subobject:7e7049|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:e9f038|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/10.3109/10428194.2014.894190 Olney et al. 2014 (SB-393229/032)]
+
|[https://jamanetwork.com/journals/jama/article-abstract/355977 Williams & Einhorn 1977]
−
|2004-2007
+
| style="background-color:#ffffbe" |Non-randomized, <20 pts
−
|style="background-color:#91cf61"|Phase 2
 
 
|-
 
|-
 
|}
 
|}
−
''Note: Kiminski et al. 1993 and Press et al. 1995 are included here for historic context but had different treatment details.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Radioconjugate therapy, dosimetric step====
+
====Chemotherapy====
−
*On Day 0, infusions of:
+
*[[Doxorubicin (Adriamycin)]]
−
**Tositumomab 450 mg IV over 1 hour
+
*[[Lomustine (CCNU)]]
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
 
−
**First scan of whole body dosimetry & redistribution
 
−
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 
−
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 
−
====Radioconjugate therapy, therapeutic step====
 
−
*Any day from day 7 to 15, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 
−
***65 cGy total body dose used for patients with platelet counts of 100 to 150,000/mm3
 
−
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg PO as premedication for [[Tositumomab and I-131 (Bexxar)]]
 
−
*Potassium iodide  (SSKI, saturated solution of potassium iodide) 2 drops PO three times per day starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion; may also use Lugol’s solution or potassium iodide tablets
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Kaminski MS, Zasadny KR, Francis IR, Milik AW, Ross CW, Moon SD, Crawford SM, Burgess JM, Petry NA, Butchko GM, Glenn SD, Wahl RL. Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N Engl J Med. 1993 Aug 12;329(7):459-65. [https://doi.org/10.1056/NEJM199308123290703 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7687326 PubMed]
+
#Williams SD, Einhorn LH. Combination chemotherapy with doxorubicin and lomustine: treatment of refractory Hodgkin's disease. JAMA. 1977 Oct 10;238(15):1659-61. [https://jamanetwork.com/journals/jama/article-abstract/355977 link to original article] [https://pubmed.ncbi.nlm.nih.gov/578254 PubMed]
−
# Press OW, Eary JF, Appelbaum FR, Martin PJ, Nelp WB, Glenn S, Fisher DR, Porter B, Matthews DC, Gooley T, Bernstein ID. Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Lancet. 1995 Aug 5;346(8971):336-40. [https://doi.org/10.1016/s0140-6736(95)92225-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7623531 PubMed]
+
==Panobinostat monotherapy {{#subobject:ba10d6|Regimen=1}}==
−
# '''RIT-II-004:''' Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L, Lister TA, Stagg RJ, Tidmarsh GF, Kroll S, Wahl RL, Knox SJ, Vose JM. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2001 Oct 1;19(19):3918-28. [https://doi.org/10.1200/jco.2001.19.19.3918 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11579112 PubMed]
 
−
# '''CP-97-012:''' Horning SJ, Younes A, Jain V, Kroll S, Lucas J, Podoloff D, Goris M. Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol. 2005 Feb 1;23(4):712-9. Epub 2004 Dec 21. [https://doi.org/10.1200/JCO.2005.07.040 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15613695 PubMed]
 
−
# '''Meta-analysis:''' Fisher RI, Kaminski MS, Wahl RL, Knox SJ, Zelenetz AD, Vose JM, Leonard JP, Kroll S, Goldsmith SJ, Coleman M. Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin's lymphomas. J Clin Oncol. 2005 Oct 20;23(30):7565-73. Epub 2005 Sep 26. [https://doi.org/10.1200/jco.2004.00.9217 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16186600 PubMed]
 
−
# '''SB-393229/032:''' Olney HJ, Freeman MA, Stewart DA, Mangel JE, White DJ, Elia-Pacitti JO. Prolonged progression-free survival and preserved quality of life in the Canadian prospective study of tositumomab and iodine(131)-tositumomab for previously treated, rituximab-exposed, indolent non-Hodgkin lymphoma. Leuk Lymphoma. 2014 Dec;55(12):2754-60. Epub 2014 Apr 3. [https://doi.org/10.3109/10428194.2014.894190 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24528219 PubMed] NCT00240565
 
−
==Ofatumumab monotherapy {{#subobject:a875bf|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:ddfe7d|Variant=1}}===  
+
===Regimen {{#subobject:0c34a8|Variant=1}}===
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
−
!style="width: 20%"|Study
+
!style="width: 25%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 25%"|Years of enrollment
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|Comparator
+
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/111/12/5486.long Hagenbeek et al. 2008 (Hx-CD20-001)]
+
|[https://doi.org/10.1200/jco.2011.38.1350 Younes et al. 2012 (CLBH589E2214)]
−
|2004-2005
+
|2008-2009
−
| style="background-color:#91cf61" |Phase 1/2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.bloodjournal.org/content/119/16/3698.long Czucman et al. 2012 (405 Study)]
 
−
|2006-2008
 
 
| style="background-color:#91cf61" |Phase 2
 
| style="background-color:#91cf61" |Phase 2
−
| style="background-color:#d3d3d3" |
+
|Investigator assessment: 27% <br>Central review: 22%
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7448588/ Maloney et al. 2020 (HOMER)]
 
−
|2010-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[Follicular_lymphoma#Rituximab_monotherapy_3|Rituximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
 
|-
 
|-
 
|}
 
|}
−
''Note: there was no MTD determined in Hx-CD20-001.''
+
''Patients had progressed after auto HSCT and had a median of 4 prior systemic regimens (range 2 to 7).''
−
<div class="toccolours" style="background-color:#b3e2cd">
 
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Ofatumumab (Arzerra)]] as follows:
+
*[[Panobinostat (Farydak)]] 40 mg PO three times per week (e.g., MWF)
−
**Cycle 1: 300 mg IV once on day 1, then 1000 mg IV once per day on days 8, 15, 22
+
'''21-day cycles'''
−
**Cycle 2: 1000 mg IV once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 1000 mg (no route specified) before each dose of [[Ofatumumab (Arzerra)]]
 
−
*[[Cetirizine (Zyrtec)]] 10 mg (or equivalent) PO before each dose of [[Ofatumumab (Arzerra)]]
 
−
*[[Prednisolone (Millipred)]] (or equivalent) 100 mg before dose 1 and 2 of [[Ofatumumab (Arzerra)]]
 
