Classical Hodgkin lymphoma - historical

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

30 regimens on this page 37 variants on this page

Untreated

ABVDm

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

Regimen

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

Chemotherapy

• Doxorubicin (Adriamycin)
• Bleomycin (Blenoxane)
• Vinblastine (Velban)
• Dacarbazine (DTIC)
• Methylprednisolone (Solumedrol)

References

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

ABVE-PC (POG P9425)

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

Regimen variant #2, 3 cycles with response adaptation

Study	Evidence
Schwartz et al. 2009 (POG P9425)	Phase 2

This regimen is intended for pediatric patients, younger than 22 years old. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.

Chemotherapy

• Doxorubicin (Adriamycin) 30 mg/m² IV once per day on days 0 & 1
• Bleomycin (Blenoxane) 10 units/m² IV or SC 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 IV or SC 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 variant #4, 5 cycles

Study	Evidence
Schwartz et al. 2009 (POG P9425)	Phase 2

This regimen is intended for pediatric patients, younger than 22 years old, who are slow early responders. Note that first day of chemotherapy is day 0. Bleomycin and prednisone dosing is post-amendment.

Preceding treatment

• ABVE-PC x 3, with slow early response

Chemotherapy

• Doxorubicin (Adriamycin) 30 mg/m² IV once per day on days 0 & 1
• Bleomycin (Blenoxane) 10 units/m² IV or SC 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 IV or SC once per day from day 5 until neutrophil recovery (held on day 7)

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

Subsequent treatment

• IFRT consolidation x 21 Gy

References

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

BCVPP

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

Regimen

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

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

Chemotherapy

• Carmustine (BCNU)
• Cyclophosphamide (Cytoxan)
• Vincristine (Oncovin)
• Procarbazine (Matulane)
• Prednisone (Sterapred)

References

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

ChlVPP/PABIOE

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

Protocol

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

Chemotherapy, ChlVPP portion

• Chlorambucil (Leukeran)
• Vinblastine (Velban)
• Procarbazine (Matulane)
• Prednisolone (Millipred)

Chemotherapy, PABIOE portion

• Prednisolone (Millipred)
• Doxorubicin (Adriamycin)
• Bleomycin (Blenoxane)
• Vincristine (Oncovin)
• Etoposide (Vepesid)

References

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

COMP

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

Regimen

Study	Evidence
Moxley et al. 1967	Pilot

Chemotherapy

• Cyclophosphamide (Cytoxan)
• Vincristine (Oncovin)
• Methotrexate (MTX)
• Prednisone (Sterapred)

References

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

COPP (CCNU)

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

Regimen

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

Chemotherapy

• Lomustine (CCNU)
• Vincristine (Oncovin)
• Procarbazine (Matulane)
• Prednisone (Sterapred)

References

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

COPP/ABVD

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

Protocol variant #1, 4 cycles

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

Chemotherapy, COPP portion

• Cyclophosphamide (Cytoxan)
• Vincristine (Oncovin)
• Procarbazine (Matulane)
• Prednisone (Sterapred)

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

Chemotherapy, ABVD portion

• Doxorubicin (Adriamycin)
• Bleomycin (Blenoxane)
• Vinblastine (Velban)
• Dacarbazine (DTIC)

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

Subsequent treatment

• GHSG HD5 & HD6: EFRT
• GHSG HD8: EFRT versus IFRT

Protocol variant #2, 6 cycles

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

Chemotherapy, COPP portion

• Cyclophosphamide (Cytoxan)
• Vincristine (Oncovin)
• Procarbazine (Matulane)
• Prednisone (Sterapred)

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

Chemotherapy, ABVD portion

• Doxorubicin (Adriamycin)
• Bleomycin (Blenoxane)
• Vinblastine (Velban)
• Dacarbazine (DTIC)

