Revision as of 19:51, 12 February 2018

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81 regimens on this page 128 variants on this page

Guidelines

ESMO

Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2014) PubMed

NCCN

NCCN Guidelines - Hodgkin Lymphoma

Untreated, early-stage favorable (ESF)

Note: the definition of early stage favorable varies across organizations, e.g., EORTC, GHSG, NCIC, and NCCN; see original definitions used in the trials for details.

ABVD

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

Example orders

Example orders for ABVD in Hodgkin lymphoma

Regimen #1, 2 cycles

Study	Evidence	Comparator	Efficacy
Engert et al. 2007 (GHSG HD7)	Phase III	No chemotherapy	Superior FFTF
Engert et al. 2010 (GHSG HD10)	Phase III	ABVD x 4	Seems not superior
Behringer et al. 2014 (GHSG HD13)	Phase III	ABV	Superior FFTF
		AV	Superior FFTF
		AVD	Might have superior FFTF

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

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 2 cycles

Subsequent treatment

GHSG HD7: EFRT
GHSG HD10: IFRT x 20 Gy versus IFRT x 30 Gy
GHSG HD13: IFRT x 30 Gy

Regimen #2, 2 cycles with response adaptation

Study	Evidence	Comparator	Efficacy
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10 F)	Phase III	See link	See link

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

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 2 cycles

Subsequent treatment

Negative interim PET-CT (1 or 2 points on the 5-point Deauville scale): 2 more cycles of ABVD (4 cycles total) versus 1 more cycle of ABVD, then INRT
- Positive PET-CT: eBEACOPP, then INRT

Regimen #3, 3 cycles with response adaptation

Study	Evidence
Radford et al. 2015 (UK NCRI RAPID)	Non-randomized portion of RCT

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 3 cycles

Subsequent treatment

Negative interim PET-CT (1 or 2 points on the 5-point Deauville scale): IFRT versus no further treatment
- Positive interim PET-CT: proceeded to receive a fourth cycle of ABVD, then IFRT

Regimen #4, 4 cycles

Study	Evidence	Comparator	Efficacy
Bonadonna et al. 2004	Non-randomized portion of RCT
Engert et al. 2010 (GHSG HD10)	Phase III	ABVD x 2	Seems not superior
Meyer et al. 2011 (NCIC CTG/ECOG HD.6)	Phase III	STNI	Seems to have superior OS

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 4 cycles

Subsequent treatment

Bonadonna et al. 2004: IFRT versus STNI
GHSG HD10: IFRT x 20 Gy versus IFRT x 30 Gy

References

Bonadonna G, Bonfante V, Viviani S, Di Russo A, Villani F, Valagussa P. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results. J Clin Oncol. 2004 Jul 15;22(14):2835-41. link to original article contains protocol PubMed
Engert A, Franklin J, Eich HT, Brillant C, Sehlen S, Cartoni C, Herrmann R, Pfreundschuh M, Sieber M, Tesch H, Franke A, Koch P, de Wit M, Paulus U, Hasenclever D, Loeffler M, Müller RP, Müller-Hermelink HK, Dühmke E, Diehl V. Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol. 2007 Aug 10;25(23):3495-502. link to original article contains protocol PubMed
1. 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. doi: 10.1200/JCO.2016.70.9410. Epub 2017 Apr 18. link to original article PubMed
Engert A, Plütschow A, Eich HT, Lohri A, Dörken B, Borchmann P, Berger B, Greil R, Willborn KC, Wilhelm M, Debus J, Eble MJ, Sökler M, Ho A, Rank A, Ganser A, Trümper L, Bokemeyer C, Kirchner H, Schubert J, Král Z, Fuchs M, Müller-Hermelink HK, Müller RP, Diehl V. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. 2010 Aug 12;363(7):640-52. link to original article PubMed
1. Sub-group analysis: Böll B, Goergen H, Behringer K, Bröckelmann PJ, Hitz F, Kerkhoff A, Greil R, von Tresckow B, Eichenauer DA, Bürkle C, Borchmann S, Fuchs M, Diehl V, Engert A, Borchmann P. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood. 2016 May 5;127(18):2189-92. Epub 2016 Feb 1.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. doi: 10.1200/JCO.2016.70.9410. Epub 2017 Apr 18. link to original article PubMed
Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; Eastern Cooperative Oncology Group. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2;366(5):399-408. Epub 2011 Dec 11. link to original article link to PMC article contains protocol PubMed
Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed
Behringer K, Goergen H, Hitz F, Zijlstra JM, Greil R, Markova J, Sasse S, Fuchs M, Topp MS, Soekler M, Mathas S, Meissner J, Wilhelm M, Koch P, Lindemann HW, Schalk E, Semrau R, Kriz J, Vieler T, Bentz M, Lange E, Mahlberg R, Hassler A, Vogelhuber M, Hahn D, Mezger J, Krause SW, Skoetz N, Böll B, von Tresckow B, Diehl V, Hallek M, Borchmann P, Stein H, Eich H, Engert A; German Hodgkin Study Group; Swiss Group for Clinical Cancer Research; Arbeitsgemeinschaft Medikamentöse Tumortherapie. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet. 2015 Apr 11;385(9976):1418-27. Epub 2014 Dec 22. Erratum in: Lancet. 2015 Apr 11;385(9976):1396. link to original article PubMed
1. Sub-group analysis: Böll B, Goergen H, Behringer K, Bröckelmann PJ, Hitz F, Kerkhoff A, Greil R, von Tresckow B, Eichenauer DA, Bürkle C, Borchmann S, Fuchs M, Diehl V, Engert A, Borchmann P. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood. 2016 May 5;127(18):2189-92. Epub 2016 Feb 1.link to original article PubMed
Retrospective: Stamatoullas A, Brice P, Bouabdallah R, Mareschal S, Camus V, Rahal I, Franchi P, Lanic H, Tilly H. Outcome of patients older than 60 years with classical Hodgkin lymphoma treated with front line ABVD chemotherapy: frequent pulmonary events suggest limiting the use of bleomycin in the elderly. Br J Haematol. 2015 Jul;170(2):179-84. Epub 2015 Apr 19. link to original article PubMed
Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P, Wimperis J, Culligan D, Popova B, Smith P, McMillan A, Brownell A, Kruger A, Lister A, Hoskin P, O'Doherty M, Barrington S. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015 Apr 23;372(17):1598-607. link to original article contains protocol PubMed

AVD

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AVD: Adriamycin (Doxorubicin), Vinblastine, Dacarbazine

Regimen

Study	Evidence	Comparator	Efficacy
Behringer et al. 2014 (GHSG HD13)	Phase III	ABV	Not reported
		ABVD	Might have inferior FFTF
		AV	Not reported

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 2 cycles

Subsequent treatment

IFRT x 30 Gy

References

Behringer K, Goergen H, Hitz F, Zijlstra JM, Greil R, Markova J, Sasse S, Fuchs M, Topp MS, Soekler M, Mathas S, Meissner J, Wilhelm M, Koch P, Lindemann HW, Schalk E, Semrau R, Kriz J, Vieler T, Bentz M, Lange E, Mahlberg R, Hassler A, Vogelhuber M, Hahn D, Mezger J, Krause SW, Skoetz N, Böll B, von Tresckow B, Diehl V, Hallek M, Borchmann P, Stein H, Eich H, Engert A; German Hodgkin Study Group; Swiss Group for Clinical Cancer Research; Arbeitsgemeinschaft Medikamentöse Tumortherapie. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet. 2015 Apr 11;385(9976):1418-27. Epub 2014 Dec 22. Erratum in: Lancet. 2015 Apr 11;385(9976):1396. link to original article PubMed
1. Sub-group analysis: Böll B, Goergen H, Behringer K, Bröckelmann PJ, Hitz F, Kerkhoff A, Greil R, von Tresckow B, Eichenauer DA, Bürkle C, Borchmann S, Fuchs M, Diehl V, Engert A, Borchmann P. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood. 2016 May 5;127(18):2189-92. Epub 2016 Feb 1.link to original article PubMed

MOPP-ABV

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MOPP-ABV: Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone, Adriamycin (Doxorubicin), Bleomycin, Vinblastine

Regimen

Study	Evidence	Comparator	Efficacy
Fermé et al. 2007 (EORTC-GELA H8-F)	Phase III	See link	See link

Chemotherapy

Mechlorethamine (Mustargen) 6 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose is capped at 2 mg) IV once on day 1
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 8
Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Vinblastine (Velban) 6 mg/m² IV once on day 8

28-day cycle for 3 cycles

Subsequent treatment

IFRT, 3 to 4 weeks later

References

Noordijk EM, Carde P, Dupouy N, Hagenbeek A, Krol AD, Kluin-Nelemans JC, Tirelli U, Monconduit M, Thomas J, Eghbali H, Aleman BM, Bosq J, Vovk M, Verschueren TA, Pény AM, Girinsky T, Raemaekers JM, Henry-Amar M. Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials. J Clin Oncol. 2006 Jul 1;24(19):3128-35. Epub 2006 Jun 5. link to original article PubMed
Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; EORTC-GELA H8 Trial. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. link to original article contains verified protocol in supplement PubMed

Radiation therapy

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RT: Radiation Therapy

Regimen #1, 35 Gy of subtotal nodal irradiation (STNI)

Study	Evidence	Comparator	Efficacy
Meyer et al. 2011 (NCIC CTG/ECOG HD.6)	Phase III	ABVD	Seems to have inferior OS

Radiotherapy

35 Gy in 20 fractions

Regimen #2, 36 Gy of STNI + 4 Gy boost

Study	Evidence	Comparator	Efficacy
Fermé et al. 2007 (EORTC-GELA H8-F)	Phase III	MOPP-ABV, then IFRT	Inferior OS

Radiotherapy

36 Gy in 18 fractions, with 4 Gy boost to involved fields

References

Carde P, Hagenbeek A, Hayat M, Monconduit M, Thomas J, Burgers MJ, Noordijk EM, Tanguy A, Meerwaldt JH, Le Fur R et al. Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol. 1993 Nov;11(11):2258-72. link to original article PubMed
Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; EORTC-GELA H8 Trial. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. link to original article contains verified protocol in supplement PubMed
Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; Eastern Cooperative Oncology Group. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2;366(5):399-408. Epub 2011 Dec 11. link to original article link to PMC article contains verified protocol PubMed

Stanford V

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Regimen

Study	Evidence
Advani et al. 2013 (G4)	Non-randomized

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per week on weeks 1, 3, 5, 7
Vinblastine (Velban) 6 mg/m² IV once per week on weeks 1, 3, 5, 7
Mechlorethamine (Mustargen) 6 mg/m² IV once per week on weeks 1 & 5
Etoposide (Vepesid) 60 mg/m² IV twice per week (presumably on subsequent days) on weeks 3 & 7
Vincristine (Oncovin) 1.4 mg/m² (maximum of 2mg in any individual dose) IV once per week on weeks 2, 4, 6, 8
Bleomycin (Blenoxane) 5 units/m² IV once per week on weeks 2, 4, 6, 8
Prednisone (Sterapred) 40 mg/m² PO every other day for 6 weeks, then tapered by 10 mg per day over the next 2 weeks

8-week course

Subsequent treatment

IFRT, 1 to 3 weeks later

References

Advani RH, Hoppe RT, Baer D, Mason J, Warnke R, Allen J, Daadi S, Rosenberg SA, Horning SJ. Efficacy of abbreviated Stanford V chemotherapy and involved-field radiotherapy in early-stage Hodgkin lymphoma: mature results of the G4 trial. Ann Oncol. 2013 Apr;24(4):1044-8. Epub 2012 Nov 7. contains limited protocol link to PMC article PubMed

Untreated, early-stage unfavorable (ESU)

Note: the definition of early stage unfavorable varies across organizations, e.g., EORTC, GHSG, NCIC, and NCCN; see original definitions used in the trials for details.

ABVD

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

Example orders

Example orders for ABVD in Hodgkin lymphoma

Regimen #1, 2 cycles

Study	Evidence	Comparator	Efficacy
Meyer et al. 2011 (NCIC CTG/ECOG HD.6)	Phase III	See link	See link

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.

Preceding treatment

GHSG HD14: Escalated BEACOPP x 2

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 2 cycles

Subsequent treatment

NCIC CTG/ECOG HD.6: STNI
GHSG HD14: IFRT x 30 Gy

Regimen #2, 2 cycles with response adaptation

Study	Evidence	Comparator	Efficacy
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10 U)	Phase III	See link	See link

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

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 2 cycles

Subsequent treatment

Negative interim PET-CT (1 or 2 points on the 5-point Deauville scale): 4 more cycles of ABVD versus 2 more cycles of ABVD, then INRT
Positive interim PET-CT: eBEACOPP, then INRT

Regimen #3, 4 cycles

Study	Evidence	Comparator	Efficacy
Eich et al. 2010 (GHSG HD11)	Phase III	See link	See link
Meyer et al. 2011 (NCIC CTG/ECOG HD.6)	Phase III	ABVD x 2, then STNI	Seems to have superior OS
von Tresckow et al. 2012 (GHSG HD14)	Phase III	See link	See link

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 4 cycles

Subsequent treatment

GHSG HD11: IFRT x 20 Gy versus IFRT x 30 Gy
GHSG HD14: IFRT x 30 Gy

Regimen #4, 6 to 8 cycles

Study	Evidence	Comparator	Efficacy
Advani et al. 2015 (ECOG E2496)	Phase III	Stanford V	Seems not superior

Note: this protocol gives a range of cycles.

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 6 to 8 cycles

Subsequent treatment

IFRT x 36 Gy

References

Carde P, Hagenbeek A, Hayat M, Monconduit M, Thomas J, Burgers MJ, Noordijk EM, Tanguy A, Meerwaldt JH, Le Fur R et al. Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol. 1993 Nov;11(11):2258-72. link to original article PubMed
Eich HT, Diehl V, Görgen H, Pabst T, Markova J, Debus J, Ho A, Dörken B, Rank A, Grosu AL, Wiegel T, Karstens JH, Greil R, Willich N, Schmidberger H, Döhner H, Borchmann P, Müller-Hermelink HK, Müller RP, Engert A. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010 Sep 20;28(27):4199-206. Epub 2010 Aug 16. link to original article contains verified protocol PubMed
1. 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. doi: 10.1200/JCO.2016.70.9410. Epub 2017 Apr 18. link to original article PubMed
Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; Eastern Cooperative Oncology Group. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2;366(5):399-408. Epub 2011 Dec 11. link to original article link to PMC article contains protocol PubMed
von Tresckow B, Plütschow A, Fuchs M, Klimm B, Markova J, Lohri A, Kral Z, Greil R, Topp MS, Meissner J, Zijlstra JM, Soekler M, Stein H, Eich HT, Mueller RP, Diehl V, Borchmann P, Engert A. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012 Mar 20;30(9):907-13. Epub 2012 Jan 23. link to original article contains verified protocol PubMed
Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed
Retrospective: Stamatoullas A, Brice P, Bouabdallah R, Mareschal S, Camus V, Rahal I, Franchi P, Lanic H, Tilly H. Outcome of patients older than 60 years with classical Hodgkin lymphoma treated with front line ABVD chemotherapy: frequent pulmonary events suggest limiting the use of bleomycin in the elderly. Br J Haematol. 2015 Jul;170(2):179-84. Epub 2015 Apr 19. link to original article PubMed
Subgroup analysis: Advani RH, Hong F, Fisher RI, Bartlett NL, Robinson KS, Gascoyne RD, Wagner H Jr, Stiff PJ, Cheson BD, Stewart DA, Gordon LI, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized phase III trial comparing ABVD plus radiotherapy with the Stanford V regimen in patients with stages I or II locally extensive, bulky mediastinal Hodgkin lymphoma: a subset analysis of the North American Intergroup E2496 trial. J Clin Oncol. 2015 Jun 10;33(17):1936-42. Epub 2015 Apr 20. link to original article contains limited protocol link to PMC article PubMed

A+AVD

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A+AVD: Adcetris (Brentuximab vedotin), Adriamycin (Doxorubicin), Vinblastine, Dacarbazine
BV + AVD: Brentuximab Vedotin, Adriamycin (Doxorubicin), Vinblastine, Dacarbazine

Regimen

Study	Evidence
Kumar et al. 2016	Phase II

Chemotherapy

Brentuximab vedotin (Adcetris) 1.2 mg/kg IV once per day on days 1 & 15
Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 4 cycles

Chemotherapy is followed by repeat PET-CT; patients with a negative PET-CT proceeded to receive ISRT.

References

Kumar A, Casulo C, Yahalom J, Schöder H, Barr PM, Caron P, Chiu A, Constine LS, Drullinsky P, Friedberg JW, Gerecitano JF, Hamilton A, Hamlin PA, Horwitz SM, Jacob AG, Matasar MJ, McArthur GN, McCall SJ, Moskowitz AJ, Noy A, Palomba ML, Portlock CS, Straus DJ, VanderEls N, Verwys SL, Yang J, Younes A, Zelenetz AD, Zhang Z, Moskowitz CH. Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma. Blood. 2016 Sep 15;128(11):1458-64. Epub 2016 Jul 25. link to original article contains verified protocol link to PMC article PubMed

BEACOPP

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BEACOPP: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone
BEACOPP_baseline

Example orders

Example orders for BEACOPP in Hodgkin lymphoma

Regimen

Study	Evidence	Comparator	Efficacy
Eich et al. 2010 (GHSG HD11)	Phase III	See link	See link

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

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 25 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 650 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2mg) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

21-day cycle for 4 cycles

Subsequent treatment

GHSG HD11: IFRT x 20 Gy versus IFRT x 30 Gy

References

Eich HT, Diehl V, Görgen H, Pabst T, Markova J, Debus J, Ho A, Dörken B, Rank A, Grosu AL, Wiegel T, Karstens JH, Greil R, Willich N, Schmidberger H, Döhner H, Borchmann P, Müller-Hermelink HK, Müller RP, Engert A. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010 Sep 20;28(27)99-206. Epub 2010 Aug 16. link to original article contains verified protocol PubMed
1. 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. doi: 10.1200/JCO.2016.70.9410. Epub 2017 Apr 18. link to original article PubMed

Escalated BEACOPP

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eBEACOPP: escalated Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone

Regimen

Study	Evidence	Comparator	Efficacy
von Tresckow et al. 2012 (GHSG HD14)	Phase III	See link	See link

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

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 200 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1250 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2mg per cycle) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

Supportive medications

Filgrastim (Neupogen) (dose not specified) SC once per day starting on day 8, continues until ANC greater than 1000/uL for 3 consecutive days

21-day cycle for 2 cycles

Subsequent treatment

ABVD x 2, then IFRT x 30 Gy

References

von Tresckow B, Plütschow A, Fuchs M, Klimm B, Markova J, Lohri A, Kral Z, Greil R, Topp MS, Meissner J, Zijlstra JM, Soekler M, Stein H, Eich HT, Mueller RP, Diehl V, Borchmann P, Engert A. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012 Mar 20;30(9):907-13. Epub 2012 Jan 23. link to original article contains verified protocol PubMed

MOPP-ABV

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MOPP-ABV: Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone, Adriamycin (Doxorubicin), Bleomycin, Vinblastine

Regimen #1, 4 cycles

Study	Evidence	Comparator	Efficacy
Fermé et al. 2007 (EORTC-GELA H8-U)	Phase III	See link	See link

Chemotherapy

Mechlorethamine (Mustargen) 6 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose is capped at 2 mg) IV once on day 1
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 8
Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Vinblastine (Velban) 6 mg/m² IV once on day 8

28-day cycle for 4 cycles

Subsequent treatment

IFRT versus STNI, in 3 to 4 weeks

Regimen #2, 6 cycles

Study	Evidence	Comparator	Efficacy
Fermé et al. 2007 (EORTC-GELA H8-U)	Phase III	See link	See link

Chemotherapy

Mechlorethamine (Mustargen) 6 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose is capped at 2 mg) IV once on day 1
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 8
Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Vinblastine (Velban) 6 mg/m² IV once on day 8

28-day cycle for 6 cycles

Subsequent treatment

IFRT, in 3 to 4 weeks

References

Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; EORTC-GELA H8 Trial. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. link to original article contains verified protocol in supplement PubMed

RABVD

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RABVD: Rituximab, Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Regimen

Study	Evidence
Kasamon et al. 2012	Phase II, <20 pts in subgroup

Patients were NOT required to have CD20+ disease.

Chemotherapy

Rituximab (Rituxan) as follows:
- Pre-phase: 375 mg/m² IV once one week prior to cycle 1 of ABVD
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2, 4, 6: 375 mg;m² IV once on day 1
Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 6 to 8 cycles

References

Kasamon YL, Jacene HA, Gocke CD, Swinnen LJ, Gladstone DE, Perkins B, Link BK, Popplewell LL, Habermann TM, Herman JM, Matsui WH, Jones RJ, Ambinder RF. Phase 2 study of rituximab-ABVD in classical Hodgkin lymphoma. Blood. 2012 May 3;119(18):4129-32. Epub 2012 Feb 16. link to original article contains partial protocol link to PMC article PubMed

Stanford V

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Regimen

Study	Evidence	Comparator	Efficacy
Advani et al. 2015 (ECOG E2496)	Phase III	ABVD	Seems not superior

In Advani et al. 2015 the Stanford V regimen is described as "once per week for 12 weeks." However, the regimen has previously been described as being 4-week cycles for 3 cycles (same duration, but schedule is different). Until this discrepancy is resolved, we replicate the 4-week cycle version here:

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Mechlorethamine (Mustargen) 6 mg/m² IV once on day 1
Etoposide (Vepesid) 60 mg/m² IV once per day on days 15 & 16
Vincristine (Oncovin) 1.4 mg/m² (maximum of 2mg in any individual dose) IV once per day on days 8 & 22
Bleomycin (Blenoxane) 5 units/m² IV once per day on days 8 & 22
Prednisone (Sterapred) 40 mg/m² PO every other day (with taper)

28-day cycle for 3 cycles

Subsequent treatment

IFRT x 36 Gy

References

Advani RH, Hong F, Fisher RI, Bartlett NL, Robinson KS, Gascoyne RD, Wagner H Jr, Stiff PJ, Cheson BD, Stewart DA, Gordon LI, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized phase III trial comparing ABVD plus radiotherapy with the Stanford V regimen in patients with stages I or II locally extensive, bulky mediastinal Hodgkin lymphoma: a subset analysis of the North American Intergroup E2496 trial. J Clin Oncol. 2015 Jun 10;33(17):1936-42. Epub 2015 Apr 20. link to original article contains limited protocol link to PMC article PubMed

Untreated, advanced stage

Note: the definition of advanced stage varies across organizations, e.g., EORTC, GHSG, NCIC, and NCCN; see original definitions used in the trials for details.

ABVD

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

Example orders

Example orders for ABVD in Hodgkin lymphoma

Regimen #1, 2 cycles with response adaptation

Study	Evidence
Zinzani et al. 2016 (HD0801)	Non-randomized
Press et al. 2016 (SWOG S0816)	Phase II
Johnson et al. 2016 (RATHL)	Non-randomized portion of RCT

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 2 cycles

Subsequent treatment

HD0801, negative PET-CT by Juweid's criteria: 4 more cycles of ABVD (6 total)
HD0801, positive PET-CT by Juweid's criteria: IGEV salvage
SWOG S0816, negative PET-CT by Deauville score (1 to 3): 4 more cycles of ABVD (6 total)
SWOG S0186, positive PET-CT by Deauville score (4 or 5): Escalated BEACOPP salvage
RATHL, negative PET-CT by Deauville score (1 to 3): 4 more cycles of ABVD (6 total) versus AVD x 4
RATHL, positive PET-CT by Deauville score (4 or 5): Escalated BEACOPP or BEACOPP-14 salvage, specified in advance

Regimen #2, 6 cycles

Study	Evidence	Comparator	Efficacy
Zinzani et al. 2016 (HD0801)	Non-randomized
Press et al. 2016 (SWOG S0816)	Phase II
Johnson et al. 2016 (RATHL)	Non-randomized portion of RCT
Connors et al. 2017 (ECHELON-1)	Phase III	A+AVD	Seems to have inferior modified PFS

Note: Zinzani et al. 2016 does not describe the details of radiotherapy. Note that ECHELON-1 specifies "up to" 6 cycles of therapy, but does not explain circumstance in which fewer than 6 would be given.