−
'''28-day cycle for 2 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
#'''Hx-CD20-001:''' Hagenbeek A, Gadeberg O, Johnson P, Pedersen LM, Walewski J, Hellmann A, Link BK, Robak T, Wojtukiewicz M, Pfreundschuh M, Kneba M, Engert A, Sonneveld P, Flensburg M, Petersen J, Losic N, Radford J. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood. 2008 Jun 15;111(12):5486-95. Epub 2008 Apr 4. [http://www.bloodjournal.org/content/111/12/5486.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/18390837 PubMed] NCT00092274
+
# '''CLBH589E2214:''' Younes A, Sureda A, Ben-Yehuda D, Zinzani PL, Ong TC, Prince HM, Harrison SJ, Kirschbaum M, Johnston P, Gallagher J, Le Corre C, Shen A, Engert A. Panobinostat in patients with relapsed/refractory Hodgkin's lymphoma after autologous stem-cell transplantation: results of a phase II study. J Clin Oncol. 2012 Jun 20;30(18):2197-203. Epub 2012 Apr 30. [https://doi.org/10.1200/jco.2011.38.1350 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22547596 PubMed] NCT00742027
−
#'''405 Study:''' Czuczman MS, Fayad L, Delwail V, Cartron G, Jacobsen E, Kuliczkowski K, Link BK, Pinter-Brown L, Radford J, Hellmann A, Gallop-Evans E, DiRienzo CG, Goldstein N, Gupta I, Jewell RC, Lin TS, Lisby S, Schultz M, Russell CA, Hagenbeek A; 405 Study Investigators. Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood. 2012 Apr 19;119(16):3698-704. Epub 2012 Mar 2. [http://www.bloodjournal.org/content/119/16/3698.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22389254 PubMed] NCT00394836
+
==Sirolimus & Vorinostat {{#subobject:273a59|Regimen=1}}==
−
#'''HOMER:''' Maloney DG, Ogura M, Fukuhara N, Davis J, Lasher J, Izquierdo M, Banerjee H, Tobinai K. A phase 3 randomized study (HOMER) of ofatumumab vs rituximab in iNHL relapsed after rituximab-containing therapy. Blood Adv. 2020 Aug 25;4(16):3886-3893. [https://doi.org/10.1182/bloodadvances.2020001942 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7448588/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32810220 PubMed] NCT01200589
 
−
==Umbralisib monotherapy {{#subobject:98gja1|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:1y82ef|Variant=1}}===
+
===Regimen {{#subobject:91d698|Variant=1}}===
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
Line 1,152: Line 1,326:
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8148421/ Fowler et al. 2021 (UNITY-NHL)]
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|[https://doi.org/10.1158/1078-0432.ccr-20-1215 Janku et al. 2020 (MDACC 2009-0729)]
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|2017-2018
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|2010-2015
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| style="background-color:#91cf61" |Phase 2b (RT)
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| style="background-color:#91cf61" |Non-randomized
 
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|}
 
|}
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<div class="toccolours" style="background-color:#b3e2cd">
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''This is a very heavily pre-treated cohort, median of 6 prior therapies; doses here are one level below MTD and are proposed as the ongoing doses to be studied.''
 +
====Immunosuppressive therapy====
 +
*[[Sirolimus (Rapamune)]] 4 mg PO once per day
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Umbralisib (Ukoniq)]] 800 mg PO once per day
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*[[Vorinostat (Zolinza)]] as follows:
−
'''Continued indefinitely'''
+
**Cycle 1: 300 mg PO once per day on days 7 to 28
 +
**Subsequent cycles: 300 mg PO once per day on days 1 to 28
 +
'''28-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- #'''Abstract:''' Nathan Hale Fowler, Felipe Samaniego, Wojciech Jurczak, Ewa Lech-Maranda, Nilanjan Ghosh, Piers Patten, James Andrew Reeves, Lori Ann Leslie, Julio C. Chavez, Paolo Ghia, Corrado Tarella, John M. Burke, Jeff Porter Sharman, Kathryn Kolibaba, Owen A. O'Connor, Chan Cheah, Hari P. Miskin, Peter Sportelli, Michael S. Weiss, and Pier Luigi Zinzani. Umbralisib monotherapy demonstrates efficacy and safety in patients with relapsed/refractory marginal zone lymphoma: A multicenter, open label, registration directed phase II study. Journal of Clinical Oncology 2019 37:15_suppl, 7506-7506 [https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.7506 link to abstract] -->
+
#'''MDACC 2009-0729:''' Janku F, Park H, Call SG, Madwani K, Oki Y, Subbiah V, Hong DS, Naing A, Velez-Bravo VM, Barnes TG, Hagemeister FB, Falchook GS, Karp DD, Wheler JJ, Piha-Paul SA, Garrido-Laguna I, Shpall EJ, Fayad LE, Neelapu SS, Meric-Bernstam F, Kurzrock R, Fanale MA. Safety and Efficacy of Vorinostat Plus Sirolimus or Everolimus in Patients with Relapsed Refractory Hodgkin Lymphoma. Clin Cancer Res. 2020 Nov 1;26(21):5579-5587. Epub 2020 Oct 14. [https://doi.org/10.1158/1078-0432.ccr-20-1215 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33055173/ PubMed] NCT01087554
−
#'''UNITY-NHL:''' Fowler NH, Samaniego F, Jurczak W, Ghosh N, Derenzini E, Reeves JA, Knopińska-Posłuszny W, Cheah CY, Phillips T, Lech-Maranda E, Cheson BD, Caimi PF, Grosicki S, Leslie LA, Chavez JC, Fonseca G, Babu S, Hodson DJ, Shao SH, Burke JM, Sharman JP, Law JY, Pagel JM, Miskin HP, Sportelli P, O'Connor OA, Weiss MS, Zinzani PL. Umbralisib, a Dual PI3Kδ/CK1ε Inhibitor in Patients With Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2021 May 20;39(15):1609-1618. Epub 2021 Mar 8. [https://doi.org/10.1200/jco.20.03433 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8148421/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33683917/ PubMed] NCT02793583
+
[[Category:Hodgkin lymphoma regimens]]
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[[Category:Follicular lymphoma regimens]]
 
 
[[Category:Historical regimens]]
 
[[Category:Historical regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
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[[Category:Indolent lymphomas]]
+
[[Category:Aggressive lymphomas]]
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[[Category:Non-Hodgkin lymphomas]]
 

Revision as of 12:53, 22 January 2023

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main Hodgkin lymphoma page for current regimens.

0 regimens on this page
0 variants on this page


Untreated

ABVDm

ABVDm: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine, methylprednisolone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Le Maignan et al. 2003 (H90-NM) 1990-1996 Phase 3 (C) EBVMm Seems not superior

Chemotherapy

Glucocorticoid therapy

References

  1. H90-NM: Le Maignan C, Desablens B, Delwail V, Dib M, Berthou C, Vigier M, Ghandour C, Atmani S, Casassus P, Maisonneuve H, Le Mevel A, Traulle C, Bernard M, Briere J, Colonna P, Andrieu JM. Three cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) or epirubicin, bleomycin, vinblastine, and methotrexate (EBVM) plus extended field radiation therapy in early and intermediate Hodgkin disease: 10-year results of a randomized trial. Blood. 2004 Jan 1;103(1):58-66. Epub 2003 Aug 7. link to original article PubMed

ABVE-PC

ABVE-PC: Adriamycin (Doxorubicin), Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide


Regimen variant #2, 3 cycles with response adaptation

Study Evidence
Schwartz et al. 2009 (POG P9425) Phase 2
This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 3 cycles

Subsequent treatment

  • Rapid early responders: IFRT consolidation x 21 Gy
  • Slow early responders: ABVE-PC x 2 (5 cycles total), then IFRT consolidation x 21 Gy


Regimen variant #4, 5 cycles

Study Evidence
Schwartz et al. 2009 (POG P9425) Phase 2
This regimen is intended for pediatric patients, younger than 22 years old, who are slow early responders. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.