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

Subsequent treatment

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

Protocol variant #3, 10 cycles

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

Chemotherapy, COPP portion

• Cyclophosphamide (Cytoxan) 500 mg/m² IV once per day on days 1 & 8
• Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once per day on days 1 & 8
• Procarbazine (Matulane) 100 mg/m² (maximum dose of 150 mg) PO once per day on days 1 to 14
• Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 3, 8 to 10

28-day cycle for 5 total cycles of COPP, alternating with 5 total cycles of ABVD

Chemotherapy, ABVD portion

• Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
• Bleomycin (Blenoxane) 9 mg/m² (maximum dose of 15 mg) IV once per day on days 1 & 15
• Vinblastine (Velban) 6 mg/m² (maximum dose of 10 mg) IV once per day on days 1 & 15
• Dacarbazine (DTIC) 250 mg/m² IV once per day on days 1 & 15

28-day cycle for 5 total cycles of ABVD, alternating with 5 total cycles of COPP

Subsequent treatment

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

Dose modifications

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

References

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

CVPP

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

Regimen

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

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

Chemotherapy

• Lomustine (CCNU)
• Vinblastine (Velban)
• Procarbazine (Matulane)
• Prednisone (Sterapred)

References

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

Doxorubicin & Vinblastine

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Regimen

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

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

Chemotherapy

• 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

28-day cycle for 3 cycles

Subsequent treatment

• STLI

References

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

LOPP

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

Regimen

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

Chemotherapy

• Chlorambucil (Leukeran)
• Vincristine (Oncovin)
• Procarbazine (Matulane)
• Prednisone (Sterapred)

References

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

LOPP/EVAP

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

Protocol

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

Chemotherapy, LOPP portion

• Chlorambucil (Leukeran)
• Vincristine (Oncovin)
• Procarbazine (Matulane)
• Prednisone (Sterapred)

Chemotherapy, EVAP portion

• Etoposide (Vepesid)
• Vinblastine (Velban)
• Doxorubicin (Adriamycin)
• Prednisone (Sterapred)

References

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

Mechlorethamine monotherapy

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Regimen

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

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

Chemotherapy

• Mechlorethamine (Mustargen)

References

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

MOPP/ABVD

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

Protocol

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

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

Chemotherapy, MOPP portion

• Mechlorethamine (Mustargen)
• Vincristine (Oncovin)
• Procarbazine (Matulane)
• Prednisone (Sterapred)

Chemotherapy, ABVD portion

• Doxorubicin (Adriamycin)
• Bleomycin (Blenoxane)
• Vinblastine (Velban)
• Dacarbazine (DTIC)

References

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

MVPP

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MVPP: Mechlorethamine, Vinblastine, Procarbazine, Prednisone

Regimen

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

Chemotherapy

• Mechlorethamine (Mustargen)
• Vinblastine (Velban)
• Procarbazine (Matulane)
• Prednisone (Sterapred)

References

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

NOVP

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

Regimen

Study	Evidence
Hagemeister et al. 1990	Phase 2

Chemotherapy

• Mitoxantrone (Novantrone)
• Vincristine (Oncovin)
• Vinblastine (Velban)
• Prednisone (Sterapred)

References

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

SCAB

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

Regimen

Study	Evidence
Diggs et al. 1981	Non-randomized

Chemotherapy

• Streptozocin (Zanosar)
• Lomustine (CCNU)
• Doxorubicin (Adriamycin)
• Bleomycin (Blenoxane)

References

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

Vinblastine monotherapy

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Regimen

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

Chemotherapy

• Vinblastine (Velban)

References

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

OPPA

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

Regimen

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

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

Chemotherapy

• 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

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

VAMP (Methotrexate)

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

Regimen

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

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

Chemotherapy

• Vinblastine (Velban)
• Doxorubicin (Adriamycin)
• Methotrexate (MTX)
• Prednisone (Sterapred)