Preceding treatment

HD0801: ABVD x 2, with negative PET-CT by Juweid's criteria
SWOG S0186 & RATHL: ABVD x 2, with negative PET-CT by Deauville score (1 to 3)

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 6 cycles (see note)

Subsequent treatment

HD0801, with initial bulky disease: Observation versus Radiotherapy

Regimen #3, 8 cycles (ABVD₈)

Study	Evidence	Comparator	Efficacy
Bonadonna et al. 1975	Phase III	MOPP	Seems not superior
Santoro et al. 1987	Phase III	MOPP	Seems to have superior OS
Canellos et al. 1992	Phase III	MOPP	Superior FFS
Canellos et al. 1992	Phase III	MOPP/ABVD	Not reported
Hoskin et al. 2009 (UK NCRI ISRCTN 64141244)	Phase III	Stanford V	Seems not superior
Viviani et al. 2011	Phase III	Escalated BEACOPP, then BEACOPP	Seems to have inferior FFFP
Gordon et al. 2013 (E2496)	Phase III	Stanford V	Seems not superior
Mounier et al. 2014 (LYSA H34)	Phase III	Escalated BEACOPP, then BEACOPP	Might have inferior EFS
Carde et al. 2016 (EORTC 20012)	Phase III	Escalated BEACOPP, then BEACOPP	Seems not superior

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 8 cycles

References

Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C. Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer. 1975 Jul;36(1):252-9. PubMed
Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, Pagnoni AM, Bonfante V, Musumeci R, Crippa F, et al. Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol. 1987 Jan;5(1):27-37. link to original article PubMed
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
Duggan DB, Petroni GR, Johnson JL, Glick JH, Fisher RI, Connors JM, Canellos GP, Peterson BA. Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. J Clin Oncol. 2003 Feb 15;21(4):607-14. link to original article PubMed
Gobbi PG, Levis A, Chisesi T, Broglia C, Vitolo U, Stelitano C, Pavone V, Cavanna L, Santini G, Merli F, Liberati M, Baldini L, Deliliers GL, Angelucci E, Bordonaro R, Federico M; Intergruppo Italiano Linfomi. ABVD versus modified Stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate- and advanced-stage Hodgkin's lymphoma: final results of a multicenter randomized trial by the Intergruppo Italiano Linfomi. J Clin Oncol. 2005 Dec 20;23(36):9198-207. Epub 2005 Sep 19. link to original article PubMed
1. Update: Chisesi T, Bellei M, Luminari S, Montanini A, Marcheselli L, Levis A, Gobbi P, Vitolo U, Stelitano C, Pavone V, Merli F, Liberati M, Baldini L, Bordonaro R, Pesce EA, Federico M. Long-term follow-up analysis of HD9601 trial comparing ABVD versus Stanford V versus MOPP/EBV/CAD in patients with newly diagnosed advanced-stage Hodgkin's lymphoma: a study from the Intergruppo Italiano Linfomi. J Clin Oncol. 2011 Nov 10;29(32):4227-33. Epub 2011 Oct 11. link to original article PubMed
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 LY09 Trial (ISRCTN97144519). 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 PubMed
Hoskin PJ, Lowry L, Horwich A, Jack A, Mead B, Hancock BW, Smith P, Qian W, Patrick P, Popova B, Pettitt A, Cunningham D, Pettengell R, Sweetenham J, Linch D, Johnson PW. Randomized comparison of the Stanford V regimen and ABVD in the treatment of advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244. J Clin Oncol. 2009 Nov 10;27(32):5390-6. Epub 2009 Sep 8. link to original article PubMed
Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. link to original article contains verified protocol PubMed
Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Stiff PJ, Cheson BD, Gospodarowicz M, Advani R, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: An Intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013 Feb 20;31(6):684-91. Epub 2012 Nov 26. link to original article link to PMC article PubMed
1. Subgroup analysis: Evens AM, Hong F, Gordon LI, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Gospodarowicz M, Cheson BD, Stiff PJ, Advani R, Miller TP, Hoppe RT, Kahl BS, Horning SJ. The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. Br J Haematol. 2013 Apr;161(1):76-86. Epub 2013 Jan 29. link to PMC article PubMed
Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, Gabarre J, Casasnovas O, Jaubert J, Colin P, Delmer A, Devidas A, Bachy E, Nicolas-Virelizier E, Aoudjhane A, Humbrecht C, Andre M, Carde P; Lymphoma Study Association (LYSA). ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug;25(8):1622-8. Epub 2014 May 14. link to original article contains verified protocol PubMed
Retrospective: Stamatoullas A, Brice P, Bouabdallah R, Mareschal S, Camus V, Rahal I, Franchi P, Lanic H, Tilly H. Outcome of patients older than 60 years with classical Hodgkin lymphoma treated with front line ABVD chemotherapy: frequent pulmonary events suggest limiting the use of bleomycin in the elderly. Br J Haematol. 2015 Jul;170(2):179-84. Epub 2015 Apr 19. link to original article PubMed
Zinzani PL, Broccoli A, Gioia DM, Castagnoli A, Ciccone G, Evangelista A, Santoro A, Ricardi U, Bonfichi M, Brusamolino E, Rossi G, Anastasia A, Zaja F, Vitolo U, Pavone V, Pulsoni A, Rigacci L, Gaidano G, Stelitano C, Salvi F, Rusconi C, Tani M, Freilone R, Pregno P, Borsatti E, Sacchetti GM, Argnani L, Levis A. Interim positron emission tomography response-adapted therapy in advanced-stage Hodgkin lymphoma: final results of the phase II part of the HD0801 study. J Clin Oncol. 2016 Apr 20;34(12):1376-85. Epub 2016 Feb 16. link to original article contains verified protocol PubMed
Press OW, Li H, Schöder H, Straus DJ, Moskowitz CH, LeBlanc M, Rimsza LM, Bartlett NL, Evens AM, Mittra ES, LaCasce AS, Sweetenham JW, Barr PM, Fanale MA, Knopp MV, Noy A, Hsi ED, Cook JR, Lechowicz MJ, Gascoyne RD, Leonard JP, Kahl BS, Cheson BD, Fisher RI, Friedberg JW. US Intergroup Trial of response-adapted therapy for stage III to IV Hodgkin lymphoma using early interim fluorodeoxyglucose-positron emission tomography imaging: Southwest Oncology Group S0816. J Clin Oncol. 2016 Jun 10;34(17):2020-7. Epub 2016 Apr 11. link to original article contains verified protocol link to PMC article PubMed
Carde P, Karrasch M, Fortpied C, Brice P, Khaled H, Casasnovas O, Caillot D, Gaillard I, Bologna S, Ferme C, Lugtenburg PJ, Morschhauser F, Aurer I, Coiffier B, Meyer R, Seftel M, Wolf M, Glimelius B, Sureda A, Mounier N. Eight cycles of ABVD versus four cycles of BEACOPP_escalated plus four cycles of BEACOPP_baseline in stage III to IV, International Prognostic Score ≥ 3, high-risk Hodgkin lymphoma: First results of the phase III EORTC 20012 Intergroup trial. J Clin Oncol. 2016 Jun 10;34(17):2028-36. Epub 2016 Apr 25. link to original article contains verified protocol PubMed
Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A, d'Amore F, Enblad G, Franceschetto A, Fulham M, Luminari S, O'Doherty M, Patrick P, Roberts T, Sidra G, Stevens L, Smith P, Trotman J, Viney Z, Radford J, Barrington S. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. N Engl J Med. 2016 Jun 23;374(25):2419-29. link to original article link to protocol contains verified protocol in supplement link to PMC article PubMed
Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illés Á, Picardi M, Lech-Maranda E, Oki Y, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Chen R, Ramchandren R, Zinzani PL, Cunningham D, Rosta A, Josephson NC, Song E, Sachs J, Liu R, Jolin HA, Huebner D, Radford J; ECHELON-1 Study Group. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin's lymphoma. N Engl J Med. 2018 Jan 25;378(4):331-344. Epub 2017 Dec 10. link to original article contains verified protocol PubMed

ABVD, DD-DI

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ABVD, DD-DI: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine, Dose-Dense and Dose-Intense

Regimen

Study	Evidence
Russo et al. 2014	Phase II

Chemotherapy

Doxorubicin (Adriamycin) as follows:
- Cycles 1 to 4: 35 mg/m² IV once per day on days 1 & 11
- Cycles 5 & 6: 25 mg/m² IV once per day on days 1 & 11
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 11
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 11
Dacarbazine (DTIC) 375 mg/m² IV once on days 1 & 11

Supportive medications

Lenograstim (Granocyte) 263 µg SC once per day on days 6 to 8 and days 17 to 19 (6 doses per cycle)

21-day cycle for 6 cycles

References

Russo F, Corazzelli G, Frigeri F, Capobianco G, Aloj L, Volzone F, De Chiara A, Bonelli A, Gatani T, Marcacci G, Donnarumma D, Becchimanzi C, de Lutio E, Ionna F, De Filippi R, Lastoria S, Pinto A. A phase II study of dose-dense and dose-intense ABVD (ABVD(DD-DI) ) without consolidation radiotherapy in patients with advanced Hodgkin lymphoma. Br J Haematol. 2014 Jul;166(1):118-29. Epub 2014 Mar 27. link to original article contains verified protocol PubMed

AVD

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AVD: Adriamycin (Doxorubicin), Vinblastine, Dacarbazine

Regimen

Study	Evidence	Comparator	Efficacy
Johnson et al. 2016 (RATHL)	Phase III	ABVD	Inconclusive whether non-inferior

Preceding treatment

ABVD x 2

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 4 cycles

References

Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A, d'Amore F, Enblad G, Franceschetto A, Fulham M, Luminari S, O'Doherty M, Patrick P, Roberts T, Sidra G, Stevens L, Smith P, Trotman J, Viney Z, Radford J, Barrington S. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. N Engl J Med. 2016 Jun 23;374(25):2419-29. link to original article link to protocol contains verified protocol in supplement link to PMC article PubMed

A+AVD

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A+AVD: Adcetris (Brentuximab vedotin), Adriamycin (Doxorubicin), Vinblastine, Dacarbazine
B-AVD: Brentuximab vedotin, Adriamycin (Doxorubicin), Vinblastine, Dacarbazine
AVD-A: Adriamycin (Doxorubicin), Vinblastine, Dacarbazine, Adcetris (Brentuximab vedotin)

Regimen

Study	Evidence	Comparator	Efficacy
Younes et al. 2013	Non-randomized
Connors et al. 2017 (ECHELON-1)	Phase III	ABVD	Seems to have superior modified PFS

Younes et al. 2013 was a phase I trial but had greater than 20 patients in the MTD expansion cohort.

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15
Brentuximab vedotin (Adcetris) 1.2 mg/kg IV once per day on days 1 & 15, within "about" 1 hour of AVD infusion completion

28-day cycle for up to 6 cycles

Subsequent treatment

Younes et al. 2013: Consolidative radiotherapy was permitted at the investigator's discretion

References

Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013 Dec;14(13):1348-56. Epub 2013 Nov 15. link to original article contains verified protocol PubMed
1. Update: Connors JM, Ansell SM, Fanale M, Park SI, Younes A. Five-year follow-up of brentuximab vedotin combined with ABVD or AVD for advanced-stage classical Hodgkin lymphoma. Blood. 2017 Sep 14;130(11):1375-1377. Epub 2017 Jul 21. link to original article PubMed
Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illés Á, Picardi M, Lech-Maranda E, Oki Y, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Chen R, Ramchandren R, Zinzani PL, Cunningham D, Rosta A, Josephson NC, Song E, Sachs J, Liu R, Jolin HA, Huebner D, Radford J; ECHELON-1 Study Group. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin's lymphoma. N Engl J Med. 2018 Jan 25;378(4):331-344. Epub 2017 Dec 10. link to original article contains verified protocol PubMed

BEACOPP

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BEACOPP: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone

Example orders

Example orders for BEACOPP in Hodgkin lymphoma

Regimen #1, 4 cycles

Study	Evidence	Comparator	Efficacy
Viviani et al. 2011	Phase III	See link	See link
Borchmann et al. 2011 (GHSG HD12)	Phase III	See link	See link
Mounier et al. 2014 (LYSA H34)	Phase III	See link	See link
Carde et al. 2016 (EORTC 20012)	Phase III	See link	See link

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.

Preceding treatment

Escalated BEACOPP x 4

Chemotherapy

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 25 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 650 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

Supportive medications

Filgrastim (Neupogen) 300 mcg SC once per day starting day 8, continues until ANC greater than 1000/uL for 3 consecutive days (Viviani et al. 2011) or until day 14 (LYSA H34)

21-day cycle for 4 cycles

Subsequent treatment

GHSG HD12 patients with initial bulky or residual disease: ISRT x 30 Gy versus no further treatment

Regimen #2, 8 cycles

Study	Evidence	Comparator	Efficacy
Diehl et al. 1997	Non-randomized
Diehl et al. 1998 (GHSG HD9)	Phase III	Escalated dose BEACOPP	Inferior FFTF
Diehl et al. 1998 (GHSG HD9)	Phase III	COPP/ABVD	Seems to have superior OS

Note that this is technically "BEACOPP II." The original "BEACOPP I" is detailed in Diehl et al. 1997 but is of historical interest, only.

Chemotherapy

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 25 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 650 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

21-day cycle for 8 cycles

References

Diehl V, Sieber M, Rüffer U, Lathan B, Hasenclever D, Pfreundschuh M, Loeffler M, Lieberz D, Koch P, Adler M, Tesch H. BEACOPP: an intensified chemotherapy regimen in advanced Hodgkin's disease. The German Hodgkin's Lymphoma Study Group. Ann Oncol. 1997 Feb;8(2):143-8. link to original article contains verified protocol PubMed
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 verified protocol 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 protocol 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
Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. link to original article contains verified protocol PubMed
Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD, Eich HT, Mueller-Hermelink HK, Kanz L, Greil R, Rank A, Paulus U, Smardova L, Huber C, Dörken B, Nerl C, Krause SW, Mueller RP, Fuchs M, Engert A. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011 Nov 10;29(32):4234-42. Epub 2011 Oct 11. link to original article PubMed
Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, Gabarre J, Casasnovas O, Jaubert J, Colin P, Delmer A, Devidas A, Bachy E, Nicolas-Virelizier E, Aoudjhane A, Humbrecht C, Andre M, Carde P; Lymphoma Study Association (LYSA). ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug;25(8):1622-8. Epub 2014 May 14. link to original article contains verified protocol PubMed
Carde P, Karrasch M, Fortpied C, Brice P, Khaled H, Casasnovas O, Caillot D, Gaillard I, Bologna S, Ferme C, Lugtenburg PJ, Morschhauser F, Aurer I, Coiffier B, Meyer R, Seftel M, Wolf M, Glimelius B, Sureda A, Mounier N. Eight cycles of ABVD versus four cycles of BEACOPP_escalated plus four cycles of BEACOPP_baseline in stage III to IV, International Prognostic Score ≥ 3, high-risk Hodgkin lymphoma: First results of the phase III EORTC 20012 Intergroup trial. J Clin Oncol. 2016 Jun 10;34(17):2028-36. Epub 2016 Apr 25. link to original article contains verified protocol PubMed

BEACOPP-14

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BEACOPP-14: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone, 14-day course

Regimen

Study	Evidence	Comparator	Efficacy
Sieber et al. 2003	Phase II
Engert et al. 2012 (GHSG HD15)	Phase III	Escalated BEACOPP x 8	Not reported
Engert et al. 2012 (GHSG HD15)	Phase III	Escalated BEACOPP x 6	Non-inferior FFTF

Chemotherapy

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 25 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 650 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 80 mg/m² PO once per day on days 1 to 7

Supportive medications

Filgrastim (Neupogen) as follows:
- <75 kg body weight: 300 mcg SC once per day on days 8 to 13
- greater than or equal to 75 kg body weight: 480 mcg SC once per day on days 8 to 13

14-day cycle for 8 cycles

References

Sieber M, Bredenfeld H, Josting A, Reineke T, Rueffer U, Koch T, Naumann R, Boissevain F, Koch P, Worst P, Soekler M, Eich H, Müller-Hermelink HK, Franklin J, Paulus U, Wolf J, Engert A, Diehl V; German Hodgkin's Lymphoma Study Group. 14-day variant of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone regimen in advanced-stage Hodgkin's lymphoma: results of a pilot study of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2003 May 1;21(9):1734-9. link to original article contains verified protocol PubMed
Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A, Zijlstra J, Král Z, Fuchs M, Hallek M, Kanz L, Döhner H, Dörken B, Engel N, Topp M, Klutmann S, Amthauer H, Bockisch A, Kluge R, Kratochwil C, Schober O, Greil R, Andreesen R, Kneba M, Pfreundschuh M, Stein H, Eich HT, Müller RP, Dietlein M, Borchmann P, Diehl V; German Hodgkin Study Group; Swiss Group for Clinical Cancer Research; Arbeitsgemeinschaft Medikamentöse Tumortherapie. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012 May 12;379(9828):1791-9. Epub 2012 Apr 4. Erratum in: Lancet. 2012 May 12;379(9828):1790. link to original article PubMed

C-MOPP/ABV

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C-MOPP: CyclophosphaMide, Oncovin (Vincristine), Procarbazine, Prednisone
ABV: Adriamycin (Doxorubicin), Bleomycin, Vinblastine

Regimen

Study	Evidence
Montoto et al. 2000	Phase II

Chemotherapy

Cyclophosphamide (Cytoxan) 650 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 3 mg) IV once on day 1
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 8
Bleomycin (Blenoxane) 10 mg/m² IV once on day 8
Vinblastine (Velban) 6 mg/m² IV once on day 8

28-day cycle for 8 cycles

25 to 40 Gy of radiation therapy given over extended fields (mantle or inverted "Y" type) to patients with bulky disease or ones with residual disease after completion of chemotherapy

References

Montoto S, Camós M, López-Guillermo A, Bosch F, Cervantes F, Blandé J, Esteve J, Cobo F, Nomdedeu B, Campo E, Montserrat E. Hybrid chemotherapy consisting of cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (C-MOPP/ABV) as first-line treatment for patients with advanced Hodgkin disease. Cancer. 2000 May 1;88(9):2142-8. link to original article contains protocol PubMed]

Escalated BEACOPP

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eBEACOPP: escalated Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone

Example orders

Example orders for escalated dose BEACOPP in Hodgkin lymphoma

Regimen #1, 2 cycles with response adaptation

!Study	Evidence
Borchmann et al. 2017 (GHSG HD18)	Non-randomized portion of RCT

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

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 200 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1200 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

21-day cycle for 2 cycles

Subsequent treatment

PET-negative, prior to June 2011: eBEACOPP x 6 (total) versus eBEACOPP x 8 (total)
PET-negative, after June 2011: eBEACOPP x 4 (total) versus eBEACOPP x 6 (total)
PET-positive, prior to June 2011: eBEACOPP x 8 (total) versus R-eBEACOPP x 8 (total)
PET-positive, after June 2011: eBEACOPP x 6 (total)

Regimen #2, 4 cycles

Study	Evidence	Comparator	Efficacy
Viviani et al. 2011	Phase III	See link	See link
Borchmann et al. 2011 (GHSG HD12)	Phase III	See link	See link
Mounier et al. 2014 (LYSA H34)	Phase III	See link	See link
Carde et al. 2016 (EORTC 20012)	Phase III	See link	See link
Borchmann et al. 2017 (GHSG HD18)	Phase III	eBEACOPP x 6 eBEACOPP x 8	Non-inferior PFS (*)

Note: except for GHSG HD18, this is a component of a sequential treatment protocol. Efficacy for GHSG HD18 is based on the 2017 update.

Chemotherapy

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 200 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1200 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

Supportive medications

Filgrastim (Neupogen) 300 mcg SC once per day starting day 8, continues until ANC greater than 1000/uL for 3 consecutive days (Viviani et al. 2011) or until day 14 (LYSA H34)

21-day cycle for 4 cycles

Subsequent treatment

All except GHSG HD18: BEACOPP x 4

Regimen #3, 6 cycles

Study	Evidence	Comparator	Efficacy
Engert et al. 2012 (GHSG HD15)	Phase III	BEACOPP-14	Non-inferior FFTF
Engert et al. 2012 (GHSG HD15)	Phase III	Escalated BEACOPP x 8	Seems to have superior OS
Borchmann et al. 2017 (GHSG HD18)	Phase III	eBEACOPP x 4 eBEACOPP x 8	Non-inferior PFS (*)

Details are not available in the abstracts; it is assumed that the regimen is identical to escalated BEACOPP x 8, with 2 fewer cycles. Efficacy for GHSG HD18 is based on the 2017 update.

Chemotherapy

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 200 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1200 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

21-day cycle for 6 cycles

Regimen #4, 8 cycles

Study	Evidence	Comparator	Efficacy
Diehl et al. 1998 (GHSG HD9)	Phase III	BEACOPP	Superior FFTF
Diehl et al. 1998 (GHSG HD9)	Phase III	COPP/ABVD	Seems to have superior OS
Borchmann et al. 2011 (GHSG HD12)	Phase III	See link	See link
Engert et al. 2012 (GHSG HD15)	Phase III	BEACOPP-14	Not reported
Engert et al. 2012 (GHSG HD15)	Phase III	Escalated BEACOPP x 6	Seems to have inferior OS
Borchmann et al. 2017 (GHSG HD18)	Phase III	eBEACOPP x 4 eBEACOPP x 6	Non-inferior PFS (*)

Efficacy for GHSG HD18 is based on the 2017 update.