Preceding treatment

  • ABVE-PC x 3, with slow early response

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 5 cycles, including the first 3 cycles

Subsequent treatment

  • IFRT consolidation x 21 Gy

References

  1. POG P9425: Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. Epub 2009 Jul 7. Erratum: in Blood 2016 128:605 link to original article contains dosing details in manuscript link to PMC article PubMed NCT00005578

BCVPP

BCVPP: BCNU (Carmustine), Cyclophosphamide, Vincristine, Procarbazine, Prednisone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Durant et al. 1978 1971-1975 Non-randomized portion of RCT
Bakemeier et al. 1984 1972-1976 Phase 3 (E-esc) MOPP Seems not superior1

1For patients achieving CR, this regimen seemed to have comparatively superior survival.

Chemotherapy

Glucocorticoid therapy

References

  1. Durant JR, Gams RA, Velez-Garcia E, Bartolucci A, Wirtschafter D, Dorfman R. BCNU, velban, cyclophosphamide, procarbazine, and prednisone (BVCPP) in advanced Hodgkin's disease. Cancer. 1978 Nov;42(5):2101-10. link to original article PubMed
  2. Bakemeier RF, Anderson JR, Costello W, Rosner G, Horton J, Glick JH, Hines JD, Berard CW, DeVita VT Jr; ECOG. BCVPP chemotherapy for advanced Hodgkin's disease: evidence for greater duration of complete remission, greater survival, and less toxicity than with a MOPP regimen: results of the Eastern Cooperative Oncology Group study. Ann Intern Med. 1984 Oct;101(4):447-56. link to original article PubMed

ChlVPP/PABIOE

ChlVPP/PABIOE: Chlorambucil, Vinblastine, Procarbazine, Prednisone alternating with Prednisolone, Adriamycin (Doxorubicin), Bleomycin, Oncovin (Vincristine), Etoposide

Protocol

Study Years of enrollment Evidence Comparator Comparative Efficacy
Hancock et al. 2001 1992-1996 Randomized (C) PABIOE Superior OS

Chemotherapy, ChlVPP portion

Glucocorticoid therapy, ChlVPP portion

Glucocorticoid therapy, PABIOE portion

Chemotherapy, PABIOE portion

References

  1. Hancock BW, Gregory WM, Cullen MH, Hudson GV, Burton A, Selby P, Maclennan KA, Jack A, Bessell EM, Smith P, Linch DC; British National Lymphoma Investigation; Central Lymphoma Group. ChlVPP alternating with PABlOE is superior to PABlOE alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation/Central Lymphoma Group randomized controlled trial. Br J Cancer. 2001 May 18;84(10):1293-300. link to orginal article link to PMC article PubMed
  2. UKLG LY09: Johnson PW, Radford JA, Cullen MH, Sydes MR, Walewski J, Jack AS, MacLennan KA, Stenning SP, Clawson S, Smith P, Ryder D, Hancock BW; United Kingdom Lymphoma Group. Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol. 2005 Dec 20;23(36):9208-18. Epub 2005 Nov 28. link to original article contains dosing details in manuscript PubMed ISRCTN97144519
    1. Subgroup analysis: Johnson PW, Sydes MR, Hancock BW, Cullen M, Radford JA, Stenning SP. Consolidation radiotherapy in patients with advanced Hodgkin's lymphoma: survival data from the UKLG LY09 randomized controlled trial (ISRCTN97144519). J Clin Oncol. 2010 Jul 10;28(20):3352-9. Epub 2010 May 24. link to original article PubMed

COMP

COMP: Cyclophosphamide, Oncovin (Vincristine), Methotrexate, Prednisone

Regimen

Study Evidence
Moxley et al. 1967 Pilot

Chemotherapy

Glucocorticoid therapy

References

  1. Moxley JH 3rd, De Vita VT, Brace K, Frei E 3rd. Intensive combination chemotherapy and X-irradiation in Hodgkin's disease. Cancer Res. 1967 Jul;27(7):1258-63. link to original article PubMed

COPP (CCNU)

COPP: CCNU (Lomustine), Oncovin (Vincristine), Procarbazine, Prednisone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cooper et al. 1980 1972-1975 Phase 3 (E-switch-ic) 1. CVPP Seems not superior
2. MOPP Seems not superior
3. MVPP Seems not superior

Chemotherapy

Glucocorticoid therapy

References

  1. Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. link to original article PubMed

COPP/ABVD

COPP/ABVD: Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone alternating with Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
C-MOPP/ABVD: CyclophosphaMide, Oncovin (Vincristine), Procarbazine, Prednisone alternating with Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Protocol variant #1, 4 cycles

Study Years of enrollment Evidence Comparator Comparative Efficacy
Sieber et al. 2002 (GHSG HD5) 1988-1993 Phase 3 (C) COPP/ABV/IMEP Seems not superior
Sieber et al. 2004 (GHSG HD6) 1988-1993 Phase 3 (C) COPP/ABV/IMEP Seems not superior
Engert et al. 2003 (GHSG HD8) 1993-1998 Non-randomized portion of RCT

Chemotherapy, COPP portion

Glucocorticoid therapy, COPP portion

28-day cycle for 2 total cycles of COPP, alternating with 2 total cycles of ABVD

Chemotherapy, ABVD portion

28-day cycle for 2 total cycles of ABVD, alternating with 2 total cycles of COPP

Subsequent treatment


Protocol variant #2, 6 cycles

Study Evidence
Diehl et al. 1995 (GHSG HD3) Non-randomized portion of RCT

Chemotherapy, COPP portion

Glucocorticoid therapy, COPP portion

28-day cycle for 3 total cycles of COPP, alternating with 3 total cycles of ABVD

Chemotherapy, ABVD portion

28-day cycle for 3 total cycles of ABVD, alternating with 3 total cycles of COPP

Subsequent treatment

  • COPP/ABVD x 1 (8 cycles total) versus IFRT


Protocol variant #3, 10 cycles

Study Years of enrollment Evidence Comparator Comparative Efficacy
Takenaka et al. 2000 (JCOG 8905) 1989-1993 Phase 2
Diehl et al. 1998 (GHSG HD9) 1993-1998 Phase 3 (C) 1. BEACOPP
2. eBEACOPP 		Seems to have inferior OS
Ballova et al. 2005 (GHSG HD9elderly) 1993-1998 Phase 3 (C) BEACOPP Seems not superior

Chemotherapy, COPP portion

Glucocorticoid therapy, COPP portion

Chemotherapy, ABVD portion

  • Doxorubicin (Adriamycin) as follows:
    • Cycles 2, 4, 6, 8, 10: 25 mg/m2 IV once per day on days 1 & 15
  • Bleomycin (Blenoxane) as follows:
    • Cycles 2, 4, 6, 8, 10: 9 mg/m2 (maximum dose of 15 mg) IV once per day on days 1 & 15
  • Vinblastine (Velban) as follows:
    • Cycles 2, 4, 6, 8, 10: 6 mg/m2 (maximum dose of 10 mg) IV once per day on days 1 & 15
  • Dacarbazine (DTIC) as follows:
    • Cycles 2, 4, 6, 8, 10: 250 mg/m2 IV once per day on days 1 & 15

28-day cycle for 10 cycles

Subsequent treatment

  • Some studies: IFRT x 30 Gy after completion of chemotherapy was given to patients with bulky (at least 10 cm maximum diameter) disease

Dose modifications

  • Treatment was postponed for at least 1 week or until recovery if:
    • Pretreatment ANC was less than 1500/uL
    • Platelet count was less than 100 x 109/L
    • AST/S-GOT was greater than 100 IU/L
    • Total bilirubin was greater than 2
  • Vincristine and vinblastine were temporarily discontinued if patients had grade 2 or greater neurotoxicity (e.g. motor weakness, paresthesia, constipation)
  • Doxorubicin was discontinued if cardiac LV ejection fraction was less than 50%
  • Bleomycin was stopped if the PaO2 was less than 70 mmHg or if it decreased more than 10 mmHg from the previous measurement
  • Note: Dacarbazine 250 mg/m2 was used at this dose reduction based on experiences in a pilot study in which there was severe emesis with 375 mg/m2.