4 cycles

Subsequent treatment

• Early responders: Observation versus RT

References

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

ABVE

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

Regimen

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

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

Chemotherapy

• 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
• Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV once per day on days 1 & 15
• Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 5

Supportive medications

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

28-day cycle for 2 cycles

Subsequent treatment

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

References

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

MOPP

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

Regimen variant #3, uncapped vincristine

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

Chemotherapy

• 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

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

Consolidation after upfront therapy

C-MOPP

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

Regimen variant #1, 2 cycles

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

Preceding treatment

• 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 variant #2, 4 cycles

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

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

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

COPDAC

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

Regimen variant #1, 2 cycles

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

Preceding treatment

• 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 variant #2, 4 cycles

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

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

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

Maintenance after upfront therapy

Bacillus Calmette-Guérin (BCG) monotherapy

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Regimen

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

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

Immunotherapy

• Bacillus Calmette-Guérin (BCG)

References

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

Relapsed or refractory, salvage therapy

ABDIC

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

Regimen

Study	Evidence
Rodgers et al. 1980	Phase 2

Chemotherapy

• Doxorubicin (Adriamycin)
• Bleomycin (Blenoxane)
• Dacarbazine (DTIC)
• Lomustine (CCNU)
• Prednisone (Sterapred)

References

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

ABVD

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

Regimen

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

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

Chemotherapy

• Doxorubicin (Adriamycin)
• Bleomycin (Blenoxane)
• Vinblastine (Velban)
• Dacarbazine (DTIC)

References

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

B-CAVe

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

Regimen

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

Chemotherapy

• Bleomycin (Blenoxane)
• Lomustine (CCNU)
• Doxorubicin (Adriamycin)
• Vinblastine (Velban)

References

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

BVCPP

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

Regimen

Study	Evidence
Durant et al. 1978	Non-randomized

Chemotherapy

• Carmustine (BCNU)
• Vinblastine (Velban)
• Cyclophosphamide (Cytoxan)
• Procarbazine (Matulane)
• Prednisone (Sterapred)

Subsequent treatment

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

References

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

BVDS

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BVDS: Bleomycin, Vinblastine, Doxorubicin, Streptozocin

Regimen

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

Chemotherapy

• Bleomycin (Blenoxane)
• Vinblastine (Velban)
• Doxorubicin (Adriamycin)
• Streptozocin (Zanosar)

References

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

CEP

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CEP: CCNU (Lomustine), Etoposide, Prednimustine

Regimen

Study	Evidence
Santoro et al. 1986	Non-randomized

Chemotherapy

• Lomustine (CCNU)
• Etoposide (Vepesid)
• Prednimustine (Stereocyt)

References

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

CVB

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CVB: CCNU (Lomustine), Vinblastine, Bleomycin

Regimen

Study	Evidence
Goldman & Dawson 1975	Non-randomized

Chemotherapy

• Lomustine (CCNU)
• Vinblastine (Velban)
• Bleomycin (Blenoxane)

References

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

CVPP

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

Regimen

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

Chemotherapy

• Lomustine (CCNU)
• Vinblastine (Velban)
• Procarbazine (Matulane)
• Prednisone (Sterapred)

References

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

SCAB

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

Regimen

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

Chemotherapy

• Streptozocin (Zanosar)
• Lomustine (CCNU)
• Doxorubicin (Adriamycin)
• Bleomycin (Blenoxane)

References

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

Relapsed or refractory, further lines of therapy

Carmustine monotherapy

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Regimen

Study	Evidence
Young et al. 1971	Non-randomized

Chemotherapy

• Carmustine (BCNU)

References

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

Doxorubicin & Lomustine

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Regimen

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

Chemotherapy

• Doxorubicin (Adriamycin)
• Lomustine (CCNU)

References

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

Sirolimus & Vorinostat

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Regimen

Study	Evidence
Janku et al. 2020 (MDACC 2009-0729)	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.

Targeted therapy

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

28-day cycles

References

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