Chemotherapy

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 200 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1200 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

21-day cycle for 8 cycles

Subsequent treatment

GHSG HD12 patients with initial bulky or residual disease: ISRT x 30 Gy versus no further treatment

References

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 verified protocol 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 protocol 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
Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. link to original article contains verified protocol PubMed
Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD, Eich HT, Mueller-Hermelink HK, Kanz L, Greil R, Rank A, Paulus U, Smardova L, Huber C, Dörken B, Nerl C, Krause SW, Mueller RP, Fuchs M, Engert A. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011 Nov 10;29(32):4234-42. Epub 2011 Oct 11. link to original article PubMed
Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A, Zijlstra J, Král Z, Fuchs M, Hallek M, Kanz L, Döhner H, Dörken B, Engel N, Topp M, Klutmann S, Amthauer H, Bockisch A, Kluge R, Kratochwil C, Schober O, Greil R, Andreesen R, Kneba M, Pfreundschuh M, Stein H, Eich HT, Müller RP, Dietlein M, Borchmann P, Diehl V; German Hodgkin Study Group; Swiss Group for Clinical Cancer Research; Arbeitsgemeinschaft Medikamentöse Tumortherapie. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012 May 12;379(9828):1791-9. Epub 2012 Apr 4. Erratum in: Lancet. 2012 May 12;379(9828):1790. link to original article PubMed
Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, Gabarre J, Casasnovas O, Jaubert J, Colin P, Delmer A, Devidas A, Bachy E, Nicolas-Virelizier E, Aoudjhane A, Humbrecht C, Andre M, Carde P; Lymphoma Study Association (LYSA). ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug;25(8):1622-8. Epub 2014 May 14. link to original article contains verified protocol PubMed
Carde P, Karrasch M, Fortpied C, Brice P, Khaled H, Casasnovas O, Caillot D, Gaillard I, Bologna S, Ferme C, Lugtenburg PJ, Morschhauser F, Aurer I, Coiffier B, Meyer R, Seftel M, Wolf M, Glimelius B, Sureda A, Mounier N. Eight cycles of ABVD versus four cycles of BEACOPP_escalated plus four cycles of BEACOPP_baseline in stage III to IV, International Prognostic Score ≥ 3, high-risk Hodgkin lymphoma: First results of the phase III EORTC 20012 Intergroup trial. J Clin Oncol. 2016 Jun 10;34(17):2028-36. Epub 2016 Apr 25. link to original article contains verified protocol PubMed
Borchmann P, Haverkamp H, Lohri A, Mey U, Kreissl S, Greil R, Markova J, Feuring-Buske M, Meissner J, Dührsen U, Ostermann H, Keller U, Maschmeyer G, Kuhnert G, Dietlein M, Kobe C, Eich H, Baues C, Stein H, Fuchs M, Diehl V, Engert A. Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin's lymphoma treated with BEACOPP(escalated) alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group. Lancet Oncol. 2017 Apr;18(4):454-463. Epub 2017 Feb 22. link to original article PubMed
1. Update: Borchmann P, Goergen H, Kobe C, Lohri A, Greil R, Eichenauer DA, Zijlstra JM, Markova J, Meissner J, Feuring-Buske M, Hüttmann A, Dierlamm J, Soekler M, Beck HJ, Willenbacher W, Ludwig WD, Pabst T, Topp MS, Hitz F, Bentz M, Keller UB, Kühnhardt D, Ostermann H, Schmitz N, Hertenstein B, Aulitzky W, Maschmeyer G, Vieler T, Eich H, Baues C, Stein H, Fuchs M, Kuhnert G, Diehl V, Dietlein M, Engert A. PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group. Lancet. 2017 Oct 20. [Epub ahead of print] link to original article PubMed

MOPP

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

Regimen #1, 8 cycles, prednisone 25 mg/m²

Study	Evidence	Comparator	Efficacy
Somers et al. 1994	Phase III	MOPP/ABVD	Seems to have inferior FFS

Chemotherapy

Mechlorethamine (Mustargen) 6 mg/m² IV once per day on days 1 & 8
Vincristine (Oncovin) 1.4 mg/m² (dose is capped at 2 mg) IV once per day on days 1 & 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 14
Prednisone (Sterapred) 25 mg/m² PO once per day on days 1 to 14

28-day cycle for 8 cycles

Regimen #2, capped vincristine

Study	Evidence	Comparator	Efficacy
Canellos et al. 1992	Phase III	ABVD	Inferior FFS
Canellos et al. 1992	Phase III	MOPP/ABVD	Seems to have inferior FFS

Chemotherapy

Mechlorethamine (Mustargen) 6 mg/m² IV once per day on days 1 & 8
Vincristine (Oncovin) 1.4 mg/m² (dose is capped at 2 mg) IV once per day on days 1 & 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 14
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

28-day cycle for 6 to 8 cycles

Regimen #3, uncapped vincristine

Study	Evidence	Comparator	Efficacy
Devita et al. 1970	Phase II
Bonadonna et al. 1975	Phase III	ABVD	Seems not superior
Cooper et al. 1980	Phase III	COPP	Seems not superior
		CVPP	Seems to have inferior CR rate
		MVPP	Seems not superior
Santoro et al. 1982	Phase III	MOPP/ABVD	Inferior PFS
Santoro et al. 1987	Phase III	ABVD	Seems to have inferior OS
Longo et al. 1991	Phase III	MOPP/CABS	Seems not superior

Chemotherapy

Mechlorethamine (Mustargen) 6 mg/m² IV once per day on days 1 & 8
Vincristine (Oncovin) 1.4 mg/m² IV once per day on days 1 & 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 14
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

28-day cycle for 6 to 8 cycles

References

Devita VT Jr, Serpick AA, Carbone PP. Combination chemotherapy in the treatment of advanced Hodgkin's disease. Ann Intern Med. 1970 Dec;73(6):881-95. link to original article contains protocol PubMed content property of HemOnc.org
Bonadonna G, Zucali R, Monfardini S, De Lena M, Uslenghi C. Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP. Cancer. 1975 Jul;36(1):252-9. link to original article 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. link to original article PubMed
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
Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, Pagnoni AM, Bonfante V, Musumeci R, Crippa F, et al. Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol. 1987 Jan;5(1):27-37. link to original article PubMed
Longo DL, Duffey PL, DeVita VT Jr, Wiernik PH, Hubbard SM, Phares JC, Bastian AW, Jaffe ES, Young RC. Treatment of advanced-stage Hodgkin's disease: alternating noncrossresistant MOPP/CABS is not superior to MOPP. J Clin Oncol. 1991 Aug;9(8):1409-20. link to original article PubMed
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 does not contain protocol PubMed
Somers R, Carde P, Henry-Amar M, Tarayre M, Thomas J, Hagenbeek A, Monconduit M, de Pauw BE, Breed WP, Verdonck L, et al. 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 Organization 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 contains verified protocol PubMed

MOPP-ABV

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MOPP-ABV: Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone, Adriamycin (Doxorubicin), Bleomycin, Vinblastine

Regimen

Study	Evidence	Comparator	Efficacy
Klimo et al. 1985	Phase II
Glick et al. 1998	Phase III	MOPP, then ABVD	Seems to have superior OS
Duggan et al. 2003	Phase III	ABVD	Seems not superior

Chemotherapy

Mechlorethamine (Mustargen) 6 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 8
Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Vinblastine (Velban) 6 mg/m² IV once on day 8

28-day cycle for 6 to 8 cycles

References

Klimo P, Connors JM. MOPP/ABV hybrid program: combination chemotherapy based on early introduction of seven effective drugs for advanced Hodgkin's disease. J Clin Oncol. 1985 Sep;3(9):1174-82. link to original article contains verified protocol PubMed
Glick JH, Young ML, Harrington D, Schilsky RL, Beck T, Neiman R, Fisher RI, Peterson BA, Oken MM. MOPP/ABV hybrid chemotherapy for advanced Hodgkin's disease significantly improves failure-free and overall survival: the 8-year results of the intergroup trial. J Clin Oncol. 1998 Jan;16(1):19-26. link to original article PubMed
Duggan DB, Petroni GR, Johnson JL, Glick JH, Fisher RI, Connors JM, Canellos GP, Peterson BA. Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. J Clin Oncol. 2003 Feb 15;21(4):607-14. link to original article PubMed

MOPP/ABVD

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

Regimen

Study	Evidence	Comparator	Efficacy
Santoro et al. 1982	Phase III	MOPP	Superior PFS
Canellos et al. 1992	Phase III	ABVD	Not reported
Canellos et al. 1992	Phase III	MOPP	Seems to have superior FFS
Somers et al. 1994	Phase III	MOPP	Seems to have superior FFS

To be completed

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. 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
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
Somers R, Carde P, Henry-Amar M, Tarayre M, Thomas J, Hagenbeek A, Monconduit M, de Pauw BE, Breed WP, Verdonck L, et al. 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 Organization 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
Salvagno L, Sorarù M, Sotti G, Aversa S, Chiarion Sileni V, Mazzarotto R, Scarzello G, Bianco A, Pappagallo GL, Fiorentino MV. Hybrid MOPP/ABVD and radiotherapy in advanced Hodgkin's disease. Ann Oncol. 1995 Feb;6(2):173-9. link to original article 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. link to original article PubMed
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
Longo DL, Glatstein E, Duffey PL, Young RC, Ihde DC, Bastian AW, Wilson WH, Wittes RE, Jaffe ES, Hubbard SM, DeVita VT Jr. Alternating MOPP and ABVD chemotherapy plus mantle-field radiation therapy in patients with massive mediastinal Hodgkin's disease. J Clin Oncol. 1997 Nov;15(11):3338-46. link to original article PubMed

RABVD

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RABVD: Rituximab, Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine

Regimen #1

Study	Evidence
Younes et al. 2012	Phase II

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per week x 6 weeks
Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 6 cycles (except rituximab, which is given for a total of 6 doses)

Regimen #2

Study	Evidence
Kasamon et al. 2012	Phase II

Chemotherapy

Rituximab (Rituxan) as follows:
- Pre-phase: 375 mg/m² IV once one week prior to cycle 1 of ABVD
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2, 4, 6: 375 mg;m² IV once on day 1
Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 6 to 8 cycles

References

Younes A, Oki Y, McLaughlin P, Copeland AR, Goy A, Pro B, Feng L, Yuan Y, Chuang HH, Macapinlac HA, Hagemeister F, Romaguera J, Samaniego F, Fanale MA, Dabaja BS, Rodriguez MA, Dang N, Kwak LW, Neelapu SS, Fayad LE. Phase 2 study of rituximab plus ABVD in patients with newly diagnosed classical Hodgkin lymphoma. Blood. 2012 May 3;119(18):4123-8. Epub 2012 Feb 27. link to original article contains protocol link to PMC article PubMed
Kasamon YL, Jacene HA, Gocke CD, Swinnen LJ, Gladstone DE, Perkins B, Link BK, Popplewell LL, Habermann TM, Herman JM, Matsui WH, Jones RJ, Ambinder RF. Phase 2 study of rituximab-ABVD in classical Hodgkin lymphoma. Blood. 2012 May 3;119(18):4129-32. Epub 2012 Feb 16. link to original article contains partial protocol link to PMC article PubMed

Stanford V

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Regimen

Study	Evidence	Comparator	Efficacy
Hoskin et al. 2009 (UK NCRI ISRCTN 64141244)	Phase III	ABVD	Seems not superior
Gordon et al. 2013 (ECOG E2496)	Phase III	ABVD	Seems not superior

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
- Patients older than 50: Cycle 3 doses reduced to 4 mg/m² per dose
Mechlorethamine (Mustargen) 6 mg/m² IV once on day 1
Etoposide (Vepesid) 60 mg/m² IV once per day on days 15 & 16
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once per day on days 8 & 22
- Patients older than 50: Cycle 3 doses reduced to 1 mg per dose
Bleomycin (Blenoxane) 5 units/m² IV once per day on days 8 & 22
Prednisone (Sterapred) as follows:
- Cycles 1 & 2: 40 mg/m² PO every other day
- Cycle 3, week 1 (week 9): 40 mg/m² PO every other day
- Cycle 3, week 2 (week 10): 30 mg/m² PO every other day
- Cycle 3, week 3 (week 11): 20 mg/m² PO every other day
- Cycle 3, week 4 (week 12): 10 mg/m² PO every other day

Supportive medications

If dose reduction or delay occurred at any time during chemotherapy, Filgrastim (Neupogen) 5 mcg/kg SC once per day x 5 days (starting 48 hours after myelosuppressive chemotherapy) should be given after all subsequent day 1 and 15 doses of chemotherapy. It was not precisely specified when to discontinue filgrastim.
Ranitidine (Zantac) 150 mg PO BID throughout the course of treatment
Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID throughout the course of treatment
Acyclovir (Zovirax) 200 mg PO TID throughout the course of treatment
Ketoconazole (Nizoral) 200 mg PO once per day throughout the course of treatment; note: this may be optional--Horning SJ et al. J Clin Oncol (2000) listed this as a prophylactic medication, but Horning SJ et al. J Clin Oncol (2002) did not list this when prophylactic medications were specifically listed.

28-day cycle for 3 cycles

Radiotherapy

36 Gy of consolidative radiation (1.8 Gy in 20 fractions) is started 2 to 4 weeks after chemotherapy is complete and is given to sites of disease greater than or equal to 5 cm and/or to macroscopic nodules in the spleen.

Dose reductions

Doses of Doxorubicin (Adriamycin), Vinblastine (Velban), Mechlorethamine (Mustargen), and Etoposide (Vepesid) were reduced to 65% of the original dose if the ANC on the day of treatment was 500 to 1000/uL. If ANC was less than 500/uL on the day of treatment, therapy was delayed for 1 week, and therapy resumed the following week at the dose indicated by the ANC. As noted above, Filgrastim (Neupogen) was incorporated into all subsequent treatments if there were any dose reductions or delays.

References

Bartlett NL, Rosenberg SA, Hoppe RT, Hancock SL, Horning SJ. Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage Hodgkin's disease: a preliminary report. J Clin Oncol. 1995 May;13(5):1080-8. link to original article PubMed
1. Update: Horning SJ, Hoppe RT, Breslin S, Bartlett NL, Brown BW, Rosenberg SA. Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial. J Clin Oncol. 2002 Feb 1;20(3):630-7. link to original article PubMed
Horning SJ, Williams J, Bartlett NL, Bennett JM, Hoppe RT, Neuberg D, Cassileth P. Assessment of the Stanford V regimen and consolidative radiotherapy for bulky and advanced Hodgkin's disease: Eastern Cooperative Oncology Group pilot study E1492. J Clin Oncol. 2000 Mar;18(5):972-80. link to original article PubMed
Gobbi PG, Levis A, Chisesi T, Broglia C, Vitolo U, Stelitano C, Pavone V, Cavanna L, Santini G, Merli F, Liberati M, Baldini L, Deliliers GL, Angelucci E, Bordonaro R, Federico M; Intergruppo Italiano Linfomi. ABVD versus modified Stanford V versus MOPPEBVCAD with optional and limited radiotherapy in intermediate- and advanced-stage Hodgkin's lymphoma: final results of a multicenter randomized trial by the Intergruppo Italiano Linfomi. J Clin Oncol. 2005 Dec 20;23(36):9198-207. Epub 2005 Sep 19. link to original article PubMed
1. Update: Chisesi T, Bellei M, Luminari S, Montanini A, Marcheselli L, Levis A, Gobbi P, Vitolo U, Stelitano C, Pavone V, Merli F, Liberati M, Baldini L, Bordonaro R, Pesce EA, Federico M. Long-term follow-up analysis of HD9601 trial comparing ABVD versus Stanford V versus MOPP/EBV/CAD in patients with newly diagnosed advanced-stage Hodgkin's lymphoma: a study from the Intergruppo Italiano Linfomi. J Clin Oncol. 2011 Nov 10;29(32):4227-33. Epub 2011 Oct 11. link to original article PubMed
Hoskin PJ, Lowry L, Horwich A, Jack A, Mead B, Hancock BW, Smith P, Qian W, Patrick P, Popova B, Pettitt A, Cunningham D, Pettengell R, Sweetenham J, Linch D, Johnson PW. Randomized comparison of the Stanford V regimen and ABVD in the treatment of advanced Hodgkin's Lymphoma: United Kingdom National Cancer Research Institute Lymphoma Group Study ISRCTN 64141244. J Clin Oncol. 2009 Nov 10;27(32):5390-6. Epub 2009 Sep 8. link to original article PubMed
Edwards-Bennett SM, Jacks LM, Moskowitz CH, Wu EJ, Zhang Z, Noy A, Portlock CS, Straus DJ, Zelenetz AD, Yahalom J. Stanford V program for locally extensive and advanced Hodgkin lymphoma: the Memorial Sloan-Kettering Cancer Center experience. Ann Oncol. 2010 Mar;21(3):574-81. link to original article PubMed
Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Stiff PJ, Cheson BD, Gospodarowicz M, Advani R, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: An Intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013 Feb 20;31(6):684-91. Epub 2012 Nov 26. link to original article link to PMC article PubMed
1. Subgroup analysis: Evens AM, Hong F, Gordon LI, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Gospodarowicz M, Cheson BD, Stiff PJ, Advani R, Miller TP, Hoppe RT, Kahl BS, Horning SJ. The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. Br J Haematol. 2013 Apr;161(1):76-86. Epub 2013 Jan 29. link to PMC article PubMed

VEBEP

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VEBEP: Vepesid (Etoposide), Epirubicin, Bleomycin, Endoxan (Cyclophosphamide), Prednisolone

Regimen

Study	Evidence
Viviani et al. 1999	Phase II

To be completed

Chemotherapy

References

Viviani S, Bonfante V, Santoro A, Zanini M, Devizzi L, Di Russo AD, Soncini F, Villani F, Ragni G, Valagussa P, Bonadonna G. Long-term results of an intensive regimen: VEBEP plus involved-field radiotherapy in advanced Hodgkin's disease. Cancer J Sci Am. 1999 Sep-Oct;5(5):275-82. PubMed
Picardi M, De Renzo A, Pane F, Nicolai E, Pacelli R, Salvatore M, Rotoli B. Randomized comparison of consolidation radiation versus observation in bulky Hodgkin's lymphoma with post-chemotherapy negative positron emission tomography scans. Leuk Lymphoma. 2007 Sep;48(9):1721-7. link to original article PubMed

Untreated, pediatric

ABVE-PC

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

Regimen #1, 2 cycles with response adaptation

Study	Evidence
Friedman et al. 2014 (AHOD0031)	Non-randomized portion of RCT

This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by COG P9425; Friedman et al. 2014 does not contain dosing information.

Chemotherapy

Doxorubicin (Adriamycin) 30 mg/m² IV once per day on days 0 & 1
Bleomycin (Blenoxane) 10 IU/m² SC/IV once per day on days 0 & 7
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2.8 mg) IV once per day on days 0 & 7
Etoposide (Vepesid) 75 mg/m² IV once per day on days 0 to 4
Prednisone (Sterapred) 40 mg/m² PO once per day on days 0 to 7
Cyclophosphamide (Cytoxan) 800 mg/m² IV once on day 0

21-day cycle for 2 cycles

Subsequent treatment

Rapid early responders: ABVE-PC x 2 (4 cycles total), then IFRT consolidation x 21 Gy versus no further treatment
Slow early responders: ABVE-PC x 2 (4 cycles total) versus DECA x 2, then ABVE-PC x 2; then IFRT consolidation x 21 Gy

Regimen #2, 3 cycles with response adaptation

Study	Evidence
Schwartz et al. 2009 (COG P9425)	Phase II

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/m² IV once per day on days 0 & 1
Bleomycin (Blenoxane) 10 IU/m² SC/IV once per day on days 0 & 7
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2.8 mg) IV once per day on days 0 & 7
Etoposide (Vepesid) 75 mg/m² IV once per day on days 0 to 4
Prednisone (Sterapred) 40 mg/m² PO once per day on days 0 to 7
Cyclophosphamide (Cytoxan) 800 mg/m² IV once on day 0

Supportive medications

Dexrazoxane (Zinecard) 300 mg/m² IV once per day on days 0, 1, 7 (this was a randomization)
Filgrastim (Neupogen) 5 mcg/kg SC/IV once per day from day 5 until neutrophil recovery (held on day 7)

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 #3, 4 cycles with response adaptation

Study	Evidence
Friedman et al. 2014 (AHOD0031)	Non-randomized portion of RCT

This regimen is intended for pediatric patients, younger than 22 years old. This is the post-amendment dosing described by COG P9425; Friedman et al. 2014 does not contain dosing information.

Preceding treatment

ABVE-PC x 2

Chemotherapy

Doxorubicin (Adriamycin) 30 mg/m² IV once per day on days 0 & 1
Bleomycin (Blenoxane) 10 IU/m² SC/IV once per day on days 0 & 7
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2.8 mg) IV once per day on days 0 & 7
Etoposide (Vepesid) 75 mg/m² IV once per day on days 0 to 4
Prednisone (Sterapred) 40 mg/m² PO once per day on days 0 to 7
Cyclophosphamide (Cytoxan) 800 mg/m² IV once on day 0

21-day cycle for 4 cycles, including the first 2 cycles

Subsequent treatment

Rapid early responders with CR: IFRT consolidation x 21 Gy versus no further treatment
Rapid early responders with less than CR: IFRT consolidation x 21 Gy
Slow early responders: IFRT consolidation x 21 Gy

Regimen #4, 5 cycles

Study	Evidence
Schwartz et al. 2009 (COG P9425)	Phase II

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

Doxorubicin (Adriamycin) 30 mg/m² IV once per day on days 0 & 1
Bleomycin (Blenoxane) 10 IU/m² SC/IV once per day on days 0 & 7
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2.8 mg) IV once per day on days 0 & 7
Etoposide (Vepesid) 75 mg/m² IV once per day on days 0 to 4
Prednisone (Sterapred) 40 mg/m² PO once per day on days 0 to 7
Cyclophosphamide (Cytoxan) 800 mg/m² IV once on day 0

Supportive medications

Dexrazoxane (Zinecard) 300 mg/m² IV once per day on days 0, 1, 7 (this was a randomization)
Filgrastim (Neupogen) 5 mcg/kg SC/IV once per day from day 5 until neutrophil recovery (held on day 7)

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

Subsequent treatment

IFRT consolidation x 21 Gy

References

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 verified protocol link to PMC article PubMed
Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. link to original article does not contain protocol link to PMC article PubMed

OEPA

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OEPA: Oncovin (Vincristine), Etoposide, Prednisone, Adriamycin (Doxorubicin)

Regimen

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

This regimen is meant for boys as it is potentially less gonadotoxic. The original protocol used three doses of dacarbazine per cycle but this was increased to four after a mid-protocol amendment. Patients with early-stage disease only received the OEPA portion, see text for details.

Chemotherapy

Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1, 8, 15
Etoposide (Vepesid) 125 mg/m² IV once per day on days 2 to 6
Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 15
Doxorubicin (Adriamycin) 40 mg/m² IV once per day on days 1 & 15

28-day cycle for 2 cycles

Subsequent treatment

Treatment group 2: COPDAC x 2
Treatment group 3: COPDAC x 4

References

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 verified protocol PubMed

OPPA

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

Regimen

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

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

Chemotherapy

Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1, 8, 15
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 15
Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 15
Doxorubicin (Adriamycin) 40 mg/m² IV once per day on days 1 & 15

28-day cycle for 2 cycles

Subsequent treatment

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

References

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 verified protocol PubMed

Untreated, elderly

BEACOPP

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BEACOPP: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone

Regimen

Study	Evidence	Comparator	Efficacy
Ballova et al. 2005 (GHSG HD9elderly)	Phase III	COPP/ABVD	Seems not superior

Note that this is technically "BEACOPP II." The original "BEACOPP I" is detailed in Diehl et al. 1997 but is of historical interest, only.

Chemotherapy

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 25 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 650 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2mg) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

21-day cycle for 8 cycles

References

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 protocol PubMed

Brentuximab vedotin monotherapy

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Regimen #1, standard-dose

Study	Evidence	Efficacy
Forero-Torres et al. 2015	Phase II	ORR: 92%

Chemotherapy

Brentuximab vedotin (Adcetris) 1.8 mg/kg IV once on day 1

Supportive medications

"according to institutional standards"

21-day cycle for up to 16 cycles, with continuing treatment allowed for those deriving clinical benefit

Regimen #2, reduced-dose

Study	Evidence
Forero-Torres et al. 2015	Phase II, <20 pts in this subgroup

This is the starting dose for severe renal impairment (eGFR less than 30 mL/min/1.73m²) and also the dose reduction for toxicities. While described as a planned starting dose, no patients in the study actually had severe renal impairment.

Chemotherapy

Brentuximab vedotin (Adcetris) 1.2 mg/kg IV once on day 1

Supportive medications

"according to institutional standards"

21-day cycle for up to 16 cycles, with continuing treatment allowed for those deriving clinical benefit

References

Forero-Torres A, Holkova B, Goldschmidt J, Chen R, Olsen G, Boccia RV, Bordoni RE, Friedberg JW, Sharman JP, Palanca-Wessels MC, Wang Y, Yasenchak CA. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood. 2015 Dec 24;126(26):2798-804. Epub 2015 Sep 16. link to original article contains verified protocol link to PMC article PubMed

Brentuximab vedotin & Dacarbazine

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Regimen #1, standard-dose

Study	Evidence	Efficacy
Friedberg et al. 2017	Phase II	ORR: 100%

Chemotherapy

Brentuximab vedotin (Adcetris) 1.8 mg/kg IV once on day 1
Dacarbazine (DTIC) as follows:
- Cycles 1 to 12: 375 mg/m² IV once on day 1
- Cycle 13 onwards: no dacarbazine

21-day cycle for up to 16 cycles, with continuing treatment allowed for those deriving clinical benefit

Regimen #2, reduced-dose

Study	Evidence	Efficacy
Friedberg et al. 2017	Phase II, <20 pts in this subgroup	ORR: 100%

This is the starting dose for severe renal impairment (eGFR less than 30 mL/min/1.73m²). Only 2 patients in the study had severe renal impairment.