References

  1. GHSG HD3: Diehl V, Loeffler M, Pfreundschuh M, Ruehl U, Hasenclever D, Nisters-Backes H, Sieber M, Smith K, Tesch H, Geilen W, Adler M, Bartels H, Brandenburg U, Diezler P, Doelken G, Enzian J, Fuchs R, Gassmann W, Gerhartz H, Hagenaukamp U, Hecht T, Hiller E, Hinkelbein H, Lathan B, Kirchner H, Kuehn G, Kuerten H, Loos U, Makoski B, Oertel W, Petsch S, Pfab R, Pflueger H, Planker M, Rohioff R, Sack H, Samandari S, Sauer R, Schalk K, Schmitz G, Schoppe W, Schwieder G, Szepesi S, Teichmann J, Wilhelmy W, Worst P, Fischer R, Georgii A, Huebner E, Schwarze EW; German Hodgkin's Study Group. Further chemotherapy versus low-dose involved-field radiotherapy as consolidation of complete remission after six cycles of alternating chemotherapy in patients with advance Hodgkin's disease. Ann Oncol. 1995 Nov;6(9):901-10. link to original article PubMed
  2. GHSG HD9: Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Rueffer JU, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duehmke E, Georgii A, Loeffler M. BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 1998 Dec;16(12):3810-21. link to original articlecontains dosing details in manuscript PubMed
    1. Update: Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dörken B, Müller-Hermelink HK, Dühmke E, Loeffler M; German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12;348(24):2386-95. link to original articlecontains dosing details in abstract PubMed
    2. Update: Engert A, Diehl V, Franklin J, Lohri A, Dörken B, Ludwig WD, Koch P, Hänel M, Pfreundschuh M, Wilhelm M, Trümper L, Aulitzky WE, Bentz M, Rummel M, Sezer O, Müller-Hermelink HK, Hasenclever D, Löffler M. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009 Sep 20;27(27):4548-54. link to original article PubMed
    3. Pooled update: von Tresckow B, Kreissl S, Dipl-Math HG, Bröckelmann PJ, Pabst T, Fridrik M, Rummel M, Jung W, Thiemer J, Sasse S, Bürkle C, Baues C, Diehl V, Engert A, Borchmann P; German Hodgkin Study Group. Intensive treatment strategies in advanced-stage Hodgkin's lymphoma (HD9 and HD12): analysis of long-term survival in two randomised trials. Lancet Haematol. 2018 Oct 01;5(10):e462-73. link to original article PubMed
  3. JCOG 8905: Takenaka T, Mikuni C, Miura A, Sasaki T, Suzuki H, Hotta T, Hirano M, Fukuhara S, Sugiyama H, Nasu K, Dohi H, Kozuru M, Tomonaga M, Tajima K, Niimi M, Fukuda H, Mukai K, Shimoyama M; Lymphoma Study Group of the Japan Clinical Oncology Group. Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). Jpn J Clin Oncol. 2000 Mar;30(3):146-52. link to original article contains dosing details in abstract PubMed
  4. GHSG HD5: Sieber M, Tesch H, Pfistner B, Rueffer U, Lathan B, Brosteanu O, Paulus U, Koch T, Pfreundschuh M, Loeffler M, Engert A, Josting A, Wolf J, Hasenclever D, Franklin J, Duehmke E, Georgii A, Schalk KP, Kirchner H, Doelken G, Munker R, Koch P, Herrmann R, Greil R, Anselmo AP, Diehl V. Rapidly alternating COPP/ABV/IMEP is not superior to conventional alternating COPP/ABVD in combination with extended-field radiotherapy in intermediate-stage Hodgkin's lymphoma: final results of the German Hodgkin's Lymphoma Study Group Trial HD5. J Clin Oncol. 2002 Jan 15;20(2):476-84. link to original article PubMed
  5. GHSG HD8: Engert A, Schiller P, Josting A, Herrmann R, Koch P, Sieber M, Boissevain F, De Wit M, Mezger J, Duhmke E, Willich N, Muller RP, Schmidt BF, Renner H, Muller-Hermelink HK, Pfistner B, Wolf J, Hasenclever D, Loffler M, Diehl V; German Hodgkin's Lymphoma Study Group. Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2003 Oct 1;21(19):3601-8. Epub 2003 Aug 11. link to original article contains dosing details in abstract PubMed
    1. Update: Sasse S, Klimm B, Görgen H, Fuchs M, Heyden-Honerkamp A, Lohri A, Koch O, Wilhelm M, Trenn G, Finke J, Müller RP, Diehl V, Eich HT, Borchmann P, Engert A; German Hodgkin Study Group (GHSG). Comparing long-term toxicity and efficacy of combined modality treatment including extended- or involved-field radiotherapy in early-stage Hodgkin's lymphoma. Ann Oncol. 2012 Nov;23(11):2953-9. Epub 2012 Jul 5. link to original article PubMed
    2. Update: Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, Buerkle C, Borchmann S, Fuchs M, Borchmann P, Diehl V, Engert A. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017 Jun 20;35(18):1999-2007. Epub 2017 Apr 18. link to original article PubMed
  6. GHSG HD6: Sieber M, Tesch H, Pfistner B, Rueffer U, Paulus U, Munker R, Hermann R, Doelken G, Koch P, Oertel J, Roller S, Worst P, Bischof H, Glunz A, Greil R, von Kalle K, Schalk KP, Hasenclever D, Brosteanu O, Duehmke E, Georgii A, Engert A, Loeffler M, Diehl V, Mueller RP, Willich N, Fischer R, Hansmann ML, Stein H, Schober T, Koch B; German Hodgkin's Lymphoma Study Group. Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial. Ann Oncol. 2004 Feb;15(2):276-82. link to original article PubMed
  7. GHSG HD9elderly: Ballova V, Rüffer JU, Haverkamp H, Pfistner B, Müller-Hermelink HK, Dühmke E, Worst P, Wilhelmy M, Naumann R, Hentrich M, Eich HT, Josting A, Löffler M, Diehl V, Engert A. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005 Jan;16(1):124-31. link to original articlecontains dosing details in abstract PubMed

CVPP

CVPP: CCNU (Lomustine), Vinblastine, Procarbazine, Prednisone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cooper et al. 1980 1972-1975 Phase 3 (E-switch-ic) 1. COPP Seems not superior
2. MOPP Seems to have superior CR rate
3. MVPP Seems not superior
Pavlovsky et al. 1988 1977-1986 Randomized (E-de-esc) CVPP & RT Inferior FFS1
Pavlovsky et al. 1997 1986-NR Randomized (C) AOPE Seems to have superior CR rate
Sackmann-Muriel et al. 1997 1987-1994 Randomized (C) AOPE Seems to have superior EFS

1No advantage was seen for either arm in the favorable prognosis group, whereas this arm had inferior DFS for the unfavorable prognosis group.