Chemotherapy

Brentuximab vedotin (Adcetris) 1.2 mg/kg IV once on day 1
Dacarbazine (DTIC) as follows:
- Cycles 1 to 12: 262 mg/m² IV once on day 1
- Cycle 13 onwards: no dacarbazine

21-day cycle for up to 16 cycles, with continuing treatment allowed for those deriving clinical benefit

References

Friedberg JW, Forero-Torres A, Bordoni RE, Cline VJM, Patel Donnelly D, Flynn PJ, Olsen G, Chen R, Fong A, Wang Y, Yasenchak CA. Frontline brentuximab vedotin in combination with dacarbazine or bendamustine in patients aged ≥60 years with HL. Blood. 2017 Dec 28;130(26):2829-2837. Epub 2017 Oct 16. link to original article contains verified protocol PubMed

ChlVPP

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ChlVPP: Chllorambucil, Vinblastine, Procarbazine, Prednisone

Regimen

Study	Evidence
International ChIVPP Treatment Group 1995	Phase II

Chemotherapy

Chlorambucil (Leukeran) 6 mg/m² (maximum 10 mg/day) PO once per day on days 1 to 14
Vinblastine (Velban) 6 mg/m² (maximum 10 mg/dose) IV once per day on days 1 & 8
Procarbazine (Matulane) 100 mg/m² (maximum 150 mg/day) PO once per day on days 1 to 14
Prednisone (Sterapred) 40 mg PO once per day on days 1 to 14

28-day cycle to complete remission plus 2 cycles; minimum of 6 cycles and maximum of 8 cycles

References

Retrospective: Druker BJ, Rosenthal DS, Canellos GP. Chlorambucil, vinblastine, procarbazine, and prednisone. An effective but less toxic regimen than MOPP for advanced-stage Hodgkin's disease. Cancer. 1989 Mar 15;63(6):1060-4. link to original article PubMed
Selby P, Patel P, Milan S, Meldrum M, Mansi J, Mbidde E, Brada M, Perren T, Forgeson G, Gore M, et al. ChlVPP combination chemotherapy for Hodgkin's disease: long-term results. Br J Cancer. 1990 Aug;62(2):279-85. link to PMC article PubMed
The International ChlVPP Treatment Group. ChlVPP therapy for Hodgkin's disease: experience of 960 patients. Ann Oncol. 1995 Feb;6(2):167-72. link to original article contains protocol PubMed

PVAG

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PVAG: Prednisone, Vinblastine, Adriamycin (Doxorubicin), Gemcitabine

Regimen

Study	Evidence
Böll et al. 2011	Phase II

This regimen was open to patients with early unfavorable disease, but 93% of patients on study had advanced disease.

Chemotherapy

Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5
Vinblastine (Velban) 6 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once on day 1

21-day cycle for 6 to 8 cycles

Patients with PR at the end of treatment underwent 30 Gy of radiotherapy.

References

Böll B, Bredenfeld H, Görgen H, Halbsguth T, Eich HT, Soekler M, Markova J, Keller U, Graeven U, Kremers S, Geissler M, Trenn G, Fuchs M, von Tresckow B, Eichenauer DA, Borchmann P, Engert A. Phase 2 study of PVAG (prednisone, vinblastine, doxorubicin, gemcitabine) in elderly patients with early unfavorable or advanced stage Hodgkin lymphoma. Blood. 2011 Dec 8;118(24):6292-8. Epub 2011 Sep 13. link to original article contains verified protocol PubMed

Consolidation after upfront therapy

COPDAC

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

Regimen #1, 2 cycles

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

Preceding treatment

OEPA x 2

Chemotherapy

Cyclophosphamide (Cytoxan) 500 mg/m² IV once per day on days 1 & 8
Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1 & 8
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 15
Dacarbazine (DTIC) 250 mg/m² IV once per day on days 1 to 4

28-day cycle for 2 cycles

Regimen #2, 4 cycles

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

Preceding treatment

OEPA x 2

Chemotherapy

Cyclophosphamide (Cytoxan) 500 mg/m² IV once per day on days 1 & 8
Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1 & 8
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 15
Dacarbazine (DTIC) 250 mg/m² IV once per day on days 1 to 4

28-day cycle for 4 cycles

References

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 verified protocol PubMed

COPP

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COPP: Cyclophosphamide, Oncovin (Vincristine), Prednisone, Procarbazine

Regimen #1, 2 cycles

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

Preceding treatment

OPPA x 2

Chemotherapy

Cyclophosphamide (Cytoxan) 500 mg/m² IV once per day on days 1 & 8
Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1 & 8
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 15
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 15

28-day cycle for 2 cycles

Regimen #2, 4 cycles

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

Preceding treatment

OPPA x 2

Chemotherapy

Cyclophosphamide (Cytoxan) 500 mg/m² IV once per day on days 1 & 8
Vincristine (Oncovin) 1.5 mg/m² IV once per day on days 1 & 8
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 15
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 15

28-day cycle for 4 cycles

References

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 verified protocol PubMed

Observation

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Regimen

Study	Evidence	Comparator	Efficacy
Borchmann et al. 2011 (GHSG HD12)	Phase III	See link	See link
Radford et al. 2015 (UK NCRI RAPID)	Phase III	IFRT	Inconclusive whether non-inferior

No further treatment.

Preceding treatment

GHSG HD12: Escalated BEACOPP x 8 versus Escalated BEACOPP x 4, then BEACOPP x 4
UK NCRI RAPID: ABVD x 3

References

Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD, Eich HT, Mueller-Hermelink HK, Kanz L, Greil R, Rank A, Paulus U, Smardova L, Huber C, Dörken B, Nerl C, Krause SW, Mueller RP, Fuchs M, Engert A. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011 Nov 10;29(32):4234-42. Epub 2011 Oct 11. link to original article PubMed
Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P, Wimperis J, Culligan D, Popova B, Smith P, McMillan A, Brownell A, Kruger A, Lister A, Hoskin P, O'Doherty M, Barrington S. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015 Apr 23;372(17):1598-607. link to original article contains protocol PubMed

Radiation therapy

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RT: Radiation Therapy

Regimen #1, 20 Gy of involved field RT (IFRT)

Study	Evidence	Comparator	Efficacy
Engert et al. 2010 (GHSG HD10)	Phase III	IFRT x 30 Gy	Seems not superior
Eich et al. 2010 (GHSG HD11)	Phase III	See link	See link

Preceding treatment

GHSG HD10: ABVD x 2 versus ABVD x 4
GHSG HD11: ABVD x 4 versus BEACOPP x 4

Radiotherapy

20 Gy

Regimen #2, 21 Gy of IFRT

Study	Evidence	Comparator	Efficacy
Schwartz et al. 2009 (COG P9425)	Phase II
Friedman et al. 2014 (AHOD0031)	Phase III (C)	Observation	Seems not superior

This regimen is intended for pediatric patients, younger than 22 years old.

Preceding treatment

COG P9425: ABVE-PC x 3 to 5
COG AHOD0031 RERs: ABVE-PC x 4
COG AHOD0031 SERs: ABVE-PC x 4 versus ABVE-PC x 2, DECA x 2, then ABVE-PC x 2

Radiotherapy

21 Gy in 14 fractions of 1.50 Gy per fraction

Regimen #3, 30 Gy of IFRT

Study	Evidence	Comparator	Efficacy
Engert et al. 2010 (GHSG HD10)	Phase III	IFRT x 20 Gy	Seems not superior
Eich et al. 2010 (GHSG HD11)	Phase III	See link	See link
von Tresckow et al. 2012 (GHSG HD14)	Phase III	See link	See link
Advani et al. 2013 (G4)	Non-randomized
Behringer et al. 2014 (GHSG HD13)	Non-randomized portion of RCT
Radford et al. 2015 (UK NCRI RAPID)	Phase III	No further treatment	Inconclusive whether non-inferior

Preceding treatment

GHSG HD10: ABVD x 2 versus ABVD x 4
GHSG HD11: ABVD x 4 versus BEACOPP x 4
GHSG HD14: ABVD x 4 versus ABVD x 2, then Escalated BEACOPP x 2
G4: Stanford V x 8 wk
GHSG HD13: ABVD x 2
UK NCRI RAPID: ABVD x 3

Radiotherapy

30 Gy

Regimen #4, 30 Gy of involved site RT (ISRT)

Study	Evidence	Comparator	Efficacy
Borchmann et al. 2011 (GHSG HD12)	Phase III	See link	See link
Kumar et al. 2016	Phase II

Preceding treatment

GHSG HD12: Escalated BEACOPP x 8 versus Escalated BEACOPP x 4, then BEACOPP x 4
Kumar et al. 2016: BV + AVD x 4

Radiotherapy

30 Gy

Regimen #5, 30 Gy of involved node RT (INRT) + 6 Gy boost

Study	Evidence	Comparator	Efficacy
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10)	Phase III	See link	See link

Preceding treatment

EORTC H10 F: ABVD x 3
EORTC H10 U: ABVD x 4

Radiotherapy

30 Gy (+ 6 Gy boost)

Regimen #6, 30 Gy of extended-field RT (EFRT) + 10 Gy boost

Study	Evidence	Comparator	Efficacy
Engert et al. 2007 (GHSG HD7)	Phase III	EFRT	Superior FFTF

Preceding treatment

GHSG HD7: ABVD x 2

Radiotherapy

30 Gy + 10 Gy to the involved field

Regimen #7, 35 Gy of subtotal nodal irradiation (STNI)

Study	Evidence	Comparator	Efficacy
Meyer et al. 2011 (NCIC CTG/ECOG HD.6)	Phase III	See link	See link

Note: see link for use of STNI as definitive therapy.

Preceding treatment

Unfavorable risk: ABVD x 2

Radiotherapy

35 Gy in 20 fractions

Regimen #8, 36 Gy of IFRT

Study	Evidence	Comparator	Efficacy
Bonadonna et al. 2004	Phase III	STNI x 36 Gy	Seems not superior
Fermé et al. 2007 (EORTC-GELA H8-F)	Phase III	See link	See link
Fermé et al. 2007 (EORTC-GELA H8-U)	Phase III	See link	See link
Advani et al. 2015 (ECOG E2496)	Non-randomized portion of RCT

Preceding treatment

Bonadonna et al. 2004: ABVD x 4, with CR
EORTC-GELA H8-F: MOPP-ABV x 3, with CR
EORTC-GELA H8-U: MOPP-ABV x 4 versus MOPP-ABV x 6, with CR
ECOG E2496: ABVD x 6 to 8 versus Stanford V x 12 wk

Radiotherapy

36 Gy in 18 fractions of 2.00 Gy per fraction

Regimen #9, 36 Gy of STNI

Study	Evidence	Comparator	Efficacy
Bonadonna et al. 2004	Phase III	IFRT x 36 Gy	Seems not superior

Preceding treatment

ABVD x 4, with CR

Radiotherapy

36 Gy to involved sites, 30.6 Gy to uninvolved sites

Regimen #10, 36 Gy of STNI + 4 Gy boost

Study	Evidence	Comparator	Efficacy
Fermé et al. 2007 (EORTC-GELA H8-U)	Phase III	See link	See link

Preceding treatment

MOPP-ABV x 4

Radiotherapy

36 Gy in 18 fractions of 2.00 Gy per fraction, with 4 Gy boost to involved fields

Regimen #11, 40 Gy of IFRT

Study	Evidence	Comparator	Efficacy
Bonadonna et al. 2004	Phase III	STNI x 40 Gy	Seems not superior
Fermé et al. 2007 (EORTC-GELA H8-F)	Phase III	See link	See link
Fermé et al. 2007 (EORTC-GELA H8-U)	Phase III	See link	See link

Preceding treatment

Bonadonna et al. 2004: ABVD x 4, with CRu or PR
EORTC-GELA H8-F: MOPP-ABV x 3, with PR
EORTC-GELA H8-U: MOPP-ABV x 4 versus MOPP-ABV x 6, with PR

Radiotherapy

40 Gy in 20 fractions of 2.00 Gy per fraction

Regimen #12, 40 Gy of STNI

Study	Evidence	Comparator	Efficacy
Bonadonna et al. 2004	Phase III	IFRT x 40 Gy	Seems not superior

Preceding treatment

ABVD x 4, with CRu or PR

Radiotherapy

40 Gy to involved sites, 30.6 Gy to uninvolved sites

References

Carde P, Hagenbeek A, Hayat M, Monconduit M, Thomas J, Burgers MJ, Noordijk EM, Tanguy A, Meerwaldt JH, Le Fur R et al. Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol. 1993 Nov;11(11):2258-72. link to original article PubMed
Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. link to original article PubMed
1. Update: Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. Epub 2012 May 29. link to original article link to PMC article PubMed
Bonadonna G, Bonfante V, Viviani S, Di Russo A, Villani F, Valagussa P. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results. J Clin Oncol. 2004 Jul 15;22(14):2835-41. link to original article contains verified protocol PubMed
Engert A, Franklin J, Eich HT, Brillant C, Sehlen S, Cartoni C, Herrmann R, Pfreundschuh M, Sieber M, Tesch H, Franke A, Koch P, de Wit M, Paulus U, Hasenclever D, Loeffler M, Müller RP, Müller-Hermelink HK, Dühmke E, Diehl V. Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol. 2007 Aug 10;25(23):3495-502. link to original article contains protocol PubMed
1. 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. doi: 10.1200/JCO.2016.70.9410. Epub 2017 Apr 18. link to original article PubMed
Fermé C, Eghbali H, Meerwaldt JH, Rieux C, Bosq J, Berger F, Girinsky T, Brice P, van't Veer MB, Walewski JA, Lederlin P, Tirelli U, Carde P, Van den Neste E, Gyan E, Monconduit M, Diviné M, Raemaekers JM, Salles G, Noordijk EM, Creemers GJ, Gabarre J, Hagenbeek A, Reman O, Blanc M, Thomas J, Vié B, Kluin-Nelemans JC, Viseu F, Baars JW, Poortmans P, Lugtenburg PJ, Carrie C, Jaubert J, Henry-Amar M; EORTC-GELA H8 Trial. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8;357(19):1916-27. link to original article contains verified protocol in supplement PubMed
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 verified protocol link to PMC article PubMed
Engert A, Plütschow A, Eich HT, Lohri A, Dörken B, Borchmann P, Berger B, Greil R, Willborn KC, Wilhelm M, Debus J, Eble MJ, Sökler M, Ho A, Rank A, Ganser A, Trümper L, Bokemeyer C, Kirchner H, Schubert J, Král Z, Fuchs M, Müller-Hermelink HK, Müller RP, Diehl V. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. 2010 Aug 12;363(7):640-52. link to original article PubMed
1. Sub-group analysis: Böll B, Goergen H, Behringer K, Bröckelmann PJ, Hitz F, Kerkhoff A, Greil R, von Tresckow B, Eichenauer DA, Bürkle C, Borchmann S, Fuchs M, Diehl V, Engert A, Borchmann P. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood. 2016 May 5;127(18):2189-92. Epub 2016 Feb 1.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. doi: 10.1200/JCO.2016.70.9410. Epub 2017 Apr 18. link to original article PubMed
Eich HT, Diehl V, Görgen H, Pabst T, Markova J, Debus J, Ho A, Dörken B, Rank A, Grosu AL, Wiegel T, Karstens JH, Greil R, Willich N, Schmidberger H, Döhner H, Borchmann P, Müller-Hermelink HK, Müller RP, Engert A. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010 Sep 20;28(27):4199-206. Epub 2010 Aug 16. link to original article contains verified protocol PubMed
1. 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. doi: 10.1200/JCO.2016.70.9410. Epub 2017 Apr 18. link to original article PubMed
Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD, Eich HT, Mueller-Hermelink HK, Kanz L, Greil R, Rank A, Paulus U, Smardova L, Huber C, Dörken B, Nerl C, Krause SW, Mueller RP, Fuchs M, Engert A. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011 Nov 10;29(32):4234-42. Epub 2011 Oct 11. link to original article PubMed
Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, Horning SJ, Dar AR, Shustik C, Stewart DA, Crump M, Djurfeldt MS, Chen BE, Shepherd LE; NCIC Clinical Trials Group; Eastern Cooperative Oncology Group. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2;366(5):399-408. Epub 2011 Dec 11. link to original article link to PMC article contains verified protocol PubMed
von Tresckow B, Plütschow A, Fuchs M, Klimm B, Markova J, Lohri A, Kral Z, Greil R, Topp MS, Meissner J, Zijlstra JM, Soekler M, Stein H, Eich HT, Mueller RP, Diehl V, Borchmann P, Engert A. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012 Mar 20;30(9):907-13. Epub 2012 Jan 23. link to original article contains verified protocol PubMed
Advani RH, Hoppe RT, Baer D, Mason J, Warnke R, Allen J, Daadi S, Rosenberg SA, Horning SJ. Efficacy of abbreviated Stanford V chemotherapy and involved-field radiotherapy in early-stage Hodgkin lymphoma: mature results of the G4 trial. Ann Oncol. 2013 Apr;24(4):1044-8. Epub 2012 Nov 7. contains limited protocol link to PMC article PubMed
Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed
Friedman DL, Chen L, Wolden S, Buxton A, McCarten K, FitzGerald TJ, Kessel S, De Alarcon PA, Chen AR, Kobrinsky N, Ehrlich P, Hutchison RE, Constine LS, Schwartz CL. Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031. J Clin Oncol. 2014 Nov 10;32(32):3651-8. Epub 2014 Oct 13. link to original article does not contain protocol link to PMC article PubMed
Behringer K, Goergen H, Hitz F, Zijlstra JM, Greil R, Markova J, Sasse S, Fuchs M, Topp MS, Soekler M, Mathas S, Meissner J, Wilhelm M, Koch P, Lindemann HW, Schalk E, Semrau R, Kriz J, Vieler T, Bentz M, Lange E, Mahlberg R, Hassler A, Vogelhuber M, Hahn D, Mezger J, Krause SW, Skoetz N, Böll B, von Tresckow B, Diehl V, Hallek M, Borchmann P, Stein H, Eich H, Engert A; German Hodgkin Study Group; Swiss Group for Clinical Cancer Research; Arbeitsgemeinschaft Medikamentöse Tumortherapie. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin's lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet. 2015 Apr 11;385(9976):1418-27. Epub 2014 Dec 22. Erratum in: Lancet. 2015 Apr 11;385(9976):1396. link to original article PubMed
1. Sub-group analysis: Böll B, Goergen H, Behringer K, Bröckelmann PJ, Hitz F, Kerkhoff A, Greil R, von Tresckow B, Eichenauer DA, Bürkle C, Borchmann S, Fuchs M, Diehl V, Engert A, Borchmann P. Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. Blood. 2016 May 5;127(18):2189-92. Epub 2016 Feb 1.link to original article PubMed
Subgroup analysis: Advani RH, Hong F, Fisher RI, Bartlett NL, Robinson KS, Gascoyne RD, Wagner H Jr, Stiff PJ, Cheson BD, Stewart DA, Gordon LI, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized phase III trial comparing ABVD plus radiotherapy with the Stanford V regimen in patients with stages I or II locally extensive, bulky mediastinal Hodgkin lymphoma: a subset analysis of the North American Intergroup E2496 trial. J Clin Oncol. 2015 Jun 10;33(17):1936-42. Epub 2015 Apr 20. link to original article contains limited protocol link to PMC article PubMed
Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P, Wimperis J, Culligan D, Popova B, Smith P, McMillan A, Brownell A, Kruger A, Lister A, Hoskin P, O'Doherty M, Barrington S. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015 Apr 23;372(17):1598-607. link to original article contains protocol PubMed
Kumar A, Casulo C, Yahalom J, Schöder H, Barr PM, Caron P, Chiu A, Constine LS, Drullinsky P, Friedberg JW, Gerecitano JF, Hamilton A, Hamlin PA, Horwitz SM, Jacob AG, Matasar MJ, McArthur GN, McCall SJ, Moskowitz AJ, Noy A, Palomba ML, Portlock CS, Straus DJ, VanderEls N, Verwys SL, Yang J, Younes A, Zelenetz AD, Zhang Z, Moskowitz CH. Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma. Blood. 2016 Sep 15;128(11):1458-64. Epub 2016 Jul 25. link to original article contains verified protocol link to PMC article PubMed

Relapsed or refractory

ABVD

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

Regimen

Study	Evidence
Radford et al. 2015 (UK NCRI RAPID)	Non-randomized portion of RCT

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.

Preceding treatment

ABVD x 3, with interim PET-CT showing Deauville score 3 to 5 refractory disease

Chemotherapy

Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
Bleomycin (Blenoxane) 10 units/m² IV once per day on days 1 & 15
Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
Dacarbazine (DTIC) 375 mg/m² IV once per day on days 1 & 15

28-day cycle for 1 cycle

Subsequent treatment

IFRT

References

Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P, Wimperis J, Culligan D, Popova B, Smith P, McMillan A, Brownell A, Kruger A, Lister A, Hoskin P, O'Doherty M, Barrington S. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015 Apr 23;372(17):1598-607. link to original article contains protocol PubMed

BEACOPP-14

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BEACOPP-14: Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone, 14-day course

Regimen

Study	Evidence
Johnson et al. 2016 (RATHL)	Non-randomized

Preceding treatment

ABVD x 2, with interim PET-CT showing Deauville score 4 or 5 refractory disease

Chemotherapy

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 25 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 650 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2mg) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisolone (Millipred) 80 mg/m² PO once per day on days 1 to 7

Supportive medications

G-CSF 263/300 μg SC once per day on days 9 to 13 OR
Pegfilgrastim (Neulasta) (dose/day not specified) SC once

14-day cycle for 4 to 6 cycles

References

Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A, d'Amore F, Enblad G, Franceschetto A, Fulham M, Luminari S, O'Doherty M, Patrick P, Roberts T, Sidra G, Stevens L, Smith P, Trotman J, Viney Z, Radford J, Barrington S. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. N Engl J Med. 2016 Jun 23;374(25):2419-29. link to original article link to protocol contains verified protocol in supplement link to PMC article PubMed

BeGEV

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BeGEV: Bendamustine, GEmcitabine, Vinorelbine

Regimen

Study	Evidence
Santoro et al. 2016	Phase II

Chemotherapy

Bendamustine 90 mg/m² IV once per day on days 2 & 3
Gemcitabine (Gemzar) 800 mg/m² IV once per day on days 1 & 4
Vinorelbine (Navelbine) 20 mg/m² IV once on day 1
Prednisolone (Millipred) 100 mg PO once per day on days 1 to 4

Supportive medications

Growth factor support
PJP prophylaxis and antiemetics in accordance with institutional guidelines

21-day cycle for 4 cycles

Patients in who achieved a CR or PR proceeded to BEAM, then autologous hematopoietic cell transplant or FEAM, then autologous hematopoietic cell transplant.

References

Santoro A, Mazza R, Pulsoni A, Re A, Bonfichi M, Zilioli VR, Salvi F, Merli F, Anastasia A, Luminari S, Annechini G, Gotti M, Peli A, Liberati AM, Di Renzo N, Castagna L, Giordano L, Carlo-Stella C. Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study. J Clin Oncol. 2016 Sep 20;34(27):3293-9. Epub 2016 Jul 5. link to original article contains verified protocol PubMed

Bendamustine monotherapy

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Regimen

Study	Evidence	Efficacy
Moskowitz et al. 2013	Phase II	ORR: 53%

Chemotherapy

Note: these infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.

Bendamustine 120 mg/m² IV over 30 minutes once per day on days 1 & 2

Supportive medications

Filgrastim (Neupogen) or Pegfilgrastim (Neulasta) used each cycle; paper does not specify exact timing/duration
PCP prophylaxis and antiemetics according to institutional guidelines

28-day cycle for up to 6 cycles

References

Moskowitz AJ, Hamlin PA Jr, Perales MA, Gerecitano J, Horwitz SM, Matasar MJ, Noy A, Palomba ML, Portlock CS, Straus DJ, Graustein T, Zelenetz AD, Moskowitz CH. Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. J Clin Oncol. 2013 Feb 1;31(4):456-60. Epub 2012 Dec 17. link to original article contains verified protocol link to PMC article PubMed

Bendamustine & Brentuximab vedotin

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Regimen

Study	Evidence
LaCasce et al. 2014	Phase II

Chemotherapy

Bendamustine 90 mg/m² IV once per day on days 1 & 2
Brentuximab vedotin (Adcetris) 1.8 mg/kg IV once on day 1

21-day cycle for up to 6 cycles

References

Abstract: LaCasce A, Bociek RG, Matous J, et al. Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory after Frontline Therapy. Presented at: 2014 ASH Annual Meeting; December 6-9, 2014; San Francisco, CA. Abstract 293 link to abstract.