Chemotherapy

Glucocorticoid therapy

References

  1. Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. link to original article PubMed
  2. Pavlovsky S, Maschio M, Santarelli MT, Sackmann Muriel F, Corrado C, Garcia I, Schwartz L, Montero C, Lobo Sanahuja F, Magnasco O, Raha R, Cavagnaro F. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage I-II Hodgkin's disease. J Natl Cancer Inst. 1988 Nov 16;80(18):1466-73. link to original article PubMed
    1. Update: Pavlovsky S, Santarelli MT, Sackmann Muriel F, Fernández I, Garcia I, Schwartz L, Montero C, Sanahuja FL, Magnasco H, Costa A, Corrado C, Raha R, Bezares R. Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage III-IV A & B Hodgkin's disease. Ann Oncol. 1992 Jul;3(7):533-7. link to original article PubMed
  3. Pavlovsky S, Schvartzman E, Lastiri F, Magnasco H, Corrado C, Raslawski E, Cancela ME, Ardaiz MC, Cerutti I, Rosso A, Bruno S, Aranguren PN, Salvarezza A, Donato H, Dibar E, Zirone S; GATLA. Randomized trial of CVPP for three versus six cycles in favorable-prognosis and CVPP versus AOPE plus radiotherapy in intermediate-prognosis untreated Hodgkin's disease. J Clin Oncol. 1997 Jul;15(7):2652-8. link to original article PubMed
  4. Sackmann-Muriel F, Zubizarreta P, Gallo G, Scopinaro M, Alderete D, Alfaro E, Casak S, Chantada G, Felice MS, Quinteros R. Hodgkin disease in children: results of a prospective randomized trial in a single institution in Argentina. Med Pediatr Oncol. 1997 Dec;29(6):544-52. link to original article PubMed

Doxorubicin & Vinblastine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Press et al. 2001 (SWOG S9133) 1992-2000 Phase 3 (E-esc) STLI Superior PFS

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

28-day cycle for 3 cycles

Subsequent treatment

  • STLI

References

  1. SWOG S9133: Press OW, LeBlanc M, Lichter AS, Grogan TM, Unger JM, Wasserman TH, Gaynor ER, Peterson BA, Miller TP, Fisher RI. Phase III randomized intergroup trial of subtotal lymphoid irradiation versus doxorubicin, vinblastine, and subtotal lymphoid irradiation for stage IA to IIA Hodgkin's disease. J Clin Oncol. 2001 Nov 15;19(22):4238-44. link to original article contains dosing details in manuscript PubMed NCT00002495

LOPP

LOPP: Leukeran (Chlorambucil), Oncovin (Vincristine), Procarbazine, Prednisone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Hancock 1986 1979-NR Randomized (E-switch-ic) MOPP Seems not superior
Hancock et al. 1992 1983-1989 Randomized (C) LOPP/EVAP Seems to have inferior OS

Chemotherapy

Glucocorticoid therapy

References

  1. Hancock BW; British National Lymphoma Investigation. Randomised study of MOPP (mustine, Oncovin, procarbazine, prednisone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease. Radiother Oncol. 1986 Nov;7(3):215-21. link to original article PubMed
    1. Update: Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Haybittle JL, Bennett MH, MacLennan KA, Jelliffe AM; BNLI. British National Lymphoma Investigation randomised study of MOPP (mustine, Oncovin, procarbazine, prednisolone) against LOPP (Leukeran substituted for mustine) in advanced Hodgkin's disease--long term results. Br J Cancer. 1991 Apr;63(4):579-82. link to original article link to PMC article PubMed
  2. Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Bennett MH, MacLennan KA, Haybittle JL, Anderson L, Linch DC; BNLI. LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial. J Clin Oncol. 1992 Aug;10(8):1252-8. link to original article PubMed

LOPP/EVAP

LOPP/EVAP: Leukeran (Chlorambucil), Oncovin (Vincristine), Procarbazine, Prednisone alternating with Etoposide, Vinblastine, Adriamycin (Doxorubicin), Prednisone

Protocol

Study Years of enrollment Evidence Comparator Comparative Efficacy
Hancock et al. 1992 1983-1989 Randomized (E-switch-ic) LOPP Seems to have superior OS
Hancock et al. 1994 1990-1991 Randomized (C) LOPP-EVA Superior CR rate

Chemotherapy, LOPP portion

Glucocorticoid therapy, LOPP portion

Chemotherapy, EVAP portion

Glucocorticoid therapy, EVAP portion

References

  1. Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Bennett MH, MacLennan KA, Haybittle JL, Anderson L, Linch DC; BNLI. LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial. J Clin Oncol. 1992 Aug;10(8):1252-8. link to original article PubMed
  2. Hancock BW, Vaughan Hudson G, Vaughan Hudson B, Linch DC, Anderson L, MacLennan KA; BNLI. Hybrid LOPP/EVA is not better than LOPP alternating with EVAP: a prematurely terminated British National Lymphoma Investigation randomized trial. Ann Oncol. 1994;5 Suppl 2:117-20. link to original article PubMed

Mechlorethamine monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Goodman et al. 1946 NR Non-randomized
Jacobson et al. 1946 1943-1945 Non-randomized
Wintrobe et al. 1947 NR Non-randomized
Meyer & Overmiller 1949 1946-1947 Non-randomized
Jacobs et al. 1968 1960-1963 Randomized (C) Cyclophosphamide Seems not superior

These references are of major historic interest as they are the first systemic chemotherapy trials in humans. Note that some of these early trials used nitrogen mustards other than mechlorethamine but are grouped here for simplicity.