Brentuximab vedotin monotherapy

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Regimen #1

Study	Evidence
Younes et al. 2012 (SG035-0003)	Phase II
Gopal et al. 2012	Non-randomized
Bartlett et al. 2014	Phase II

Note: Bartlett et al. 2014 is a re-treatment trial; all patients were previously exposed to brentuximab vedotin. Patients who had received the 1.2 mg/kg dose on a prior trial also received that dose at re-treatment.

Chemotherapy

Brentuximab vedotin (Adcetris) 1.8 mg/kg IV over 30 minutes once on day 1

Supportive medications

Rothe et al. 2012: "no premedications were administered"

21-day cycles, given until progression or up to 16 infusions (SG035-0003)

Regimen #2

Study	Evidence
Moskowitz et al. 2015	Phase II

Chemotherapy

Brentuximab vedotin (Adcetris) 1.2 mg/kg IV once per day on days 1, 8, 15

28-day cycle for 2 cycles

PET-negative patients (a Deauville score of 1 or 2) proceeded to autologous hematopoietic cell transplant with BEAM, CBV, or high dose chemoradiotherapy. All others proceeded to receive two cycles of augmented ICE prior to transplant.

References

Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012 Jun 20;30(18):2183-9. Epub 2012 Mar 26. link to original article contains verified protocol link to PMC article PubMed
1. Update: Gopal AK, Chen R, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Connors JM, Engert A, Larsen EK, Chi X, Sievers EL, Younes A. Durable remissions in a pivotal phase 2 study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2015 Feb 19;125(8):1236-43. Epub 2014 Dec 22. link to original article link to PMC article PubMed
2. Update: Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Connors JM, Engert A, Larsen EK, Huebner D, Fong A, Younes A. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2016 Sep 22;128(12):1562-6. Epub 2016 Jul 18. link to original article link to PMC article PubMed
Gopal AK, Ramchandren R, O'Connor OA, Berryman RB, Advani RH, Chen R, Smith SE, Cooper M, Rothe A, Matous JV, Grove LE, Zain J. Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood. 2012 Jul 19;120(3):560-8. Epub 2012 Apr 17. link to original article contains verified protocol link to PMC article PubMed
Retrospective: Rothe A, Sasse S, Goergen H, Eichenauer DA, Lohri A, Jäger U, Bangard C, Böll B, von Bergwelt Baildon M, Theurich S, Borchmann P, Engert A. Brentuximab vedotin for relapsed or refractory CD30+ hematologic malignancies: the German Hodgkin Study Group experience. Blood. 2012 Aug 16;120(7):1470-2. Epub 2012 Jul 11. link to original article contains verified protocol PubMed
Gibb A, Jones C, Bloor A, Kulkarni S, Illidge T, Linton K, Radford J. Brentuximab vedotin in refractory CD30+ lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center. Haematologica. 2013 Apr;98(4):611-4. Epub 2012 Oct 12. link to original article contains verified protocol link to PMC article PubMed
Retrospective: Gopal AK, Bartlett NL, Forero-Torres A, Younes A, Chen R, Friedberg JW, Matous JV, Shustov AR, Smith SE, Zain J, O'Meara MM, Fanale MA. Brentuximab vedotin in patients aged 60 years or older with relapsed or refractory CD30-positive lymphomas: a retrospective evaluation of safety and efficacy. Leuk Lymphoma. 2014 Oct;55(10):2328-34. Epub 2014 Feb 24. link to original article PubMed
Bartlett NL, Chen R, Fanale MA, Brice P, Gopal A, Smith SE, Advani R, Matous JV, Ramchandren R, Rosenblatt JD, Huebner D, Levine P, Grove L, Forero-Torres A. Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies. J Hematol Oncol. 2014 Mar 19;7:24. link to original article contains verified protocol link to PMC article PubMed
Moskowitz AJ, Schöder H, Yahalom J, McCall SJ, Fox SY, Gerecitano J, Grewal R, Hamlin PA, Horwitz S, Kobos R, Kumar A, Matasar M, Noy A, Palomba ML, Perales MA, Portlock CS, Sauter C, Shukla N, Steinherz P, Straus D, Trippett T, Younes A, Zelenetz A, Moskowitz CH. PET-adapted sequential salvage therapy with brentuximab vedotin followed by augmented ifosamide, carboplatin, and etoposide for patients with relapsed and refractory Hodgkin's lymphoma: a non-randomised, open-label, single-centre, phase 2 study. Lancet Oncol. 2015 Mar;16(3):284-92. Epub 2015 Feb 13. link to original article contains protocol PubMed
Chen R, Palmer JM, Martin P, Tsai N, Kim Y, Chen BT, Popplewell L, Siddiqi T, Thomas SH, Mott M, Sahebi F, Armenian S, Leonard J, Nademanee A, Forman SJ. Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin Lymphoma. Biol Blood Marrow Transplant. 2015 Dec;21(12):2136-40. Epub 2015 Jul 26. link to original article link to PMC article PubMed

DHAP

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DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study	Evidence
Valesquez et al. 1988	Phase II
Sureda et al. 2011	Phase II

Chemotherapy

Dexamethasone (Decadron) 40 mg PO/IV over 15 minutes once per day on days 1 to 4
Cytarabine (Cytosar) as follows:
- 70 and younger: 2000 mg/m² IV given over 3 hours Q12H x 2 doses on day 2
- >70 years old: 1000 mg/m² IV given over 3 hours Q12H x 2 doses on day 2
Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours on day 1

Supportive medications

Normal saline with mannitol 50 g/L given at 250 mL/H x 36 hours, starting 6 hours before Cisplatin (Platinol) infusion was started

21 to 28-day cycles (depending on degree of myelosuppression)

Velasquez et al. 1988 gave 6 to 10 cycles, with therapy given 4 cycles beyond the maximum antitumor effect. Sureda et al. 2011 gave 2 cycles, with responders proceeding to RIC allogeneic hematopoietic cell transplant.

Aside from the table below (from Velasquez et al. 1988), there were no specific cutoff criteria about dose modifications or delays of treatment.

Dose modifications
Event	Cytarabine (Cytosar)	Cisplatin (Platinol)
ANC less than 200/uL	1000 mg/m² x 2 doses	100 mg/m²
Platelets less than 20 x 10⁹/L	1000 mg/m² x 2 doses	100 mg/m²
Sepsis associated with neutropenia	500 mg/m² x 1 dose	100 mg/m²
Cr 1.5 to 2.0	-	75 mg/m²
Cr 2.1-3.0	-	50 mg/m²

References

Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, Barlogie B. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. link to original article contains protocol PubMed
Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M, Passweg J, Martino R, Valcárcel D, Besalduch J, Duarte R, León A, Pascual MJ, García-Noblejas A, López Corral L, Xicoy B, Sierra J, Schmitz N. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin's lymphoma. Results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2012 Feb;97(2):310-7. Epub 2011 Oct 11. link to original article contains protocol link to PMC article PubMed

DHAP - time intensified

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DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study	Evidence
Josting et al. 2002	Phase II

This was used as a salvage regimen for relapsed/refractory Hodgkin Lymphoma in patients who were planned for high-dose chemotherapy (HDCT) and autologous hematopoietic cell transplantation.

Chemotherapy

Dexamethasone (Decadron) 40 mg IV once per day on days 1 to 4
Cytarabine (Cytosar) 2000 mg/m² IV given over 3 hours Q12H x 2 doses on day 2
Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours on day 1

Supportive medications

Hydration at 250 mL/H started 2 to 6 hours before Cisplatin (Platinol) infusion was started
Prednisolone acetate 1% eyedrops 1 drop to both eyes TID; start 12 hours before start of Cytarabine (Cytosar) and continued for 2 days after cytarabine administration complete
Ondansetron (Zofran) 8 mg IV once per day on days 1 & 2
Filgrastim (Neupogen) 5 mcg/kg SQ per day, start 24 hours after last dose of Cytarabine (Cytosar) and continue until ANC greater than 2500/uL for 3 days

Variable number of days between cycles depending on count recovery x 2 cycles Median time between cycle 1 and 2 was 16 days. The paper did not definitively specify what criteria needed to be fulfilled before cycle 2 was given. Baseline eligibility criteria for the study included WBC count greater than 3.5 x 10⁹/L, Hb greater than or equal to 8 g/dL, platelets greater than or equal to 100 x 10⁹/L.

References

Josting A, Rudolph C, Reiser M, Mapara M, Sieber M, Kirchner HH, Dörken B, Hossfeld DK, Diehl V, Engert A; Participating Centers. Time-intensified dexamethasone/cisplatin/cytarabine: an effective salvage therapy with low toxicity in patients with relapsed and refractory Hodgkin's disease. Ann Oncol. 2002 Oct;13(10):1628-35. link to original article contains protocol PubMed

Escalated BEACOPP

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eBEACOPP: escalated Bleomycin, Etoposide, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone

Regimen #1, 2 cycles

Study	Evidence
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10)	Non-randomized portion of RCT

Note: dosing is not described in the paper; this is the standard escalated BEACOPP as described elsewhere.

Preceding treatment

EORTC H10 F: ABVD x 2, with interim PET-CT showing Deauville score 3 to 5 refractory disease
EORTC H10 U: ABVD x 2, with interim PET-CT showing Deauville score 3 to 5 refractory disease

Chemotherapy

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 200 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1200 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2mg per cycle) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

21-day cycle for 2 cycles

Subsequent treatment

INRT

Regimen #2, 3 cycles with response adaptation

Study	Evidence
Johnson et al. 2016 (RATHL)	Non-randomized

Preceding treatment

ABVD x 2, with interim PET-CT showing Deauville score 4 or 5 refractory disease

Chemotherapy

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 200 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1250 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2mg per cycle) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisolone (Millipred) 40 mg/m² PO once per day on days 1 to 14

Supportive medications

G-CSF 263/300 μg SC once per day on days 9 to 13 OR
Pegfilgrastim (Neulasta) (dose/day not specified) SC once

21-day cycle for 3 cycles

Subsequent treatment

Second interim PET-CT negative: eBEACOPP x 1 (4 total)

Regimen #3, 4 cycles

Study	Evidence
Borchmann et al. 2017 (GHSG HD18)	Non-randomized portion of RCT

Note: patients in GHSG HD18 enrolled after June 2011 would receive a total of 6 cycles.

Preceding treatment

eBEACOPP x 2, with positive interim PET-CT

Chemotherapy

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 200 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1200 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2mg per cycle) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

21-day cycle for 4 cycles

Regimen #4, 6 cycles

Study	Evidence	Comparator	Efficacy
Press et al. 2016 (SWOG S0816)	Phase II
Borchmann et al. 2017 (GHSG HD18)	Phase III	R-BEACOPP_escalated	Seems not superior

Note: patients in GHSG HD18 enrolled prior to June 2011 would receive a total of 8 cycles.

Preceding treatment

SWOG S0816: ABVD x 2, with interim PET-CT showing Deauville score 4 or 5 refractory disease
GHSG HD18: eBEACOPP x 2, with positive interim PET-CT

Chemotherapy

Bleomycin (Blenoxane) 10 units/m² IV once on day 8
Etoposide (Vepesid) 200 mg/m² IV once per day on days 1 to 3
Doxorubicin (Adriamycin) 35 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 1200 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2mg per cycle) IV once on day 8
Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 7
Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

21-day cycle for 6 cycles

References

Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed
Press OW, Li H, Schöder H, Straus DJ, Moskowitz CH, LeBlanc M, Rimsza LM, Bartlett NL, Evens AM, Mittra ES, LaCasce AS, Sweetenham JW, Barr PM, Fanale MA, Knopp MV, Noy A, Hsi ED, Cook JR, Lechowicz MJ, Gascoyne RD, Leonard JP, Kahl BS, Cheson BD, Fisher RI, Friedberg JW. US Intergroup trial of response-adapted therapy for stage III to IV Hodgkin lymphoma using early interim fluorodeoxyglucose-positron emission tomography imaging: Southwest Oncology Group S0816. J Clin Oncol. 2016 Jun 10;34(17):2020-7. Epub 2016 Apr 11. link to original article refers to original protocol link to PMC article PubMed
Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A, d'Amore F, Enblad G, Franceschetto A, Fulham M, Luminari S, O'Doherty M, Patrick P, Roberts T, Sidra G, Stevens L, Smith P, Trotman J, Viney Z, Radford J, Barrington S. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin's lymphoma. N Engl J Med. 2016 Jun 23;374(25):2419-29. link to original article link to protocol contains verified protocol in supplement link to PMC article PubMed
Borchmann P, Haverkamp H, Lohri A, Mey U, Kreissl S, Greil R, Markova J, Feuring-Buske M, Meissner J, Dührsen U, Ostermann H, Keller U, Maschmeyer G, Kuhnert G, Dietlein M, Kobe C, Eich H, Baues C, Stein H, Fuchs M, Diehl V, Engert A. Progression-free survival of early interim PET-positive patients with advanced stage Hodgkin's lymphoma treated with BEACOPP(escalated) alone or in combination with rituximab (HD18): an open-label, international, randomised phase 3 study by the German Hodgkin Study Group. Lancet Oncol. 2017 Apr;18(4):454-463. Epub 2017 Feb 22. link to original article PubMed
1. Update: Borchmann P, Goergen H, Kobe C, Lohri A, Greil R, Eichenauer DA, Zijlstra JM, Markova J, Meissner J, Feuring-Buske M, Hüttmann A, Dierlamm J, Soekler M, Beck HJ, Willenbacher W, Ludwig WD, Pabst T, Topp MS, Hitz F, Bentz M, Keller UB, Kühnhardt D, Ostermann H, Schmitz N, Hertenstein B, Aulitzky W, Maschmeyer G, Vieler T, Eich H, Baues C, Stein H, Fuchs M, Kuhnert G, Diehl V, Dietlein M, Engert A. PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group. Lancet. 2017 Oct 20. [Epub ahead of print] link to original article PubMed

ESHAP

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ESHAP: Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study	Evidence
Aparicio et al. 1999	Phase II

Note that the authors state that they used the protocol defined by Velasquez et al. 1994. However, there are some differences in the text describing methylprednisolone dosing from that in the original article. Below are the doses reported in the original article, with the addition of G-CSF as specified in Aparicio et al. 1999.

Chemotherapy

Etoposide (Vepesid) 40 mg/m² IV over 60 minutes once per day on days 1 to 4
Methylprednisolone (Solumedrol) 250 to 500 mg IV over 15 minutes once per day on days 1 to 5
Cytarabine (Cytosar) 2000 mg/m² IV over 2 hours once on day 5
Cisplatin (Platinol) 25 mg/m²/day IV continuous infusion on days 1 to 4 (total dose per cycle: 100 mg/m²)

Supportive medications

At least 1 liter normal saline with 25 to 50 g Mannitol once per day throughout chemotherapy
Metoclopramide (Reglan) 0.5 to 1 mg/kg "given regularly"
Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 6 to 18

21- to 28-day cycle for 3 cycles; see below

Transplant eligible patients with "responsive disease" after 3 cycles proceeded to receive CBV followed by autologous transplant. Transplant ineligible patients with "responsive disease" received 3 more cycles of ESHAP (6 total).

References

Aparicio J, Segura A, Garcerá S, Oltra A, Santaballa A, Yuste A, Pastor M. ESHAP is an active regimen for relapsing Hodgkin's disease. Ann Oncol. 1999 May;10(5):593-5. link to original article contains verified protocol PubMed

Everolimus monotherapy

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Regimen

Study	Evidence
Johnston et al. 2010	Phase II

Chemotherapy

Everolimus (Afinitor) 10 mg PO once per day on an empty stomach

Supportive medications

"Patients could receive white blood cell growth factors if neutropenia developed. Erythropoietin treatment for anemia was permitted."

28-day cycles, given until progression or unacceptable toxicity

References

Johnston PB, Inwards DJ, Colgan JP, Laplant BR, Kabat BF, Habermann TM, Micallef IN, Porrata LF, Ansell SM, Reeder CB, Roy V, Witzig TE. A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma. Am J Hematol. 2010 May;85(5):320-4. link to original article contains verified protocol link to PMC article PubMed

GCD

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GCD: Gemcitabine, Carboplatin, Dexamethasone

Regimen

Study	Evidence
Gopal et al. 2010	Phase II

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1 & 8
Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4

Supportive medications

Growth factor support and antibiotic prophylaxis used is at the discretion of the treating physician.

21-day cycle for up to 4 cycles

Dose modifications

Gemcitabine (Gemzar):
- If on day 8, platelets are 50 to 100 x 10⁹/L or ANC 500 to 1000/uL: reduce dose by 25% for that dose only.
- If on day 8, platelets are less than 50 x 10⁹/L or ANC less than 500/uL: No day 8 dose given.
- Subsequent cycles would be given at full dose if patients had platelets greater than or equal to 50 x 10⁹/L or ANC greater than or equal to 1000/uL.
- If counts were not adequate, the next cycle can be delayed for up to 3 weeks until counts are adequate for treatment.

References

Gopal AK, Press OW, Shustov AR, Petersdorf SH, Gooley TA, Daniels JT, Garrison MA, Gjerset GF, Lonergan M, Murphy AE, Smith JC, Pagel JM. Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. Leuk Lymphoma. 2010 Aug;51(8):1523-9. contains verified protocol link to PMC article PubMed

GCD-R

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GCD-R: Gemcitabine, Carboplatin, Dexamethasone, Rituximab

Regimen

Study	Evidence
Gopal et al. 2010	Phase II

Only used when disease is CD20+.

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1 & 8
Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1
Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
Rituximab (Rituxan) 375 mg/m² slow IV infusion once on day 8

Supportive medications

Growth factor support and antibiotic prophylaxis used is at the discretion of the treating physician.

21-day cycle for up to 4 cycles

Dose modifications

Gemcitabine (Gemzar):
- If on day 8, platelets are 50 to 100 x 10⁹/L or ANC 500 to 1000/uL: reduce dose by 25% for that dose only.
- If on day 8, platelets are less than 50 x 10⁹/L or ANC less than 500/uL: No day 8 dose given.
- Subsequent cycles would be given at full dose if patients had platelets greater than or equal to 50 x 10⁹/L or ANC greater than or equal to 1000/uL.
- If counts were not adequate, the next cycle can be delayed for up to 3 weeks until counts are adequate for treatment.

References

Gopal AK, Press OW, Shustov AR, Petersdorf SH, Gooley TA, Daniels JT, Garrison MA, Gjerset GF, Lonergan M, Murphy AE, Smith JC, Pagel JM. Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium. Leuk Lymphoma. 2010 Aug;51(8):1523-9. contains verified protocol link to PMC article PubMed

Gemcitabine monotherapy

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Regimen

Study	Evidence
Santoro et al. 2000	Phase II

Chemotherapy

Gemcitabine (Gemzar) as follows:
- Cycle 1: 1250 mg/m² IV over 30 minutes once per day on days 1, 8, 15
- Subsequent cycles (if no hematologic or nonhematologic toxicities): 1500 mg/m² IV over 30 minutes once per day on days 1, 8, 15

28-day cycles until progression or intolerance

References

Santoro A, Bredenfeld H, Devizzi L, Tesch H, Bonfante V, Viviani S, Fiedler F, Parra HS, Benoehr C, Pacini M, Bonadonna G, Diehl V. Gemcitabine in the treatment of refractory Hodgkin's disease: results of a multicenter phase II study. J Clin Oncol. 2000 Jul;18(13):2615-9. link to original article contains verified protocol PubMed

Gemcitabine & Rituximab

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Regimen

Study	Evidence
Oki et al. 2007	Phase II

Patients had received at least 2 prior chemotherapy regimens.

Chemotherapy

Gemcitabine (Gemzar) 1250 mg/m² IV over 30 minutes once per day on days 1 & 8
Rituximab (Rituxan) 375 mg/m² IV once per week for the first 2 cycles (6 doses total)

21-day cycle for up to 6 cycles

Dose modifications

Gemcitabine (Gemzar):
- Dose level 0: 1250 mg/m²
- Dose level -1: 1000 mg/m²
- Dose level -2: 750 mg/m²
- If ANC less than or equal to 1000/uL on day 1 of the following cycle, delay until count recovery
- If ANC remains less than or equal to 1000/uL for one week or longer, reduce dose by one level
- If platelets less than or equal to 50 x 10⁹/L on day 1 of the following cycle, delay until count recovery AND reduce dose by one level

References

Oki Y, Pro B, Fayad LE, Romaguera J, Samaniego F, Hagemeister F, Neelapu S, McLaughlin P, Goy A, Younes A. Phase 2 study of gemcitabine in combination with rituximab in patients with recurrent or refractory Hodgkin lymphoma. Cancer. 2008 Feb 15;112(4):831-6. link to original article contains verified protocol PubMed

GVD

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GVD: Gemcitabine, Vinorelbine, Doxil (Liposomal doxorubicin)

Regimen

Study	Evidence
Bartlett et al. 2007 (CALGB 59804)	Phase II

Transplant-naive patients

Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1 & 8 second medication given
Vinorelbine (Navelbine) 20 mg/m² IV over 6 to 10 minutes once per day on days 1 & 8 first medication given
Pegylated liposomal doxorubicin (Doxil) 15 mg/m² IV over 30 to 60 minutes once per day on days 1 & 8 third medication given

21-day cycle for 2 to 6 cycles

Post-transplant patients

Gemcitabine (Gemzar) 800 mg/m² IV over 30 minutes once per day on days 1 & 8 second medication given
Vinorelbine (Navelbine) 15 mg/m² IV over 6 to 10 minutes once per day on days 1 & 8 first medication given
Pegylated liposomal doxorubicin (Doxil) 10 mg/m² IV over 30 to 60 minutes once per day on days 1 & 8 third medication given

21-day cycle for 2 to 6 cycles

Dose levels: Note: These dose levels are listed primarily for historical purposes and were used in the trial while dose levels and dose limiting toxicities (DLT) and maximum tolerated dose (MTD) were being determined. The MTD dosages used above correspond to dose level 1 for transplant-naive patients and dose level -1 for post-transplant patients.

Dose level 1:
- Vinorelbine (Navelbine) 20 mg/m² IV over 6 to 10 minutes once per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1 & 8
- Pegylated liposomal doxorubicin (Doxil) 15 mg/m² IV over 30 to 60 minutes once per day on days 1 & 8
Dose level 2:
- Vinorelbine (Navelbine) 20 mg/m² IV over 6 to 10 minutes once per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m² IV over 30 minutes once per day on days 1 & 8
- Pegylated liposomal doxorubicin (Doxil) 20 mg/m² IV over 30 to 60 minutes once per day on days 1 & 8
Dose level -1:
- Vinorelbine (Navelbine) 15 mg/m² IV over 6 to 10 minutes once per day on days 1 & 8
- Gemcitabine (Gemzar) 800 mg/m² IV over 30 minutes once per day on days 1 & 8
- Pegylated liposomal doxorubicin (Doxil) 10 mg/m² IV over 30 to 60 minutes once per day on days 1 & 8

Dose modifications

If febrile neutropenia occurs: Decrease treatment by one dose level.
If febrile neutropenia occurs on dose level -1: treating physician can choose to either:
1. Use Filgrastim (Neupogen) or Sargramostim (Leukine).
2. Reduce dose of Gemcitabine (Gemzar) and Vinorelbine (Navelbine) by 25% for all subsequent cycles.
If febrile neutropenia reoccurred despite dose reduction patient were discontinued from this protocol.

Gemcitabine (Gemzar):
- If on day 8, platelets are 50 to 100 x 10⁹/L or ANC 500 to 1000/uL: reduce dose by 25% for that dose only.
- If on day 8, platelets are less than 50 x 10⁹/L or ANC less than 500/uL: No day 8 dose given.
- Subsequent cycles would be given at full dose if patients had platelets greater than or equal to 50 x 10⁹/L or ANC greater than or equal to 1000/uL.
- If counts were not adequate, the next cycle can be delayed for up to 3 weeks until counts are adequate for treatment.