Chemotherapy

References

  1. Goodman LS, Wintrobe MM, Dameshek W, Goodman MJ, Gilman A, McLennan MT. Nitrogen mustard therapy; use of methyl-bis (beta-chloroethyl) amine hydrochloride and tris (beta-chloroethyl) amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders. J Am Med Assoc. 1946 Sep 21;132:126-32. link to original article PubMed
  2. Jacobson LO, Spurr CL, Guzman-Barron ES, Smith T, Lushbaugh C, Dick GF. Nitrogen mustard therapy; studies on the effect of methyl-bis (beta-chloroethyl) amine hydrochloride on neoplastic diseases and allied disorders of the hemopoietic system. J Am Med Assoc. 1946 Oct 5;132:263-71. link to original article PubMed
  3. Wintrobe MM, Huguley CM Jr, McLennan MT, Penna de Carvalho Lima L. Nitrogen mustard as a therapeutic agent for Hodgkin's disease, lymphosarcoma and leukemia. Ann Intern Med. 1947 Oct;27(4):529-40. link to original article PubMed
  4. Meyer AH, Overmiller WC. The use of nitrogen mustard in Hodgkin's disease and lymphosarcoma. Ann Intern Med. 1949 Feb;30(2):381-6. link to original article PubMed
  5. Jacobs EM, Peters FC, Luce JK, Zippin C, Wood DA. Mechlorethamine HCl and cyclophosphamide in the treatment of Hodgkin's disease and the lymphomas. JAMA. 1968 Feb 5;203(6):392-8. link to original article PubMed

MOPP/ABVD

MOPP/ABVD: Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone alternating with Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Protocol

Study Years of enrollment Evidence Comparator Comparative Efficacy
Santoro et al. 1982 1974-1980 Phase 3 (E-switch-ic) MOPP Superior PFS
Somers et al. 1994 1981-1986 Phase 3 (E-switch-ic) MOPP Seems to have superior FFS
Canellos et al. 1992 (CALGB 8251) 1982-NR Phase 3 (E-switch-ic) 1. ABVD Seems not superior1
2. MOPP Seems to have superior EFS1
Viviani et al. 1996 1982-1990 Phase 3 (C) MOPP-ABVD Seems not superior
Connor et al. 1997 (NCIC-CTG HD4) 1984-1989 Phase 3 (C) MOPP-ABV Seems not superior
Hutchinson et al. 1998 (CCG-521) 1986-1990 Phase 3 (C) ABVD, then RT Might have inferior EFS

1Reported efficacy for CALGB 8251 is based on the 2009 update.

Chemotherapy, MOPP portion

Glucocorticoid therapy, MOPP portion

Chemotherapy, ABVD portion

References

  1. Santoro A, Bonadonna G, Bonfante V, Valagussa P. Alternating drug combinations in the treatment of advanced Hodgkin's disease. N Engl J Med. 1982 Apr 1;306(13):770-5. link to original article PubMed
    1. Update: Bonadonna G, Valagussa P, Santoro A. Alternating non-cross-resistant combination chemotherapy or MOPP in stage IV Hodgkin's disease: a report of 8-year results. Ann Intern Med. 1986 Jun;104(6):739-46. link to original article PubMed
  2. CALGB 8251: Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992 Nov 19;327(21):1478-84. link to original article PubMed
    1. Update: Canellos GP, Niedzwiecki D. Long-term follow-up of Hodgkin's disease trial. N Engl J Med. 2002 May 2;346(18):1417-8. link to original article PubMed
    2. Update: Canellos GP, Niedzwiecki D, Johnson JL. Long-term follow-up of survival in Hodgkin's lymphoma. N Engl J Med. 2009 Dec 10;361(24):2390-1. link to original article PubMed
  3. Somers R, Carde P, Henry-Amar M, Tarayre M, Thomas J, Hagenbeek A, Monconduit M, de Pauw BE, Breed WP, Verdonck L, Burgers JMV, Eghbali H, Zittoun R; EORTC. A randomized study in stage IIIB and IV Hodgkin's disease comparing eight courses of MOPP versus an alteration of MOPP with ABVD: a European Organisation for Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie controlled clinical trial. J Clin Oncol. 1994 Feb;12(2):279-87. link to original article PubMed
  4. Viviani S, Bonadonna G, Santoro A, Bonfante V, Zanini M, Devizzi L, Soncini F, Valagussa P. Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin's disease: ten-year results. J Clin Oncol. 1996 May;14(5):1421-30. link to original article PubMed
  5. NCIC-CTG HD4: Connors JM, Klimo P, Adams G, Burns BF, Cooper I, Meyer RM, O'Reilly SE, Pater J, Quirt I, Sadura A, Shustik C, Skillings J, Sutcliffe S, Verma S, Yoshida S, Zee B. Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group. J Clin Oncol. 1997 Apr;15(4):1638-45. Erratum in: J Clin Oncol 1997 Jul;15(7):2762. link to original article PubMed
  6. CCG-521: Hutchinson RJ, Fryer CJ, Davis PC, Nachman J, Krailo MD, O'Brien RT, Collins RD, Whalen T, Reardon D, Trigg ME, Gilchrist GS. MOPP or radiation in addition to ABVD in the treatment of pathologically staged advanced Hodgkin's disease in children: results of the Children's Cancer Group Phase III Trial. J Clin Oncol. 1998 Mar;16(3):897-906. link to original article PubMed

MVPP

MVPP: Mechlorethamine, Vinblastine, Procarbazine, Prednisone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cooper et al. 1980 1972-1975 Phase 3 (E-switch-ic) 1. COPP Seems not superior
2. CVPP Seems not superior
3. MOPP Seems not superior

Chemotherapy

Glucocorticoid therapy

References

  1. Cooper MR, Pajak TF, Nissen NI, Stutzman L, Brunner K, Cuttner J, Falkson G, Grunwald H, Bank A, Leone L, Seligman BR, Silver RT, Weiss RB, Haurani F, Blom J, Spurr CL, Glidewell OJ, Gottlieb AJ, Holland JF. A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease. Cancer. 1980 Aug 15;46(4):654-62. link to original article PubMed

NOVP

NOVP: Novantrone (Mitoxantrone), Oncovin (Vincristine), Vinblastine, Prednisone

Regimen

Study Evidence
Hagemeister et al. 1990 Phase 2

Chemotherapy

Glucocorticoid therapy

References

  1. Hagemeister FB, Cabanillas F, Velásquez WS, Meistrich ML, Liang JC, McLaughlin P, Redman JR, Romaguera JE, Rodríguez MA, Swan F Jr, Fuller LM. NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease. Semin Oncol. 1990 Dec;17(6 Suppl 10):34-8. link to original article PubMed

SCAB

SCAB: Streptozocin, CCNU (Lomustine), Adriamycin (Doxorubicin), Bleomycin

Regimen

Study Evidence
Diggs et al. 1981 Non-randomized

Chemotherapy

References

  1. Diggs CH, Wiernik PH, Sutherland JC. Treatment of advanced untreated Hodgkin's disease with SCAB--an alternative to MOPP. Cancer. 1981 Jan 15;47(2):224-8. link to original article PubMed
    1. Update: Wiernik PH, Schiffer CA. Long-term follow-up of advanced Hodgkin's disease patients treated with a combination of streptozotocin, lomustine (CCNU), doxorubicin and bleomycin (SCAB). J Cancer Res Clin Oncol. 1988;114(1):105-7. link to original article PubMed

Vinblastine monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Stutzman et al. 1966 1963-1964 Randomized (E-switch-ic) Cyclophosphamide Superior ORR

Chemotherapy

References

  1. Stutzman L, Ezdinli EZ, Stutzman MA. Vinblastine sulfate vs cyclophosphamide in the therapy for lymphoma. JAMA. 1966 Jan 17;195(3):173-8. link to original article PubMed

OPPA

OPPA: Oncovin (Vincristine), Procarbazine, Prednisone, Adriamycin (Doxorubicin)

Regimen

Study Years of enrollment Evidence
Mauz-Körholz et al. 2010 (GPOH-HD-2002) 2002-2005 Phase II

This regimen is meant for girls. Patients with early-stage disease only received the OPPA portion, see text for details.