References

Bartlett NL, Niedzwiecki D, Johnson JL, Friedberg JW, Johnson KB, van Besien K, Zelenetz AD, Cheson BD, Canellos GP; Cancer Leukemia Group B. Gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD), a salvage regimen in relapsed Hodgkin's lymphoma: CALGB 59804. Ann Oncol. 2007 Jun;18(6):1071-9. link to original article contains protocol PubMed

GVP

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GVP: Gemcitabine, Vinorelbine, Prednisolone

Regimen

Study	Evidence
Naqi et al. 2013	Phase II

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8
Vinorelbine (Navelbine) 30 mg/m² IV over 6 to 10 minutes once per day on days 1 & 8
Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5

28-day cycle for 4 cycles

References

Naqi N, Ahmad S, Shah I, Khattak J. A multicentre phase-II feasibility study evaluating gemcitabine/vinorelbine / prednisolone combination chemotherapy in relapsed / refractory Hodgkin's lymphoma. J Coll Physicians Surg Pak. 2013 Jun;23(6):397-400. PubMed

ICE

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ICE: Ifosfamide, Carboplatin, Etoposide

Regimen #1

Study	Evidence
Moskowitz et al. 2001	Phase II

Chemotherapy

Ifosfamide (Ifex) 5000 mg/m² IV continuous infusion over 24 hours on day 2; mixed in same solution as Mesna (Mesnex)
Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV once on day 2
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3

Supportive medications

Mesna (Mesnex) 5000 mg/m² IV continuous infusion over 24 hours on day 2; mixed in same solution as Ifosfamide (Ifex)
Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 5 to 12
No dose reductions--treatment is delayed until ANC is greater than 1000/uL and platelets greater than 50 x 10⁹/L

14-day cycle for 2 cycles

Regimen #2, "Augmented ICE"

Study	Evidence
Moskowitz et al. 2015	Phase II

Preceding treatment

Brentuximab vedotin

Chemotherapy

Ifosfamide (Ifex) 5000 mg/m²/day IV continuous infusion over 48 hours on days 1 & 2 (total dose per cycle: 10,000 mg/m²); mixed in same solution as Mesna (Mesnex)
Carboplatin (Paraplatin) AUC 5 IV once on day 3
Etoposide (Vepesid) 200 mg/m² IV q12h on day 1 (3 doses total)

Supportive medications

Mesna (Mesnex) 5000 mg/m²/day IV continuous infusion over 48 hours on days 1 & 2; mixed in same solution as Ifosfamide (Ifex)

2 cycles

Autologous hematopoietic cell transplant was "considered" after 2 cycles; criteria not listed in the abstract.

References

Moskowitz CH, Nimer SD, Zelenetz AD, Trippett T, Hedrick EE, Filippa DA, Louie D, Gonzales M, Walits J, Coady-Lyons N, Qin J, Frank R, Bertino JR, Goy A, Noy A, O'Brien JP, Straus D, Portlock CS, Yahalom J. A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood. 2001 Feb 1;97(3):616-23. link to original article contains protocol PubMed
Moskowitz AJ, Schöder H, Yahalom J, McCall SJ, Fox SY, Gerecitano J, Grewal R, Hamlin PA, Horwitz S, Kobos R, Kumar A, Matasar M, Noy A, Palomba ML, Perales MA, Portlock CS, Sauter C, Shukla N, Steinherz P, Straus D, Trippett T, Younes A, Zelenetz A, Moskowitz CH. PET-adapted sequential salvage therapy with brentuximab vedotin followed by augmented ifosamide, carboplatin, and etoposide for patients with relapsed and refractory Hodgkin's lymphoma: a non-randomised, open-label, single-centre, phase 2 study. Lancet Oncol. 2015 Mar;16(3):284-92. Epub 2015 Feb 13. link to original article contains protocol PubMed

Ifosfamide & Vinorelbine

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Regimen

Study	Evidence
Bonfante et al. 1998	Phase II

Chemotherapy

Ifosfamide (Ifex) 3000 mg/m²/day IV continuous infusion on days 1 to 4 (total dose per cycle: 12,000 mg/m²)
Vinorelbine (Navelbine) 25 mg/m² IV once per day on days 1 & 5

Supportive medications

Mesna (Mesnex) 3000 mg/m²/day IV admixed with Ifosfamide (Ifex)
Prednisone (Sterapred) 50 mg IV once per day on days 1 to 5
Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 7 to 14

21-day cycles

References

Bonfante V, Viviani S, Santoro A, Devizzi L, Di Russo A, Zanini M, Soncini F, Soto Parra H, Valagussa P, Bonadonna G. Ifosfamide and vinorelbine: an active regimen for patients with relapsed or refractory Hodgkin's disease. Br J Haematol. 1998 Nov;103(2):533-5. link to original article contains verified protocol PubMed
Bonfante V, Viviani S, Devizzi L, Di Russo A, Di Nicola M, Magni M, Matteucci P, Grisanti S, Valagussa P, Bonadonna G, Gianni AM. High-dose ifosfamide and vinorelbine as salvage therapy for relapsed or refractory Hodgkin's disease. Eur J Haematol Suppl. 2001 Jul;64:51-5. contains protocol PubMed

IGEV

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IGEV: Ifosfamide, GEmcitabine, Vinorelbine

Regimen

Study	Evidence
Santoro et al. 2007	Phase II
Zinzani et al. 2016 (HD0801)	Non-randomized

Preceding treatment

HD0801: ABVD x 2

Chemotherapy

Ifosfamide (Ifex) 2000 mg/m² IV over 2 hours once per day on days 1 to 4
Gemcitabine (Gemzar) 800 mg/m² IV once per day on days 1 & 4
Vinorelbine (Navelbine) 20 mg/m² IV once on day 1
Prednisolone (Millipred) 100 mg PO once per day on days 1 to 4

Supportive medications

2L saline solution hyperhydration days 1 to 4
Mesna (Mesnex) 2600 mg/m² IV once per day on days 1 to 4
Filgrastim (Neupogen) (dose not specified, but could assume 5 mcg/kg) SC once per day on days 7 to 12, or up to apheresis in the course of hematopoietic cell mobilization

21-day cycle for 4 cycles

Patients in HD0801 who achieved a CR proceeded to BEAM, then autologous hematopoietic cell transplant.

References

Santoro A, Magagnoli M, Spina M, Pinotti G, Siracusano L, Michieli M, Nozza A, Sarina B, Morenghi E, Castagna L, Tirelli U, Balzarotti M. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma. Haematologica. 2007 Jan;92(1):35-41. link to original article contains verified protocol PubMed
Zinzani PL, Broccoli A, Gioia DM, Castagnoli A, Ciccone G, Evangelista A, Santoro A, Ricardi U, Bonfichi M, Brusamolino E, Rossi G, Anastasia A, Zaja F, Vitolo U, Pavone V, Pulsoni A, Rigacci L, Gaidano G, Stelitano C, Salvi F, Rusconi C, Tani M, Freilone R, Pregno P, Borsatti E, Sacchetti GM, Argnani L, Levis A. Interim positron emission tomography response-adapted therapy in advanced-stage Hodgkin lymphoma: final results of the phase II part of the HD0801 study. J Clin Oncol. 2016 Apr 20;34(12):1376-85. Epub 2016 Feb 16. link to original article refers to Santoro et al. 2007 PubMed

Lenalidomide monotherapy

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Regimen

Study	Evidence
Fehniger et al. 2011	Phase II

Chemotherapy

Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

Supportive medications

Aspirin (81 or 325 mg) PO once per day as prophylactic anticoagulation; those "deemed to be at high risk of deep venous thrombosis by the treating physician" were given Warfarin (Coumadin) or low-molecular-weight heparin.

28-day cycles

References

Fehniger TA, Larson S, Trinkaus K, Siegel MJ, Cashen AF, Blum KA, Fenske TS, Hurd DD, Goy A, Schneider SE, Keppel CR, Wagner-Johnston ND, Carson KR, Bartlett NL. A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma. Blood. 2011 Nov 10;118(19):5119-25. Epub 2011 Sep 21. link to original article contains verified protocol link to PMC article PubMed

MINE

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MINE: Mesna, Ifosfamide, Novantrone (Mitoxantrone), Etoposide

Regimen

Study	Evidence
Rodriguez et al. 1995	Phase II

Chemotherapy

Mesna (Mesnex) 1.33 g/m² IV over 60 minutes once per day on days 1 to 3; mixed in same solution as Ifosfamide (Ifex)
- Mesna (Mesnex) 500 mg PO 4 hours after each IV dose of Ifosfamide (Ifex) once per day on days 1 to 3
Ifosfamide (Ifex) 1.33 g/m² IV over 60 minutes once per day on days 1 to 3; mixed in same solution as Mesna (Mesnex)
Mitoxantrone (Novantrone) 8 mg/m² IV once on day 1
Etoposide (Vepesid) 65 mg/m² IV over 60 minutes once per day on days 1 to 3

3 to 4-week cycle for up to 6 cycles in responding patients

References

Rodriguez MA, Cabanillas FC, Hagemeister FB, McLaughlin P, Romaguera JE, Swan F, Velasquez W. A phase II trial of mesna/ifosfamide, mitoxantrone and etoposide for refractory lymphomas. Ann Oncol. 1995 Jul;6(6):609-11. link to original article contains protocol PubMed

Mini-BEAM

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BEAM: BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan

Regimen #1

Study	Evidence
Fernández-Jiménez et al. 1999	Phase II

Chemotherapy

Carmustine (BiCNU) 60 mg/m² IV once on day 1
Etoposide (Vepesid) 300 mg/m² IV once on day 1
Cytarabine (Cytosar) 800 mg/m² IV once on day 1
Melphalan (Alkeran) 30 mg/m² IV once on day 1

28-day cycle for 2 to 3 cycles

Regimen #2

Study	Evidence
Colwill et al. 1995	Phase II

Chemotherapy

Carmustine (BiCNU) 60 mg/m² IV over 30 minutes once on day 1
Etoposide (Vepesid) 75 mg/m² IV over 30 minutes once per day on days 2 to 5
Cytarabine (Cytosar) 100 mg/m² IV Q12H on days 2 to 5
Melphalan (Alkeran) 30 mg/m² IV over 15 minutes once on day 6

Supportive medications

If febrile neutropenia occurred during previous cycle: Ciprofloxacin (Cipro) 500 mg PO once per day
Patients were transfused to keep Hb greater than or equal to 8 g/dL, platelets greater than or equal to 20 x 10⁹/L
There was no routine use of G-CSF or GM-CSF

4 to 6 week cycles, depending on hematologic recovery

Patients eligible for autologous hematopoietic cell transplant received no more than 2 cycles; otherwise total # of cycles not reported

References

Colwill R, Crump M, Couture F, Danish R, Stewart AK, Sutton DM, Scott JG, Sutcliffe SB, Brandwein JM, Keating A. Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease before intensive therapy and autologous bone marrow transplantation. J Clin Oncol. 1995 Feb;13(2):396-402. link to original article contains protocol PubMed
Fernández-Jiménez MC, Canales MA, Ojeda E, de Bustos JG, Aguado MJ, Hernández-Navarro F. Salvage chemotherapy with mini-BEAM for relapsed or refractory Hodgkin's disease prior to autologous peripheral blood stem cell transplantation. Haematologica. 1999 Nov;84(11):1007-11. link to original article contains verified protocol PubMed
1. Update: Martín A, Fernández-Jiménez MC, Caballero MD, Canales MA, Pérez-Simón JA, García de Bustos J, Vázquez L, Hernández-Navarro F, San Miguel JF. Long-term follow-up in patients treated with Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease. Br J Haematol. 2001 Apr;113(1):161-71. link to original article contains protocol PubMed

Nivolumab monotherapy

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Regimen #1, every 2 weeks

Study	Evidence
Younes et al. 2016	Phase II

Immunotherapy

Nivolumab (Opdivo) 3 mg/kg IV every 2 weeks

Continued until disease progression or treatment intolerance

Regimen #2, with lead-in

Study	Evidence
Ansell et al. 2014	Non-randomized

Immunotherapy

Nivolumab (Opdivo) 3 mg/kg IV once per week on week 1, week 4, and then every 2 weeks

Continued until disease progression, or complete response, or up to 2 years

References

Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, Rodig SJ, Chapuy B, Ligon AH, Zhu L, Grosso JF, Kim SY, Timmerman JM, Shipp MA, Armand P. PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma. N Engl J Med. 2015 Jan 22;372(4):311-9. Epub 2014 Dec 6. link to original article contains verified protocol link to PMC article PubMed
Younes A, Santoro A, Shipp M, Zinzani PL, Timmerman JM, Ansell S, Armand P, Fanale M, Ratanatharathorn V, Kuruvilla J, Cohen JB, Collins G, Savage KJ, Trneny M, Kato K, Farsaci B, Parker SM, Rodig S, Roemer MG, Ligon AH, Engert A. Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. 2016 Sep;17(9):1283-94. Epub 2016 Jul 20. link to original article contains protocol PubMed

O-ESHAP

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O-ESHAP: Ofatumumab, Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study	Evidence
Martínez et al. 2016 (GELTAMO)	Phase II

Note that the ofatumumab dosing is described in the abstract but the ESHAP is not. The ESHAP doses here are from the protocol defined by Velasquez et al. 1994.

Chemotherapy

Ofatumumab (Arzerra) as follows:
- Cycle 1: 1000 mg IV once per day on days 1 & 8
- Cycles 2 & 3: 1000 mg IV once on day 1
Etoposide (Vepesid) 40 mg/m² IV over 60 minutes once per day on days 1 to 4
Methylprednisolone (Solumedrol) 250 to 500 mg IV over 15 minutes once per day on days 1 to 5
Cytarabine (Cytosar) 2000 mg/m² IV over 2 hours once on day 5
Cisplatin (Platinol) 25 mg/m²/day IV continuous infusion on days 1 to 4 (total dose per cycle: 100 mg/m²)

Number of cycles not specified

References

Martínez C, Díaz-López A, Rodriguez-Calvillo M, García-Sanz R, Terol MJ, Pérez-Ceballos E, Jiménez MJ, Cantalapiedra A, Domingo-Domenech E, Rodriguez MJ, Sampol A, Espeso M, López FJ, Briones J, García JF, Sureda A; Hodgkin Lymphoma Subcommittee of Spanish Group of Lymphoma Bone Marrow Transplantation(GELTAMO). Phase II trial of ofatumumab plus ESHAP (O-ESHAP) as salvage treatment for patients with relapsed or refractory classical Hodgkin lymphoma after first-line chemotherapy. Br J Haematol. 2016 Sep;174(6):859-67. 2016 May 17. link to original article contains protocol PubMed

Panobinostat monotherapy

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Regimen

Study	Evidence	ORR	Pt Population
Younes et al. 2012	Phase II	Investigator assessment: 27% Central review: 22%	Progressed after auto HSCT and had a median of 4 prior systemic regimens (range 2 to 7)

Chemotherapy

Panobinostat (Farydak) 40 mg PO three times per week (e.g., MWF)

21-day cycles until progression or intolerance

References

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 verified protocol PubMed

Pembrolizumab monotherapy

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Regimen

Study	Evidence	Efficacy
Chen et al. 2017 (KEYNOTE-087)	Phase II	ORR: 69%

Immunotherapy

Pembrolizumab (Keytruda) 200 mg IV once on day 1

21-day cycles for up to 2 years

References

Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, Radford J, Ribrag V, Molin D, Vassilakopoulos TP, Tomita A, von Tresckow B, Shipp MA, Zhang Y, Ricart AD, Balakumaran A, Moskowitz CH; KEYNOTE-087. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol. 2017 Jul 1;35(19):2125-2132. Epub 2017 Apr 25. link to original article contains verified protocol PubMed

Rituximab monotherapy

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Regimen

Study	Evidence
Younes et al. 2003	Pilot, >20 pts

Patients had received a minimum of 2 prior systemic regimens. All reported patients had nodular sclerosis histology.

Chemotherapy

Rituximab (Rituxan) 375 mg/m² IV once per week

6-week course (6 doses total)

References

Younes A, Romaguera J, Hagemeister F, McLaughlin P, Rodriguez MA, Fiumara P, Goy A, Jeha S, Manning JT Jr, Jones D, Abruzzo LV, Medeiros LJ. A pilot study of rituximab in patients with recurrent, classic Hodgkin disease. Cancer. 2003 Jul 15;98(2):310-4. link to original article contains verified protocol PubMed

Sirolimus & Vorinostat

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Regimen

Study	Evidence
Janku et al. 2014	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.

Chemotherapy

Sirolimus (Rapamune) 4 mg PO once per day
Vorinostat (Zolinza) as follows:
- Cycle 1: 300 mg once per day on days 7 to 28
- Subsequent cycles: 300 mg once per day on days 1 to 28

28-day cycles

References

Abstract: Filip Janku, Yasuhiro Oki, Gerald Steven Falchook, Vivek Subbiah, Aung Naing, Vivianne Marie Velez Bravo, David S. Hong, Jason R. Westin, Cesar Nunez, Luis Fayad, Sattva Swarup Neelapu, Larry W. Kwak, Elizabeth J. Shpall, Jennifer J. Wheler, Tamara Barnes, Winnie S. Liang, Bodour Salhia, Funda Meric-Bernstam, Razelle Kurzrock, Michelle A. Fanale. Activity of the mTOR inhibitor sirolimus and HDAC inhibitor vorinostat in heavily pretreated refractory Hodgkin lymphoma patients. J Clin Oncol 32:5s, 2014 (suppl; abstr 8508) link to original abstract

Vinblastine monotherapy

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Regimen

Study	Evidence
Little et al. 1998	Retrospective

This is a retrospective study; we are not aware of a prospective trial of vinblastine monotherapy in this setting.

Chemotherapy

Vinblastine (Velban) 4 to 6 mg/m² IV once on day 1

1 to 2-week cycles

References

Retrospective: Little R, Wittes RE, Longo DL, Wilson WH. Vinblastine for recurrent Hodgkin's disease following autologous bone marrow transplant. J Clin Oncol. 1998 Feb;16(2):584-8. link to original article PubMed

Vinorelbine monotherapy

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Regimen

Study	Evidence
Devizzi et al. 1994	Phase II

Chemotherapy

Vinorelbine (Navelbine) 30 mg/m² IV bolus once per week

Complete responders received 6 additional doses past CR; others continued until progression or a maximum of 24 doses

References

Devizzi L, Santoro A, Bonfante V, Viviani S, Balzarini L, Valagussa P,vBonadonna G. Vinorelbine: an active drug for the management of patients withvheavily pretreated Hodgkin's disease. Ann Oncol. 1994 Nov;5(9):817-20. link to original article contains verified protocol PubMed

Consolidation and/or maintenance after salvage therapy

Allogeneic hematopoietic stem cell transplant

Usually reserved for patients relapsing after autologous HSCT, and then for younger and very fit individuals. The regimens below have been specifically studied in the setting of relapsed/refractory Hodgkin lymphoma.

Regimen #1

To be completed.

Preceding treatment

Salvage brentuximab vedotin

Regimen #2

Study	Evidence
Sureda et al. 2011	Phase II

Preceding treatment

DHAP x 2

Preparative regimen

Fludarabine (Fludara) 150 mg/m² IV once per day on days -8 to -4
Melphalan (Alkeran) 140 mg/m² IV once per day on days -3 & -2

Recipients of hematopoietic cells from matched unrelated donors also received:

Antithymocyte globulin (ATG) 45 mg/kg IV once per day on days -4 to -2

Graft-versus-host disease prophylaxis

Cyclosporine A (not specified whether modified or non-modified) starting on day -2 at 1.5 mg/kg IV BID
Methotrexate (MTX) 10 mg/m² IV once per day on days +1, +3, +6, +11

If no acute GVHD of grade 2 or more, cyclosporine A is tapered down by 10% per week starting on day +90 with planned discontinuation by day +180.

Regimen #3

Study	Evidence
Anderlini et al. 2008	Phase II

Patients had "chemosensitive or stable disease after salvage treatment." The regimen as reported here is what the authors were using towards the end of the study period; see paper for details.

Preparative regimen

Fludarabine (Fludara) 33 mg/m² IV once per day on days -5 to -2
Melphalan (Alkeran) 70 mg/m² IV once per day on days -3 & -2

Recipients of hematopoietic cells from matched unrelated donors also received:

Antithymocyte globulin (ATG) 2 mg/kg IV once per day on days -4 to -2

Graft-versus-host disease prophylaxis

Tacrolimus (Prograf) IV starting on day -2, dosed to achieve serum levels 4–12 ng/mL and switched to PO as soon as possible. Continued for at least 6 months and then "tapered off" (instructions not given).
Methotrexate (MTX) 5 mg/m² IV once per day on days +1, +3, +6 (extra dose on day +11 for MUD recipients)

Regimen #4

Study	Evidence
Sobol et al. 2013	Phase II

BEAM is the preparative regimen; further details not available in the abstract.

References

Alvarez I, Sureda A, Caballero MD, Urbano-Ispizua A, Ribera JM, Canales M, García-Conde J, Sanz G, Arranz R, Bernal MT, de la Serna J, Díez JL, Moraleda JM, Rubió-Félix D, Xicoy B, Martínez C, Mateos MV, Sierra J. Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol. Biol Blood Marrow Transplant. 2006 Feb;12(2):172-83. link to original article contains protocol PubMed
Anderlini P, Saliba R, Acholonu S, Giralt SA, Andersson B, Ueno NT, Hosing C, Khouri IF, Couriel D, de Lima M, Qazilbash MH, Pro B, Romaguera J, Fayad L, Hagemeister F, Younes A, Munsell MF, Champlin RE. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin's lymphoma: the updated M.D. Anderson Cancer Center experience. Haematologica. 2008 Feb;93(2):257-64. Epub 2008 Jan 26. link to original article contains verified protocol link to PMC article PubMed
Sureda A, Canals C, Arranz R, Caballero D, Ribera JM, Brune M, Passweg J, Martino R, Valcárcel D, Besalduch J, Duarte R, León A, Pascual MJ, García-Noblejas A, López Corral L, Xicoy B, Sierra J, Schmitz N. Allogeneic stem cell transplantation after reduced intensity conditioning in patients with relapsed or refractory Hodgkin's lymphoma. Results of the HDR-ALLO study - a prospective clinical trial by the Grupo Español de Linfomas/Trasplante de Médula Osea (GEL/TAMO) and the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2012 Feb;97(2):310-7. Epub 2011 Oct 11. link to original article contains verified protocol link to PMC article PubMed
Sobol U, Rodriguez T, Smith S, Go A, Vimr R, Parthasarathy M, Guo R, Stiff P. Seven-year follow-up of allogeneic transplant using BCNU, etoposide, cytarabine and melphalan chemotherapy in patients with Hodgkin lymphoma after autograft failure: importance of minimal residual disease. Leuk Lymphoma. 2014 Jun;55(6):1281-7. Epub 2013 Oct 3. link to original article PubMed
Illidge T, Bouabdallah R, Chen R, Gopal AK, Moskowitz CH, Ramchandren R, Shustov AR, Tilly H, Trippett TM, Gibb A, Grove LE, Advani R. Allogeneic transplant following brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Leuk Lymphoma. 2015 Mar;56(3):703-10. Epub 2015 Jan 21 link to original article PubMed

Autologous hematopoietic stem cell transplant

To be completed. Usually preceded by a high-intensity salvage chemotherapy.

Patients in AETHERA were subsequently randomized to brentuximab vedotin maintenance versus observation.

References

Morschhauser F, Brice P, Fermé C, Diviné M, Salles G, Bouabdallah R, Sebban C, Voillat L, Casasnovas O, Stamatoullas A, Bouabdallah K, André M, Jais JP, Cazals-Hatem D, Gisselbrecht C; GELA/SFGM Study Group. Risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation for first relapse/refractory Hodgkin's lymphoma: results of the prospective multicenter H96 trial by the GELA/SFGM study group. J Clin Oncol. 2008 Dec 20;26(36):5980-7. Epub 2008 Nov 17. link to original article PubMed
1. Update: Sibon D, Morschhauser F, Resche-Rigon M, Ghez D, Dupuis J, Marçais A, Deau-Fischer B, Bouabdallah R, Sebban C, Salles G, Brice P. Single or tandem autologous stem-cell transplantation for first-relapsed or refractory Hodgkin lymphoma: 10-year follow-up of the prospective H96 trial by the LYSA/SFGM-TC study group. Haematologica. 2016 Apr;101(4):474-81. Epub 2015 Dec 31. link to original article link to PMC article PubMed
Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A, Osmanov D, Bachanova V, Sweetenham J, Sureda A, Huebner D, Sievers EL, Chi A, Larsen EK, Hunder NN, Walewski J; AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 May 9;385(9980):1853-62. Epub 2015 Mar 18. Erratum in: Lancet. 2015 Aug 8;386(9993):532. link to original article contains verified protocol PubMed

Brentuximab vedotin monotherapy

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Regimen

Study	Evidence	Comparator	Efficacy
Moskowitz et al. 2015 (AETHERA)	Phase III	Placebo	Superior PFS

Treatment begins 30 to 45 days after transplant.

Preceding treatment

Autologous HSCT

Chemotherapy

Brentuximab vedotin (Adcetris) 1.8 mg/kg IV once on day 1

21-day cycle for 16 cycles

References

Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A, Osmanov D, Bachanova V, Sweetenham J, Sureda A, Huebner D, Sievers EL, Chi A, Larsen EK, Hunder NN, Walewski J; AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 May 9;385(9980):1853-62. Epub 2015 Mar 18. Erratum in: Lancet. 2015 Aug 8;386(9993):532. link to original article contains verified protocol PubMed

Observation

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Regimen

Study	Evidence	Comparator	Efficacy
Moskowitz et al. 2015 (AETHERA)	Phase III	Brentuximab vedotin	Inferior PFS

No further treatment after autologous HSCT.

References

Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A, Osmanov D, Bachanova V, Sweetenham J, Sureda A, Huebner D, Sievers EL, Chi A, Larsen EK, Hunder NN, Walewski J; AETHERA Study Group. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 May 9;385(9980):1853-62. Epub 2015 Mar 18. Erratum in: Lancet. 2015 Aug 8;386(9993):532. link to original article contains verified protocol PubMed

Radiation therapy

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RT: Radiation Therapy

Regimen #1, involved node RT (INRT)

Study	Evidence
Raemaekers et al. 2014 (EORTC/LYSA/FIL H10)	Non-randomized portion of RCT

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.

Preceding treatment

eBEACOPP x 2

Radiotherapy

30 Gy (+ 6 Gy boost)

Regimen #2, involved field RT (IFRT)

Study	Evidence
Radford et al. 2015 (UK NCRI RAPID)	Non-randomized portion of RCT

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.

Preceding treatment

ABVD x 4

Radiotherapy

30 Gy

References

Raemaekers JM, André MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Fermé C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. Epub 2014 Mar 17. link to original article contains protocol PubMed
Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P, Wimperis J, Culligan D, Popova B, Smith P, McMillan A, Brownell A, Kruger A, Lister A, Hoskin P, O'Doherty M, Barrington S. Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma. N Engl J Med. 2015 Apr 23;372(17):1598-607. link to original article contains protocol PubMed

Response criteria

NCI Sponsored International Working Group Criteria (1999)

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Intended for non-Hodgkin lymphoma (NHL) but often referred to in the Hodgkin lymphoma literature.

Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. link to original article PubMed

International Harmonization Project on Lymphoma (2007)

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Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. Epub 2007 Jan 22. link to original article PubMed

Juweid's criteria (2007)

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Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, Wiseman GA, Kostakoglu L, Scheidhauer K, Buck A, Naumann R, Spaepen K, Hicks RJ, Weber WA, Reske SN, Schwaiger M, Schwartz LH, Zijlstra JM, Siegel BA, Cheson BD; Imaging Subcommittee of International Harmonization Project in Lymphoma. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007 Feb 10;25(5):571-8. Epub 2007 Jan 22. link to original article PubMed

Deauville criteria (2009)

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Note: the definition of "positive" versus "negative" varies and should be confirmed within individual protocols. This is a 5-point scale.

1: no residual FDG uptake above the background level
2: residual FDG uptake less than or equal to the mediastinum
3: residual FDG uptake greater than the mediastinum but not greater than the liver
4: residual FDG uptake moderately increased compared with the liver
5: residual FDG uptake markedly increased compared with the liver or new sites of disease.

References

Meignan M, Gallamini A, Meignan M, Gallamini A, Haioun C. Report on the First International Workshop on Interim-PET-Scan in Lymphoma. Leuk Lymphoma. 2009 Aug;50(8):1257-60. link to original article PubMed
Barrington SF, Qian W, Somer EJ, Franceschetto A, Bagni B, Brun E, Almquist H, Loft A, Højgaard L, Federico M, Gallamini A, Smith P, Johnson P, Radford J, O'Doherty MJ. Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma. Eur J Nucl Med Mol Imaging. 2010 Oct;37(10):1824-33. Epub 2010 May 27. link to original article PubMed
Biggi A, Gallamini A, Chauvie S, Hutchings M, Kostakoglu L, Gregianin M, Meignan M, Malkowski B, Hofman MS, Barrington SF. International validation study for interim PET in ABVD-treated, advanced-stage hodgkin lymphoma: interpretation criteria and concordance rate among reviewers. J Nucl Med. 2013 May;54(5):683-90. Epub 2013 Mar 20. link to original article PubMed

Investigational agents

Fotemustine (Muphoran)