Chemotherapy

Glucocorticoid therapy

28-day cycle for 2 cycles

Subsequent treatment

  • Treatment group 2: COPP x 2
  • Treatment group 3: COPP x 4

References

  1. GPOH-HD-2002: Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. link to original article contains dosing details in manuscript PubMed NCT00416832

VAMP (Methotrexate)

VAMP: Vinblastine, Adriamycin (Doxorubicin), Methrotrexate, Prednisone

Regimen

Study Evidence
Metzger et al. 2012 (HOD99) Phase 2

To be completed? This is to be distinguished from the VAMP protocols used in AML and multiple myeloma.

Chemotherapy

Glucocorticoid therapy

4 cycles

Subsequent treatment

References

  1. HOD99: Metzger ML, Weinstein HJ, Hudson MM, Billett AL, Larsen EC, Friedmann A, Howard SC, Donaldson SS, Krasin MJ, Kun LE, Marcus KJ, Yock TI, Tarbell N, Billups CA, Wu J, Link MP. Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma. JAMA. 2012 Jun 27;307(24):2609-16. link to original article link to PMC article PubMed

ABVE

ABVE: Adriamycin (Doxorubicin), Bleomycin, Vincristine, Etoposide

Regimen

Study Years of enrollment Evidence
Tebbi et al. 2012 (POG P9426) 1996-2001 Non-randomized (see note)

Note: this trial had a randomization to receive or not receive dexrazoxane. Labeled here as non-randomized because this drug does not have antineoplastic properties.

Chemotherapy

Supportive therapy

  • Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 6 to 14, then once per day on days 16 until ANC greater than 1000/uL

28-day cycle for 2 cycles

Subsequent treatment

  • CR: IFRT consolidation
  • Other than CR: ABVE x 2, then IFRT consolidation

References

  1. POG P9426: Tebbi CK, Mendenhall NP, London WB, Williams JL, Hutchison RE, Fitzgerald TJ, de Alarcón PA, Schwartz C, Chauvenet A. Response-dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2012 Dec 15;59(7):1259-65. Epub 2012 Aug 21. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00002827

MOPP

MOPP: Mechlorethamine, Oncovin (Vincristine), Procarbazine, Prednisone


Regimen variant #3, uncapped vincristine

Study Years of enrollment Evidence
Young et al. 1973a 1964-NR Non-randomized (RT)
Kolygin 1976 1970-1975 Non-randomized (RT)

Chemotherapy

Glucocorticoid therapy

28-day cycle for 6 to 8 cycles

References

  1. Young RC, DeVita VT, Johnson RE. Hodgkin's disease in childhood. Blood. 1973 Aug;42(2):163-74. link to original article PubMed
  2. Kolygin BA. Combination chemotherapy of Hodgkin's disease in children. Cancer. 1976 Oct;38(4):1494-7. link to original article PubMed

Consolidation after upfront therapy

C-MOPP

C-MOPP: CyclophosphaMide, Oncovin (Vincristine), Procarbazine, Prednisone
COPP: Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone

Regimen variant #1, 2 cycles

Study Years of enrollment Evidence
Mauz-Körholz et al. 2010 (GPOH-HD-2002) 2002-2005 Phase 2

Preceding treatment

Chemotherapy

Glucocorticoid therapy

28-day cycle for 2 cycles


Regimen variant #2, 4 cycles

Study Years of enrollment Evidence
Mauz-Körholz et al. 2010 (GPOH-HD-2002) 2002-2005 Phase 2

Preceding treatment

Chemotherapy

Glucocorticoid therapy

28-day cycle for 4 cycles

References

  1. GPOH-HD-2002: Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. link to original article contains dosing details in manuscript PubMed NCT00416832

COPDAC

COPDAC: Cyclophosphamide, Oncovin (Vincristine), Prednisone, DACarbazine

Regimen variant #1, 2 cycles

Study Years of enrollment Evidence
Mauz-Körholz et al. 2010 (GPOH-HD-2002) 2002-2005 Phase 2

Preceding treatment

Chemotherapy

Glucocorticoid therapy

28-day cycle for 2 cycles


Regimen variant #2, 4 cycles

Study Years of enrollment Evidence
Mauz-Körholz et al. 2010 (GPOH-HD-2002) 2002-2005 Phase 2

Preceding treatment

Chemotherapy

Glucocorticoid therapy

28-day cycle for 4 cycles

References

  1. GPOH-HD-2002: Mauz-Körholz C, Hasenclever D, Dörffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlén J, Bergsträsser E, Fosså A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Körholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. Epub 2010 Jul 12. link to original article contains dosing details in manuscript PubMed NCT00416832

Maintenance after upfront therapy

Bacillus Calmette-Guérin (BCG) monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Sokal et al. 1974 1965-1967 Randomized, <20 pts in this subgroup (E-esc) Observation Superior PFS

Note: this study was open to patients with "malignant lymphoma" but the majority had Hodgkin disease.

Immunotherapy

References

  1. Sokal JE, Aungst CW, Snyderman M. Delay in progression of malignant lymphoma after BCG vaccination. N Engl J Med. 1974 Dec 5;291(23):1226-30. link to original article PubMed

Relapsed or refractory, salvage therapy

ABDIC

ABDIC: Adriamycin (Doxorubicin), Bleomycin, DIC (Dacarbazine), CCNU (Lomustine), Prednisone

Regimen

Study Evidence
Rodgers et al. 1980 Phase 2

Chemotherapy

Glucocorticoid therapy

References

  1. Rodgers RW, Gamble JF, Loh KK, Shullenberger CC. Adriamycin, bleomycin, DIC, CCNU, and prednisone (ABDIC) chemotherapy in MOPP-resistant Hodgkin's disease. Cancer. 1980 Dec 1;46(11):2349-55. link to original article PubMed
    1. Update: Tannir N, Hagemeister F, Velasquez W, Cabanillas F. Long-term follow-up with ABDIC salvage chemotherapy of MOPP-resistant Hodgkin's disease. J Clin Oncol. 1983 Jul;1(7):432-9. link to original article PubMed

ABVD

ABVD: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Regimen

Study Evidence
Krikorian et al. 1978 Phase 2
Santoro & Bonadonna 1979 Non-randomized
Santoro et al. 1982a Non-randomized
Harker et al. 1984 Non-randomized

This is for historical interest only; ABVD is no longer used in the salvage setting.

Chemotherapy

References

  1. Krikorian JG, Portlock CS, Rosenberg SA. Treatment of advanced Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) after failure of MOPP therapy. Cancer. 1978 Jun;41(6):2107-11. link to original article PubMed
  2. Santoro A, Bonadonna G. Prolonged disease-free survival in MOPP-resistant Hodgkin's disease after treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). Cancer Chemother Pharmacol. 1979;2(2):101-5. link to original article PubMed
  3. Santoro A, Bonfante V, Bonadonna G. Salvage chemotherapy with ABVD in MOPP-resistant Hodgkin's disease. Ann Intern Med. 1982 Feb;96(2):139-43. link to original article PubMed
  4. Harker WG, Kushlan P, Rosenberg SA. Combination chemotherapy for advanced Hodgkin's disease after failure of MOPP: ABVD and B-CAVe. Ann Intern Med. 1984 Oct;101(4):440-6. link to original article PubMed

B-CAVe

B-CAVe: Bleomycin, CCNU (Lomustine), Adriamycin (Doxorubicin), Vinblastine

Regimen

Study Evidence
Porzig et al. 1978 Non-randomized
Harker et al. 1984 Non-randomized

Chemotherapy

References

  1. Porzig KJ, Portlock CS, Robertson A, Rosenberg SA. Treatment of advanced Hodgkin's disease with B-CAVE following MOPP failure. Cancer. 1978 May;41(5):1670-5. link to original article PubMed
  2. Harker WG, Kushlan P, Rosenberg SA. Combination chemotherapy for advanced Hodgkin's disease after failure of MOPP: ABVD and B-CAVe. Ann Intern Med. 1984 Oct;101(4):440-6. link to original article PubMed

BVCPP

BVCPP: BCNU (Carmustine), Vinblastine, Cyclophosphamide, Procarbazine, Prednisone

Regimen

Study Years of enrollment Evidence
Durant et al. 1978 1971-1975 Non-randomized portion of RCT

Chemotherapy

Glucocorticoid therapy

Subsequent treatment

  • Patients who achieved CR: No additional therapy versus MOPP x 6 versus BVCPP x 6 additional cycles

References

  1. Durant JR, Gams RA, Velez-Garcia E, Bartolucci A, Wirtschafter D, Dorfman R. BCNU, velban, cyclophosphamide, procarbazine, and prednisone (BVCPP) in advanced Hodgkin's disease. Cancer. 1978 Nov;42(5):2101-10. link to original article PubMed

BVDS

BVDS: Bleomycin, Vinblastine, Doxorubicin, Streptozocin

Regimen

Study Evidence
Vinciguerra et al. 1977 Non-randomized, <20 pts

Chemotherapy

References

  1. Vinciguerra V, Coleman M, Jarowski CI, Degnan TJ, Silver RT. A new combination chemotherapy for resistant Hodgkin disease. JAMA. 1977 Jan 3;237(1):33-5. link to original article PubMed

CEP

CEP: CCNU (Lomustine), Etoposide, Prednimustine

Regimen

Study Evidence
Santoro et al. 1986 Non-randomized

Chemotherapy

References

  1. Santoro A, Viviani S, Valagussa P, Bonfante V, Bonadonna G. CCNU, etoposide, and prednimustine (CEP) in refractory Hodgkin's disease. Semin Oncol. 1986 Mar;13(1 Suppl 1):23-6. PubMed

CVB

CVB: CCNU (Lomustine), Vinblastine, Bleomycin

Regimen

Study Evidence
Goldman & Dawson 1975 Non-randomized

Chemotherapy

References

  1. Goldman JM, Dawson AA. Combination therapy for advanced resistant Hodgkin's disease. Lancet. 1975 Dec 20;2(7947):1224-7. link to original article PubMed

CVPP

CVPP: CCNU (Lomustine), Vinblastine, Procarbazine, Prednisone

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Vinciguerra et al. 1986 1975-1981 Randomized (C) 1. ABOS
2. CVPP/ABOS 		Seems not superior

Chemotherapy

Glucocorticoid therapy

References

  1. Vinciguerra V, Propert KJ, Coleman M, Anderson JR, Stutzman L, Pajak TF, Nissen NI, Frizzera G, Gottlieb A, Holland JF; CALGB. Alternating cycles of combination chemotherapy for patients with recurrent Hodgkin's disease following radiotherapy: a prospectively randomized study by the Cancer and Leukemia Group B. J Clin Oncol. 1986 Jun;4(6):838-46. link to original article PubMed

SCAB

SCAB: Streptozocin, CCNU (Lomustine), Adriamycin (Doxorubicin), Bleomycin

Regimen

Study Evidence
Levi et al. 1977 Non-randomized, <20 pts

Chemotherapy

References

  1. Levi JA, Wiernik PH, Diggs CH. Combination chemotherapy of advanced previously treated Hodgkin's disease with streptozotocin, CCNU, adriamycin and bleomycin. Med Pediatr Oncol. 1977;3(1):33-40. link to original article PubMed

Relapsed or refractory, further lines of therapy

Carmustine monotherapy

Regimen

Study Evidence
Young et al. 1971 Non-randomized

Chemotherapy

References

  1. Young RC, DeVita VT Jr, Serpick AA, Canellos GP. Treatment of advanced Hodgkin's disease with (1,3 bis (2-chloroethyl)-1-nitrosourea) BCNU. N Engl J Med. 1971 Aug 26;285(9):475-9. link to original article PubMed

Doxorubicin & Lomustine

Regimen

Study Evidence
Williams & Einhorn 1977 Non-randomized, <20 pts

Chemotherapy

References

  1. Williams SD, Einhorn LH. Combination chemotherapy with doxorubicin and lomustine: treatment of refractory Hodgkin's disease. JAMA. 1977 Oct 10;238(15):1659-61. link to original article PubMed

Panobinostat monotherapy

Regimen

Study Years of enrollment Evidence Efficacy
Younes et al. 2012 (CLBH589E2214) 2008-2009 Phase 2 Investigator assessment: 27%
Central review: 22%

Patients had progressed after auto HSCT and had a median of 4 prior systemic regimens (range 2 to 7).

Targeted therapy

21-day cycles

References

  1. CLBH589E2214: Younes A, Sureda A, Ben-Yehuda D, Zinzani PL, Ong TC, Prince HM, Harrison SJ, Kirschbaum M, Johnston P, Gallagher J, Le Corre C, Shen A, Engert A. Panobinostat in patients with relapsed/refractory Hodgkin's lymphoma after autologous stem-cell transplantation: results of a phase II study. J Clin Oncol. 2012 Jun 20;30(18):2197-203. Epub 2012 Apr 30. link to original article contains dosing details in manuscript PubMed NCT00742027

Sirolimus & Vorinostat

Regimen

Study Years of enrollment Evidence
Janku et al. 2020 (MDACC 2009-0729) 2010-2015 Non-randomized

This is a very heavily pre-treated cohort, median of 6 prior therapies; doses here are one level below MTD and are proposed as the ongoing doses to be studied.

Immunosuppressive therapy

Targeted therapy

  • Vorinostat (Zolinza) as follows:
    • Cycle 1: 300 mg PO once per day on days 7 to 28
    • Subsequent cycles: 300 mg PO once per day on days 1 to 28

28-day cycles

References

  1. MDACC 2009-0729: Janku F, Park H, Call SG, Madwani K, Oki Y, Subbiah V, Hong DS, Naing A, Velez-Bravo VM, Barnes TG, Hagemeister FB, Falchook GS, Karp DD, Wheler JJ, Piha-Paul SA, Garrido-Laguna I, Shpall EJ, Fayad LE, Neelapu SS, Meric-Bernstam F, Kurzrock R, Fanale MA. Safety and Efficacy of Vorinostat Plus Sirolimus or Everolimus in Patients with Relapsed Refractory Hodgkin Lymphoma. Clin Cancer Res. 2020 Nov 1;26(21):5579-5587. Epub 2020 Oct 14. link to original article PubMed NCT01087554
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