@@ Line 36: / Line 36: @@
 |-
 |[http://jco.ascopubs.org/content/25/23/3495.long Engert et al. 2007 (GHSG HD7)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |No chemotherapy
-|style="background-color:#1a9850"|Superior FFTF
+| style="background-color:#1a9850" |Superior FFTF
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1000067 Engert et al. 2010 (GHSG HD10)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |ABVD x 4
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
-|rowspan=3|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61469-0/fulltext Behringer et al. 2014 (GHSG HD13)]
+| rowspan="3" |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61469-0/fulltext Behringer et al. 2014 (GHSG HD13)]
-|rowspan=3 style="background-color:#1a9851"|Phase III
+| rowspan="3" style="background-color:#1a9851" |Phase III
 |ABV
-|style="background-color:#1a9850"|Superior FFTF
+| style="background-color:#1a9850" |Superior FFTF
 |-
 |AV
-|style="background-color:#1a9850"|Superior FFTF
+| style="background-color:#1a9850" |Superior FFTF
 |-
 |[[#AVD|AVD]]
-|style="background-color:#d9ef8b"|Might have superior FFTF
+| style="background-color:#d9ef8b" |Might have superior FFTF
 |-
 |}
@@ Line 78: / Line 78: @@
 |-
 |[http://jco.ascopubs.org/content/32/12/1188.long Raemaekers et al. 2014 (EORTC/LYSA/FIL H10 F)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC.2FLYSA.2FFIL_H10|See link]]
 |[[Complex_multipart_regimens#EORTC.2FLYSA.2FFIL_H10|See link]]
@@ Line 101: / Line 101: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1408648 Radford et al. 2015 (UK NCRI RAPID)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
@@ Line 123: / Line 123: @@
 |-
 |[http://jco.ascopubs.org/content/22/14/2835.long Bonadonna et al. 2004]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1000067 Engert et al. 2010 (GHSG HD10)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |ABVD x 2
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932020/ Meyer et al. 2011 (NCIC CTG/ECOG HD.6)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#Radiation_therapy|STNI]]
-|style="background-color:#91cf60"|Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
@@ Line 178: / Line 178: @@
 ![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|rowspan=3|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61469-0/fulltext Behringer et al. 2014 (GHSG HD13)]
+| rowspan="3" |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61469-0/fulltext Behringer et al. 2014 (GHSG HD13)]
-|rowspan=3 style="background-color:#1a9851"|Phase III
+| rowspan="3" style="background-color:#1a9851" |Phase III
 |ABV
-|style="background-color:#d3d3d3"|Not reported
+| style="background-color:#d3d3d3" |Not reported
 |-
 |[[#ABVD|ABVD]]
-|style="background-color:#fee08b"|Might have inferior FFTF
+| style="background-color:#fee08b" |Might have inferior FFTF
 |-
 |AV
-|style="background-color:#d3d3d3"|Not reported
+| style="background-color:#d3d3d3" |Not reported
 |-
 |}
@@ Line 217: / Line 217: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa064601 Fermé et al. 2007 (EORTC-GELA H8-F)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC-GELA_H8-F|See link]]
 |[[Complex_multipart_regimens#EORTC-GELA_H8-F|See link]]
@@ Line 253: / Line 253: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932020/ Meyer et al. 2011 (NCIC CTG/ECOG HD.6)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#ABVD|ABVD]]
-|style="background-color:#fc8d59"|Seems to have inferior OS
+| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |}
@@ Line 269: / Line 269: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa064601 Fermé et al. 2007 (EORTC-GELA H8-F)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#MOPP-ABV|MOPP-ABV]], then [[#Radiation_therapy_2|IFRT]]
-|style="background-color:#d73027"|Inferior OS
+| style="background-color:#d73027" |Inferior OS
 |-
 |}
@@ Line 293: / Line 293: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603439/ Advani et al. 2013 (G4)]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
 |-
 |}
@@ Line 333: / Line 333: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932020/ Meyer et al. 2011 (NCIC CTG/ECOG HD.6)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#NCIC_CTG.2FECOG_HD.6|See link]]
 |[[Complex_multipart_regimens#NCIC_CTG.2FECOG_HD.6|See link]]
@@ Line 361: / Line 361: @@
 |-
 |[http://jco.ascopubs.org/content/32/12/1188.long Raemaekers et al. 2014 (EORTC/LYSA/FIL H10 U)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC.2FLYSA.2FFIL_H10|See link]]
 |[[Complex_multipart_regimens#EORTC.2FLYSA.2FFIL_H10|See link]]
@@ Line 387: / Line 387: @@
 |-
 |[http://jco.ascopubs.org/content/28/27/4199.long Eich et al. 2010 (GHSG HD11)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#GHSG_HD11|See link]]
 |[[Complex_multipart_regimens#GHSG_HD11|See link]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932020/ Meyer et al. 2011 (NCIC CTG/ECOG HD.6)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |ABVD x 2, then [[#Radiation_therapy_2|STNI]]
-|style="background-color:#91cf60"|Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |[http://jco.ascopubs.org/content/30/9/907.long von Tresckow et al. 2012 (GHSG HD14)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#GHSG_HD14|See link]]
 |[[Complex_multipart_regimens#GHSG_HD14|See link]]
@@ Line 421: / Line 421: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451176/ Advani et al. 2015 (ECOG E2496)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#Stanford_V_2|Stanford V]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
@@ Line 462: / Line 462: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025897/ Kumar et al. 2016]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 496: / Line 496: @@
 |-
 |[http://jco.ascopubs.org/content/28/27/4199.long Eich et al. 2010 (GHSG HD11)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#GHSG_HD11|See link]]
 |[[Complex_multipart_regimens#GHSG_HD11|See link]]
@@ Line 533: / Line 533: @@
 |-
 |[http://jco.ascopubs.org/content/30/9/907.long von Tresckow et al. 2012 (GHSG HD14)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#GHSG_HD14|See link]]
 |[[Complex_multipart_regimens#GHSG_HD14|See link]]
@@ Line 574: / Line 574: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa064601 Fermé et al. 2007 (EORTC-GELA H8-U)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC-GELA_H8-U|See link]]
 |[[Complex_multipart_regimens#EORTC-GELA_H8-U|See link]]
@@ Line 600: / Line 600: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa064601 Fermé et al. 2007 (EORTC-GELA H8-U)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC-GELA_H8-U|See link]]
 |[[Complex_multipart_regimens#EORTC-GELA_H8-U|See link]]
@@ Line 633: / Line 633: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359734/ Kasamon et al. 2012]
-|style="background-color:#ffffbe"|Phase II, <20 pts in subgroup
+| style="background-color:#ffffbe" |Phase II, <20 pts in subgroup
 |-
 |}
@@ Line 665: / Line 665: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451176/ Advani et al. 2015 (ECOG E2496)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#ABVD_2|ABVD]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
@@ Line 708: / Line 708: @@
 |-
 |[http://jco.ascopubs.org/content/34/12/1376.full Zinzani et al. 2016 (HD0801)]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966513/ Press et al. 2016 (SWOG S0816)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961236/ Johnson et al. 2016 (RATHL)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
@@ Line 740: / Line 740: @@
 |-
 |[http://jco.ascopubs.org/content/34/12/1376.full Zinzani et al. 2016 (HD0801)]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966513/ Press et al. 2016 (SWOG S0816)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961236/ Johnson et al. 2016 (RATHL)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1708984 Connors et al. 2017 (ECHELON-1)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#A+AVD_2|A+AVD]]
-|style="background-color:#fc8d59"|Seems to have inferior modified PFS
+| style="background-color:#fc8d59" |Seems to have inferior modified PFS
 |-
 |}
@@ Line 782: / Line 782: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pubmed/54209 Bonadonna et al. 1975]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#MOPP|MOPP]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |[http://jco.ascopubs.org/content/5/1/27.long Santoro et al. 1987]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#MOPP|MOPP]]
-|style="background-color:#91cf60"|Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS
 |-
-|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJM199211193272102 Canellos et al. 1992]
+| rowspan="2" |[http://www.nejm.org/doi/full/10.1056/NEJM199211193272102 Canellos et al. 1992]
-|rowspan=2 style="background-color:#1a9851"|Phase III
+| rowspan="2" style="background-color:#1a9851" |Phase III
 |[[#MOPP|MOPP]]
-|style="background-color:#1a9850"|Superior FFS
+| style="background-color:#1a9850" |Superior FFS
 |-
 |[[#MOPP.2FABVD|MOPP/ABVD]]
-|style="background-color:#d3d3d3"|Not reported
+| style="background-color:#d3d3d3" |Not reported
 |-
 |[http://jco.ascopubs.org/content/27/32/5390.long Hoskin et al. 2009 (UK NCRI ISRCTN 64141244)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#Stanford_V_2|Stanford V]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1100340 Viviani et al. 2011]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#Escalated_BEACOPP_2|Escalated BEACOPP]], then [[#BEACOPP_2|BEACOPP]]
-|style="background-color:#fc8d59"|Seems to have inferior FFFP
+| style="background-color:#fc8d59" |Seems to have inferior FFFP
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574266/ Gordon et al. 2013 (E2496)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#Stanford_V_2|Stanford V]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |[http://annonc.oxfordjournals.org/content/25/8/1622.full.html Mounier et al. 2014 (LYSA H34)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#Escalated_BEACOPP_2|Escalated BEACOPP]], then [[#BEACOPP_2|BEACOPP]]
-|style="background-color:#fee08b"|Might have inferior EFS
+| style="background-color:#fee08b" |Might have inferior EFS
 |-
 |[http://jco.ascopubs.org/content/34/17/2028.full Carde et al. 2016 (EORTC 20012)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#Escalated_BEACOPP_2|Escalated BEACOPP]], then [[#BEACOPP_2|BEACOPP]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
@@ Line 868: / Line 868: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.12862/full Russo et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 902: / Line 902: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961236/ Johnson et al. 2016 (RATHL)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#ABVD_3|ABVD]]
-|style="background-color:#ffffbf"|Inconclusive whether non-inferior
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior
 |-
 |}
@@ Line 935: / Line 935: @@
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70501-1/fulltext Younes et al. 2013]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1708984 Connors et al. 2017 (ECHELON-1)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#ABVD_3|ABVD]]
-|style="background-color:#91cf60"|Seems to have superior modified PFS
+| style="background-color:#91cf60" |Seems to have superior modified PFS
 |-
 |}
@@ Line 981: / Line 981: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1100340 Viviani et al. 2011]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#Viviani_et_al._2011_.28IIL.29|See link]]
 |[[Complex_multipart_regimens#Viviani_et_al._2011_.28IIL.29|See link]]
 |-
 |[http://jco.ascopubs.org/content/29/32/4234.long Borchmann et al. 2011 (GHSG HD12)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#GHSG_HD12|See link]]
 |[[Complex_multipart_regimens#GHSG_HD12|See link]]
 |-
 |[http://annonc.oxfordjournals.org/content/25/8/1622.full.html Mounier et al. 2014 (LYSA H34)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#LYSA_H34|See link]]
 |[[Complex_multipart_regimens#LYSA_H34|See link]]
 |-
 |[http://jco.ascopubs.org/content/34/17/2028.full Carde et al. 2016 (EORTC 20012)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC_20012|See link]]
 |[[Complex_multipart_regimens#EORTC_20012|See link]]
@@ Line 1,028: / Line 1,028: @@
 |-
 |[http://annonc.oxfordjournals.org/content/8/2/143.long Diehl et al. 1997]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
-|rowspan=2|[http://jco.ascopubs.org/content/16/12/3810.long Diehl et al. 1998 (GHSG HD9)]
+| rowspan="2" |[http://jco.ascopubs.org/content/16/12/3810.long Diehl et al. 1998 (GHSG HD9)]
-|rowspan=2 style="background-color:#1a9851"|Phase III
+| rowspan="2" style="background-color:#1a9851" |Phase III
 |[[#Escalated_BEACOPP_2|Escalated dose BEACOPP]]
-|style="background-color:#d73027"|Inferior FFTF
+| style="background-color:#d73027" |Inferior FFTF
 |-
 |[[Hodgkin_lymphoma_-_historical#COPP.2FABVD|COPP/ABVD]]
-|style="background-color:#91cf60"|Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
@@ Line 1,079: / Line 1,079: @@
 |-
 |[http://jco.ascopubs.org/content/21/9/1734.full Sieber et al. 2003]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
-|rowspan=2|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61940-5/fulltext Engert et al. 2012 (GHSG HD15)]
+| rowspan="2" |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61940-5/fulltext Engert et al. 2012 (GHSG HD15)]
-|rowspan=2 style="background-color:#1a9851"|Phase III
+| rowspan="2" style="background-color:#1a9851" |Phase III
 |[[#Escalated_BEACOPP_2|Escalated BEACOPP x 8]]
-|style="background-color:#d3d3d3"|Not reported
+| style="background-color:#d3d3d3" |Not reported
 |-
 |[[#Escalated_BEACOPP_2|Escalated BEACOPP x 6]]
-|style="background-color:#eeee01"|Non-inferior FFTF
+| style="background-color:#eeee01" |Non-inferior FFTF
 |-
 |}
@@ Line 1,125: / Line 1,125: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0142(20000501)88:9%3C2142::AID-CNCR21%3E3.0.CO;2-M/full Montoto et al. 2000]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 1,158: / Line 1,158: @@
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30103-1/fulltext Borchmann et al. 2017 (GHSG HD18)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
@@ Line 1,186: / Line 1,186: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1100340 Viviani et al. 2011]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#Viviani_et_al._2011_.28IIL.29|See link]]
 |[[Complex_multipart_regimens#Viviani_et_al._2011_.28IIL.29|See link]]
 |-
 |[http://jco.ascopubs.org/content/29/32/4234.long Borchmann et al. 2011 (GHSG HD12)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#GHSG_HD12|See link]]
 |[[Complex_multipart_regimens#GHSG_HD12|See link]]
 |-
 |[http://annonc.oxfordjournals.org/content/25/8/1622.full.html Mounier et al. 2014 (LYSA H34)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#LYSA_H34|See link]]
 |[[Complex_multipart_regimens#LYSA_H34|See link]]
 |-
 |[http://jco.ascopubs.org/content/34/17/2028.full Carde et al. 2016 (EORTC 20012)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC_20012|See link]]
 |[[Complex_multipart_regimens#EORTC_20012|See link]]
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30103-1/fulltext Borchmann et al. 2017 (GHSG HD18)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |eBEACOPP x 6<br> eBEACOPP x 8
-|style="background-color:#eeee01"|Non-inferior PFS (*)
+| style="background-color:#eeee01" |Non-inferior PFS (*)
 |-
 |}
@@ Line 1,235: / Line 1,235: @@
 ![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|rowspan=2|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61940-5/fulltext Engert et al. 2012 (GHSG HD15)]
+| rowspan="2" |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61940-5/fulltext Engert et al. 2012 (GHSG HD15)]
-|rowspan=2 style="background-color:#1a9851"|Phase III
+| rowspan="2" style="background-color:#1a9851" |Phase III
 |[[#BEACOPP-14|BEACOPP-14]]
-|style="background-color:#eeee01"|Non-inferior FFTF
+| style="background-color:#eeee01" |Non-inferior FFTF
 |-
 |Escalated BEACOPP x 8
-|style="background-color:#91cf60"|Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30103-1/fulltext Borchmann et al. 2017 (GHSG HD18)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |eBEACOPP x 4<br> eBEACOPP x 8
-|style="background-color:#eeee01"|Non-inferior PFS (*)
+| style="background-color:#eeee01" |Non-inferior PFS (*)
 |-
 |}
@@ Line 1,268: / Line 1,268: @@
 ![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|rowspan=2|[http://jco.ascopubs.org/content/16/12/3810.long Diehl et al. 1998 (GHSG HD9)]
+| rowspan="2" |[http://jco.ascopubs.org/content/16/12/3810.long Diehl et al. 1998 (GHSG HD9)]
-|rowspan=2 style="background-color:#1a9851"|Phase III
+| rowspan="2" style="background-color:#1a9851" |Phase III
 |[[#BEACOPP_2|BEACOPP]]
-|style="background-color:#1a9850"|Superior FFTF
+| style="background-color:#1a9850" |Superior FFTF
 |-
 |[[Hodgkin_lymphoma_-_historical#COPP.2FABVD|COPP/ABVD]]
-|style="background-color:#91cf60"|Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |[http://jco.ascopubs.org/content/29/32/4234.long Borchmann et al. 2011 (GHSG HD12)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#GHSG_HD12|See link]]
 |[[Complex_multipart_regimens#GHSG_HD12|See link]]
 |-
-|rowspan=2|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61940-5/fulltext Engert et al. 2012 (GHSG HD15)]
+| rowspan="2" |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61940-5/fulltext Engert et al. 2012 (GHSG HD15)]
-|rowspan=2 style="background-color:#1a9851"|Phase III
+| rowspan="2" style="background-color:#1a9851" |Phase III
 |[[#BEACOPP-14|BEACOPP-14]]
-|style="background-color:#d3d3d3"|Not reported
+| style="background-color:#d3d3d3" |Not reported
 |-
 |Escalated BEACOPP x 6
-|style="background-color:#fc8d59"|Seems to have inferior OS
+| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30103-1/fulltext Borchmann et al. 2017 (GHSG HD18)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |eBEACOPP x 4<br> eBEACOPP x 6
-|style="background-color:#eeee01"|Non-inferior PFS (*)
+| style="background-color:#eeee01" |Non-inferior PFS (*)
 |-
 |}
@@ Line 1,336: / Line 1,336: @@
 |-
 |[http://jco.ascopubs.org/content/12/2/279.long Somers et al. 1994]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#MOPP.2FABVD|MOPP/ABVD]]
-|style="background-color:#fc8d59"|Seems to have inferior FFS
+| style="background-color:#fc8d59" |Seems to have inferior FFS
 |-
 |}
@@ Line 1,356: / Line 1,356: @@
 ![[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJM199211193272102 Canellos et al. 1992]
+| rowspan="2" |[http://www.nejm.org/doi/full/10.1056/NEJM199211193272102 Canellos et al. 1992]
-|rowspan=2 style="background-color:#1a9851"|Phase III
+| rowspan="2" style="background-color:#1a9851" |Phase III
 |[[#ABVD_3|ABVD]]
-|style="background-color:#d73027"|Inferior FFS
+| style="background-color:#d73027" |Inferior FFS
 |-
 |[[#MOPP.2FABVD|MOPP/ABVD]]
-|style="background-color:#fc8d59"|Seems to have inferior FFS
+| style="background-color:#fc8d59" |Seems to have inferior FFS
 |-
 |}
@@ Line 1,381: / Line 1,381: @@
 |-
 |[http://annals.org/article.aspx?articleid=684972 Devita et al. 1970]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(197507)36:1%3C252::AID-CNCR2820360128%3E3.0.CO;2-7/abstract Bonadonna et al. 1975]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#ABVD_5|ABVD]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
-|rowspan=3|[http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract Cooper et al. 1980]
+| rowspan="3" |[http://onlinelibrary.wiley.com/doi/10.1002/1097-0142(19800815)46:4%3C654::AID-CNCR2820460405%3E3.0.CO;2-A/abstract Cooper et al. 1980]
-|rowspan=3 style="background-color:#1a9851"|Phase III
+| rowspan="3" style="background-color:#1a9851" |Phase III
 |[[Hodgkin_lymphoma_-_historical#COPP|COPP]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |[[Hodgkin_lymphoma_-_historical#CVPP|CVPP]]
-|style="background-color:#fc8d59"|Seems to have inferior CR rate
+| style="background-color:#fc8d59" |Seems to have inferior CR rate
 |-
 |[[Hodgkin_lymphoma_-_historical#MVPP|MVPP]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJM198204013061303 Santoro et al. 1982]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#MOPP.2FABVD|MOPP/ABVD]]
-|style="background-color:#d73027"|Inferior PFS
+| style="background-color:#d73027" |Inferior PFS
 |-
 |[http://jco.ascopubs.org/content/5/1/27.long Santoro et al. 1987]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#ABVD_3|ABVD]]
-|style="background-color:#fc8d59"|Seems to have inferior OS
+| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |[http://jco.ascopubs.org/content/9/8/1409.long Longo et al. 1991]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |MOPP/CABS
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
@@ Line 1,451: / Line 1,451: @@
 |-
 |[http://jco.ascopubs.org/content/3/9/1174.abstract Klimo et al. 1985]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://jco.ascopubs.org/content/16/1/19.abstract Glick et al. 1998]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |MOPP, then ABVD
-|style="background-color:#91cf60"|Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |[http://jco.ascopubs.org/content/21/4/607.long Duggan et al. 2003]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#ABVD_3|ABVD]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
@@ Line 1,497: / Line 1,497: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJM198204013061303 Santoro et al. 1982]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#MOPP|MOPP]]
-|style="background-color:#1a9850"|Superior PFS
+| style="background-color:#1a9850" |Superior PFS
 |-
-|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJM199211193272102 Canellos et al. 1992]
+| rowspan="2" |[http://www.nejm.org/doi/full/10.1056/NEJM199211193272102 Canellos et al. 1992]
-|rowspan=2 style="background-color:#1a9851"|Phase III
+| rowspan="2" style="background-color:#1a9851" |Phase III
 |[[#ABVD_3|ABVD]]
-|style="background-color:#d3d3d3"|Not reported
+| style="background-color:#d3d3d3" |Not reported
 |-
 |[[#MOPP|MOPP]]
-|style="background-color:#91cf60"|Seems to have superior FFS
+| style="background-color:#91cf60" |Seems to have superior FFS
 |-
 |[http://jco.ascopubs.org/content/12/2/279.long Somers et al. 1994]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#MOPP|MOPP]]
-|style="background-color:#91cf60"|Seems to have superior FFS
+| style="background-color:#91cf60" |Seems to have superior FFS
 |-
 |}
@@ Line 1,540: / Line 1,540: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359733/ Younes et al. 2012]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 1,558: / Line 1,558: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359734/ Kasamon et al. 2012]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 1,590: / Line 1,590: @@
 |-
 |[http://jco.ascopubs.org/content/27/32/5390.long Hoskin et al. 2009 (UK NCRI ISRCTN 64141244)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#ABVD_3|ABVD]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574266/ Gordon et al. 2013 (ECOG E2496)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#ABVD_3|ABVD]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
@@ Line 1,656: / Line 1,656: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pubmed/10526668 Viviani et al. 1999]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 1,684: / Line 1,684: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (AHOD0031)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
@@ Line 1,707: / Line 1,707: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (COG P9425)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 1,733: / Line 1,733: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (AHOD0031)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
@@ Line 1,759: / Line 1,759: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (COG P9425)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 1,795: / Line 1,795: @@
 |-
 |[http://jco.ascopubs.org/content/28/23/3680.long Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 1,826: / Line 1,826: @@
 |-
 |[http://jco.ascopubs.org/content/28/23/3680.long Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 1,859: / Line 1,859: @@
 |-
 |[http://annonc.oxfordjournals.org/content/16/1/124.long Ballova et al. 2005 (GHSG HD9elderly)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Hodgkin_lymphoma_-_historical#COPP.2FABVD|COPP/ABVD]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
@@ Line 1,891: / Line 1,891: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692140/ Forero-Torres et al. 2015]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#f7fcfd"|ORR: 92%
+| style="background-color:#f7fcfd" |ORR: 92%
 |-
 |}
@@ Line 1,909: / Line 1,909: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4692140/ Forero-Torres et al. 2015]
-|style="background-color:#ffffbe"|Phase II, <20 pts in this subgroup
+| style="background-color:#ffffbe" |Phase II, <20 pts in this subgroup
 |-
 |}
@@ Line 1,938: / Line 1,938: @@
 |-
 |[http://www.bloodjournal.org/content/130/26/2829.long Friedberg et al. 2017]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#f7fcfd"|ORR: 100%
+| style="background-color:#f7fcfd" |ORR: 100%
 |-
 |}
@@ Line 1,957: / Line 1,957: @@
 |-
 |[http://www.bloodjournal.org/content/130/26/2829.long Friedberg et al. 2017]
-|style="background-color:#ffffbe"|Phase II, <20 pts in this subgroup
+| style="background-color:#ffffbe" |Phase II, <20 pts in this subgroup
-|style="background-color:#f7fcfd"|ORR: 100%
+| style="background-color:#f7fcfd" |ORR: 100%
 |-
 |}
@@ Line 1,984: / Line 1,984: @@
 |-
 |[http://annonc.oxfordjournals.org/content/6/2/167.long International ChIVPP Treatment Group 1995]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,013: / Line 2,013: @@
 |-
 |[http://www.bloodjournal.org/content/118/24/6292.long Böll et al. 2011]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,044: / Line 2,044: @@
 |-
 |[http://jco.ascopubs.org/content/28/23/3680.long Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,063: / Line 2,063: @@
 |-
 |[http://jco.ascopubs.org/content/28/23/3680.long Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,092: / Line 2,092: @@
 |-
 |[http://jco.ascopubs.org/content/28/23/3680.long Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,111: / Line 2,111: @@
 |-
 |[http://jco.ascopubs.org/content/28/23/3680.long Mauz-Körholz et al. 2010 (GPOH-HD-2002)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,139: / Line 2,139: @@
 |-
 |[http://jco.ascopubs.org/content/29/32/4234.long Borchmann et al. 2011 (GHSG HD12)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#GHSG_HD12|See link]]
 |[[Complex_multipart_regimens#GHSG_HD12|See link]]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1408648 Radford et al. 2015 (UK NCRI RAPID)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#Radiation_therapy_2|IFRT]]
-|style="background-color:#ffffbf"|Inconclusive whether non-inferior
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior
 |-
 |}
@@ Line 2,173: / Line 2,173: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1000067 Engert et al. 2010 (GHSG HD10)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |IFRT x 30 Gy
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |[http://jco.ascopubs.org/content/28/27/4199.long Eich et al. 2010 (GHSG HD11)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#GHSG_HD11|See link]]
 |[[Complex_multipart_regimens#GHSG_HD11|See link]]
@@ Line 2,197: / Line 2,197: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744567/ Schwartz et al. 2009 (COG P9425)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4220044/ Friedman et al. 2014 (AHOD0031)]
-|style="background-color:#1a9851"|Phase III (C)
+| style="background-color:#1a9851" |Phase III (C)
 |[[#Observation|Observation]]
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
@@ Line 2,223: / Line 2,223: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1000067 Engert et al. 2010 (GHSG HD10)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |IFRT x 20 Gy
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |[http://jco.ascopubs.org/content/28/27/4199.long Eich et al. 2010 (GHSG HD11)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#GHSG_HD11|See link]]
 |[[Complex_multipart_regimens#GHSG_HD11|See link]]
 |-
 |[http://jco.ascopubs.org/content/30/9/907.long von Tresckow et al. 2012 (GHSG HD14)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#GHSG_HD14|See link]]
 |[[Complex_multipart_regimens#GHSG_HD14|See link]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603439/ Advani et al. 2013 (G4)]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61469-0/fulltext Behringer et al. 2014 (GHSG HD13)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1408648 Radford et al. 2015 (UK NCRI RAPID)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#Observation|No further treatment]]
-|style="background-color:#ffffbf"|Inconclusive whether non-inferior
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior
 |-
 |}
@@ Line 2,271: / Line 2,271: @@
 |-
 |[http://jco.ascopubs.org/content/29/32/4234.long Borchmann et al. 2011 (GHSG HD12)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#GHSG_HD12|See link]]
 |[[Complex_multipart_regimens#GHSG_HD12|See link]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025897/ Kumar et al. 2016]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |}
@@ Line 2,295: / Line 2,295: @@
 |-
 |[http://jco.ascopubs.org/content/32/12/1188.long Raemaekers et al. 2014 (EORTC/LYSA/FIL H10)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC.2FLYSA.2FFIL_H10|See link]]
 |[[Complex_multipart_regimens#EORTC.2FLYSA.2FFIL_H10|See link]]
@@ Line 2,302: / Line 2,302: @@
 ====Preceding treatment====
 *EORTC H10 F: [[#ABVD|ABVD]] x 3
-*EORTC H10 U:''' [[#ABVD|ABVD]] x 4
+*EORTC H10 U:''' [[#ABVD|ABVD]] x 4'''
 ====Radiotherapy====
 *30 Gy (+ 6 Gy boost)
@@ Line 2,314: / Line 2,314: @@
 |-
 |[http://jco.ascopubs.org/content/25/23/3495.long Engert et al. 2007 (GHSG HD7)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |EFRT
-|style="background-color:#1a9850"|Superior FFTF
+| style="background-color:#1a9850" |Superior FFTF
 |-
 |}
@@ Line 2,332: / Line 2,332: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932020/ Meyer et al. 2011 (NCIC CTG/ECOG HD.6)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#NCIC_CTG.2FECOG_HD.6|See link]]
 |[[Complex_multipart_regimens#NCIC_CTG.2FECOG_HD.6|See link]]
@@ Line 2,351: / Line 2,351: @@
 |-
 |[http://jco.ascopubs.org/content/22/14/2835.long Bonadonna et al. 2004]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |STNI x 36 Gy
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa064601 Fermé et al. 2007 (EORTC-GELA H8-F)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC-GELA_H8-F|See link]]
 |[[Complex_multipart_regimens#EORTC-GELA_H8-F|See link]]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa064601 Fermé et al. 2007 (EORTC-GELA H8-U)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC-GELA_H8-U|See link]]
 |[[Complex_multipart_regimens#EORTC-GELA_H8-U|See link]]
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451176/ Advani et al. 2015 (ECOG E2496)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |}
@@ Line 2,387: / Line 2,387: @@
 |-
 |[http://jco.ascopubs.org/content/22/14/2835.long Bonadonna et al. 2004]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |IFRT x 36 Gy
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
@@ Line 2,405: / Line 2,405: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa064601 Fermé et al. 2007 (EORTC-GELA H8-U)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC-GELA_H8-U|See link]]
 |[[Complex_multipart_regimens#EORTC-GELA_H8-U|See link]]
@@ Line 2,424: / Line 2,424: @@
 |-
 |[http://jco.ascopubs.org/content/22/14/2835.long Bonadonna et al. 2004]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |STNI x 40 Gy
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa064601 Fermé et al. 2007 (EORTC-GELA H8-F)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC-GELA_H8-F|See link]]
 |[[Complex_multipart_regimens#EORTC-GELA_H8-F|See link]]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa064601 Fermé et al. 2007 (EORTC-GELA H8-U)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[Complex_multipart_regimens#EORTC-GELA_H8-U|See link]]
 |[[Complex_multipart_regimens#EORTC-GELA_H8-U|See link]]
@@ Line 2,454: / Line 2,454: @@
 |-
 |[http://jco.ascopubs.org/content/22/14/2835.long Bonadonna et al. 2004]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |IFRT x 40 Gy
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
@@ Line 2,506: / Line 2,506: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1408648 Radford et al. 2015 (UK NCRI RAPID)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
@@ Line 2,538: / Line 2,538: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961236/ Johnson et al. 2016 (RATHL)]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
 |-
 |}
@@ Line 2,573: / Line 2,573: @@
 |-
 |[http://jco.ascopubs.org/content/34/27/3293.full Santoro et al. 2016]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,605: / Line 2,605: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862960/ Moskowitz et al. 2013]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#9ebcda"|ORR: 53%
+| style="background-color:#9ebcda" |ORR: 53%
 |-
 |}
@@ Line 2,632: / Line 2,632: @@
 ![[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://ash.confex.com/ash/2014/webprogram/Paper67044.html LaCasce et al. 2014]
+|[http://www.bloodjournal.org/content/124/21/293 LaCasce et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,643: / Line 2,643: @@
 ===References===
-#'''Abstract:''' LaCasce A, Bociek RG, Matous J, et al. Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory after Frontline Therapy. Presented at: 2014 ASH Annual Meeting; December 6-9, 2014; San Francisco, CA. Abstract 293 [https://ash.confex.com/ash/2014/webprogram/Paper67044.html link to abstract].
+#'''Abstract:''' LaCasce A, Bociek RG, Matous J, et al. Brentuximab Vedotin in Combination with Bendamustine for Patients with Hodgkin Lymphoma who are Relapsed or Refractory after Frontline Therapy. Presented at: 2014 ASH Annual Meeting; December 6-9, 2014; San Francisco, CA. Abstract 293 [http://www.bloodjournal.org/content/124/21/293 link to abstract].
 ==Brentuximab vedotin monotherapy {{#subobject:c7e71|Regimen=1}}==
@@ Line 2,657: / Line 2,657: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646316/ Younes et al. 2012 (SG035-0003)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731651/ Gopal et al. 2012]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994656/ Bartlett et al. 2014]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,681: / Line 2,681: @@
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70013-6/fulltext Moskowitz et al. 2015]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,720: / Line 2,720: @@
 |-
 |[http://bloodjournal.hematologylibrary.org/content/71/1/117.long Valesquez et al. 1988]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269494/ Sureda et al. 2011]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,743: / Line 2,743: @@
 {| border="1" style="text-align:center;"
-!colspan="3"|Dose modifications
+! colspan="3" |Dose modifications
 |-
-!align="left" | Event
+! align="left" | Event
 !Cytarabine (Cytosar)
 !Cisplatin (Platinol)
 |-
-|align="left" | ANC less than 200/uL
+| align="left" | ANC less than 200/uL
 |1000 mg/m<sup>2</sup> x 2 doses
 |100 mg/m<sup>2</sup>
 |-
-|align="left" | Platelets less than 20 x 10<sup>9</sup>/L
+| align="left" | Platelets less than 20 x 10<sup>9</sup>/L
 |1000 mg/m<sup>2</sup> x 2 doses
 |100 mg/m<sup>2</sup>
 |-
-|align="left" | Sepsis associated with neutropenia
+| align="left" | Sepsis associated with neutropenia
 |500 mg/m<sup>2</sup> x 1 dose
 |100 mg/m<sup>2</sup>
 |-
-|align="left" | Cr 1.5 to 2.0
+| align="left" | Cr 1.5 to 2.0
 | -
 |75 mg/m<sup>2</sup>
 |-
-|align="left" | Cr 2.1-3.0
+| align="left" | Cr 2.1-3.0
 | -
 |50 mg/m<sup>2</sup>
@@ Line 2,787: / Line 2,787: @@
 |-
 |[http://annonc.oxfordjournals.org/content/13/10/1628.long Josting et al. 2002]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,820: / Line 2,820: @@
 |-
 |[http://jco.ascopubs.org/content/32/12/1188.long Raemaekers et al. 2014 (EORTC/LYSA/FIL H10)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
@@ Line 2,846: / Line 2,846: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961236/ Johnson et al. 2016 (RATHL)]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
 |-
 |}
@@ Line 2,874: / Line 2,874: @@
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30103-1/fulltext Borchmann et al. 2017 (GHSG HD18)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
@@ Line 2,899: / Line 2,899: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4966513/ Press et al. 2016 (SWOG S0816)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
-|style="background-color:#d3d3d3"|
+| style="background-color:#d3d3d3" |
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30103-1/fulltext Borchmann et al. 2017 (GHSG HD18)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |R-BEACOPP<sub>escalated</sub>
-|style="background-color:#ffffbf"|Seems not superior
+| style="background-color:#ffffbf" |Seems not superior
 |-
 |}
@@ Line 2,945: / Line 2,945: @@
 |-
 |[http://annonc.oxfordjournals.org/content/10/5/593.long Aparicio et al. 1999]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 2,979: / Line 2,979: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420736/ Johnston et al. 2010]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,006: / Line 3,006: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018339/ Gopal et al. 2010]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,042: / Line 3,042: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018339/ Gopal et al. 2010]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,079: / Line 3,079: @@
 |-
 |[http://jco.ascopubs.org/content/18/13/2615.long Santoro et al. 2000]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,104: / Line 3,104: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1002/cncr.23237/full Oki et al. 2007]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,141: / Line 3,141: @@
 |-
 |[http://annonc.oxfordjournals.org/content/18/6/1071.long Bartlett et al. 2007 (CALGB 59804)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,204: / Line 3,204: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pubmed/23763798 Naqi et al. 2013]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,230: / Line 3,230: @@
 |-
 |[http://bloodjournal.hematologylibrary.org/content/97/3/616.long Moskowitz et al. 2001]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,251: / Line 3,251: @@
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70013-6/fulltext Moskowitz et al. 2015]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,285: / Line 3,285: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2141.1998.00989.x/full Bonfante et al. 1998]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,315: / Line 3,315: @@
 |-
 |[http://www.haematologica.org/content/92/1/35.long Santoro et al. 2007]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |[http://jco.ascopubs.org/content/34/12/1376.full Zinzani et al. 2016 (HD0801)]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
 |-
 |}
@@ Line 3,354: / Line 3,354: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217400/ Fehniger et al. 2011]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,380: / Line 3,380: @@
 |-
 |[http://annonc.oxfordjournals.org/content/6/6/609.long Rodriguez et al. 1995]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,408: / Line 3,408: @@
 |-
 |[http://www.haematologica.org/content/84/11/1007.long Fernández-Jiménez et al. 1999]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,425: / Line 3,425: @@
 |-
 |[http://jco.ascopubs.org/content/13/2/396.long Colwill et al. 1995]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,459: / Line 3,459: @@
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30167-X/fulltext Younes et al. 2016]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,473: / Line 3,473: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348009/ Ansell et al. 2014]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
 |-
 |}
@@ Line 3,498: / Line 3,498: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1111/bjh.14133/abstract Martínez et al. 2016 (GELTAMO)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,530: / Line 3,530: @@
 |-
 |[http://jco.ascopubs.org/content/30/18/2197.long Younes et al. 2012]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |Investigator assessment: 27% <br>Central review: 22%
 |Progressed after auto HSCT and had a median of 4 prior systemic regimens (range 2 to 7)
@@ Line 3,557: / Line 3,557: @@
 |-
 |[http://ascopubs.org/doi/full/10.1200/JCO.2016.72.1316 Chen et al. 2017 (KEYNOTE-087)]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
-|style="background-color:#bfd3e6"|ORR: 69%
+| style="background-color:#bfd3e6" |ORR: 69%
 |-
 |}
@@ Line 3,582: / Line 3,582: @@
 |-
 |[http://onlinelibrary.wiley.com/doi/10.1002/cncr.11511/full Younes et al. 2003]
-|style="background-color:#91cf61"|Pilot, >20 pts
+| style="background-color:#91cf61" |Pilot, >20 pts
 |-
 |}
@@ Line 3,607: / Line 3,607: @@
 |-
 |[http://meetinglibrary.asco.org/content/130109-144 Janku et al. 2014]
-|style="background-color:#91cf61"|Non-randomized
+| style="background-color:#91cf61" |Non-randomized
 |-
 |}
@@ Line 3,635: / Line 3,635: @@
 |-
 |[http://jco.ascopubs.org/content/16/2/584.long Little et al. 1998]
-|style="background-color:#ffffbe"|Retrospective
+| style="background-color:#ffffbe" |Retrospective
 |-
 |}
@@ Line 3,659: / Line 3,659: @@
 |-
 |[http://annonc.oxfordjournals.org/content/5/9/817.long Devizzi et al. 1994]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,676: / Line 3,676: @@
 ===Regimen #1 {{#subobject:34d7ea|Variant=1}}===
-''To be completed.
+''To be completed. ''
 ====Preceding treatment====
 *[[#Brentuximab_vedotin_monotherapy_2|Salvage brentuximab vedotin]]
@@ Line 3,686: / Line 3,686: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269494/ Sureda et al. 2011]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,710: / Line 3,710: @@
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238917/ Anderlini et al. 2008]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,731: / Line 3,731: @@
 |-
 |[http://informahealthcare.com/doi/full/10.3109/10428194.2013.838233 Sobol et al. 2013]
-|style="background-color:#91cf61"|Phase II
+| style="background-color:#91cf61" |Phase II
 |-
 |}
@@ Line 3,768: / Line 3,768: @@
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60165-9/fulltext Moskowitz et al. 2015 (AETHERA)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#Observation_2|Placebo]]
-|style="background-color:#1a9850"|Superior PFS
+| style="background-color:#1a9850" |Superior PFS
 |-
 |}
@@ Line 3,798: / Line 3,798: @@
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60165-9/fulltext Moskowitz et al. 2015 (AETHERA)]
-|style="background-color:#1a9851"|Phase III
+| style="background-color:#1a9851" |Phase III
 |[[#Brentuximab_vedotin_monotherapy_3|Brentuximab vedotin]]
-|style="background-color:#d73027"|Inferior PFS
+| style="background-color:#d73027" |Inferior PFS
 |-
 |}
@@ Line 3,821: / Line 3,821: @@
 |-
 |[http://jco.ascopubs.org/content/32/12/1188.long Raemaekers et al. 2014 (EORTC/LYSA/FIL H10)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
@@ Line 3,836: / Line 3,836: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1408648 Radford et al. 2015 (UK NCRI RAPID)]
-|style="background-color:#91cf61"|Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}

Difference between revisions of "Classical Hodgkin lymphoma"

Revision as of 19:51, 12 February 2018

Guidelines

ESMO

NCCN

Untreated, early-stage favorable (ESF)

ABVD

Example orders

Regimen #1, 2 cycles

Chemotherapy

Subsequent treatment

Regimen #2, 2 cycles with response adaptation

Chemotherapy

Subsequent treatment

Regimen #3, 3 cycles with response adaptation

Chemotherapy

Subsequent treatment

Regimen #4, 4 cycles

Chemotherapy

Subsequent treatment

References

AVD

Regimen

Chemotherapy

Subsequent treatment

References

MOPP-ABV

Regimen

Chemotherapy

Subsequent treatment

References

Radiation therapy

Regimen #1, 35 Gy of subtotal nodal irradiation (STNI)

Radiotherapy

Regimen #2, 36 Gy of STNI + 4 Gy boost

Radiotherapy

References

Stanford V

Regimen

Chemotherapy

Subsequent treatment

References

Untreated, early-stage unfavorable (ESU)

ABVD

Example orders

Regimen #1, 2 cycles

Preceding treatment

Chemotherapy

Subsequent treatment

Regimen #2, 2 cycles with response adaptation

Chemotherapy

Subsequent treatment

Regimen #3, 4 cycles

Chemotherapy

Subsequent treatment

Regimen #4, 6 to 8 cycles

Chemotherapy

Subsequent treatment

References

A+AVD

Regimen

Chemotherapy

References

BEACOPP

Example orders

Regimen

Chemotherapy

Subsequent treatment

References

Escalated BEACOPP

Regimen

Chemotherapy

Supportive medications

Subsequent treatment

References

MOPP-ABV

Regimen #1, 4 cycles

Chemotherapy

Subsequent treatment

Regimen #2, 6 cycles

Regimen #3, 8 cycles (ABVD₈)