Classical Hodgkin lymphoma - historical

The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main cHL page for current regimens.

30 regimens on this page 37 variants on this page

Untreated

ABVDm

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

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Le Maignan et al. 2003 (H90-NM)	1990-1996	Phase 3 (C)	EBVMm	Did not meet primary endpoint of OS

Note: the manuscript states that the drugs were given on days 1 & 14, which is clearly incorrect.

Chemotherapy

• Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
• Bleomycin (Blenoxane) 10 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

Glucocorticoid therapy

• Methylprednisolone (Solumedrol) 120 mg/m² IV once per day on days 1 & 15

28-day cycle for 3 cycles

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 contains dosing details in manuscript PubMed

COMP

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

Regimen

Study	Evidence
Moxley et al. 1967	Pilot

Chemotherapy

• Cyclophosphamide (Cytoxan) 600 mg/m² IV once per day on days 1 & 8
• Vincristine (Oncovin) 1.2 mg/m² IV once per day on days 1 & 8
• Methotrexate (MTX) 30 mg/m² IM once per day on days 1, 4, 8, 11

Glucocorticoid therapy

• Prednisone (Sterapred) 60 mg/m² PO once per day on days 1 to 14

21-day cycle for 3 cycles

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 contains dosing details in manuscript PubMed

COPP/ABVD

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

Regimen variant #1, 4 cycles

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sieber et al. 2002 (GHSG HD5)	1988-1993	Phase 3 (C)	COPP/ABV/IMEP	Did not meet co-primary endpoint of OS
Sieber et al. 2004 (GHSG HD6)	1988-1993	Phase 3 (C)	COPP/ABV/IMEP	Did not meet primary endpoint of FFTF
Engert et al. 2003 (GHSG HD8)	1993-1998	Non-randomized part of RCT

Chemotherapy, COPP portion (cycles 1 & 3)

• Cyclophosphamide (Cytoxan) 650 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 PO once per day on days 1 to 14

Glucocorticoid therapy, COPP portion (cycles 1 & 3)

• Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

Chemotherapy, ABVD portion (cycles 2 & 4)

• Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
• Bleomycin (Blenoxane) 10 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

Subsequent treatment

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

Regimen variant #2, 6 cycles

Study	Dates of enrollment	Evidence
Diehl et al. 1995 (GHSG HD3)	1984-01 to 1988-02	Non-randomized part of RCT

Chemotherapy, COPP portion (cycles 1, 3, 5)

• Cyclophosphamide (Cytoxan) 650 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 PO once per day on days 1 to 14

Glucocorticoid therapy, COPP portion (cycles 1, 3, 5)

• Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

Chemotherapy, ABVD portion (cycles 2, 4, 6)

• Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 15
• Bleomycin (Blenoxane) 10 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 6 cycles

Subsequent treatment

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

Regimen variant #3, 10 cycles

Study	Dates 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	Did not meet co-primary endpoint of OS

Chemotherapy, COPP portion (cycles 1, 3, 5, 7, 9)

• 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

Glucocorticoid therapy, COPP portion (cycles 1, 3, 5, 7, 9)

• Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 3, 8 to 10

Chemotherapy, ABVD portion (cycles 2, 4, 6, 8, 10)

• 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 10 cycles

Subsequent treatment

• JCOG 8905 & GHSG HD9, patients with bulky (at least 10 cm maximum diameter) disease: IFRT x 3000 cGy consolidation
• GHSG HD9elderly, initial bulky disease (single lymph node involvement or a conglomerate mass of at least 5 cm in any diameter): IFRT x 3000 cGy consolidation
• GHSG HD9elderly, residual tumor after chemotherapy: IFRT x 4000 cGy consolidation

Dose and schedule modifications

• Treatment was postponed for at least 1 week or until recovery if:
  • Pretreatment ANC was less than 1500/μL
  • 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 contains dosing details in manuscript PubMed
2. GHSG HD9: Diehl V, Franklin J, Hasenclever D, Tesch H, Pfreundschuh M, Lathan B, Paulus U, Sieber M, Rueffer JU, Sextro M, Engert A, Wolf J, Hermann R, Holmer L, Stappert-Jahn U, Winnerlein-Trump E, Wulf G, Krause S, Glunz A, von Kalle K, Bischoff H, Haedicke C, Duehmke E, Georgii A, Loeffler M. BEACOPP, a new dose-escalated and accelerated regimen, is at least as effective as COPP/ABVD in patients with advanced-stage Hodgkin's lymphoma: interim report from a trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 1998 Dec;16(12):3810-21. link to original articlecontains dosing details in manuscript PubMed
   1. Update: Diehl V, Franklin J, Pfreundschuh M, Lathan B, Paulus U, Hasenclever D, Tesch H, Herrmann R, Dörken B, Müller-Hermelink HK, Dühmke E, Loeffler M; German Hodgkin's Lymphoma Study Group. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12;348(24):2386-95. link to original articlecontains dosing details in abstract PubMed
   2. Update: Engert A, Diehl V, Franklin J, Lohri A, Dörken B, Ludwig WD, Koch P, Hänel M, Pfreundschuh M, Wilhelm M, Trümper L, Aulitzky WE, Bentz M, Rummel M, Sezer O, Müller-Hermelink HK, Hasenclever D, Löffler M. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. 2009 Sep 20;27(27):4548-54. Epub 2009 Aug 24. link to original article PubMed
   3. Pooled update: von Tresckow B, Kreissl S, Dipl-Math HG, Bröckelmann PJ, Pabst T, Fridrik M, Rummel M, Jung W, Thiemer J, Sasse S, Bürkle C, Baues C, Diehl V, Engert A, Borchmann P; German Hodgkin Study Group. Intensive treatment strategies in advanced-stage Hodgkin's lymphoma (HD9 and HD12): analysis of long-term survival in two randomised trials. Lancet Haematol. 2018 Oct 01;5(10):e462-73. link to original article PubMed
3. JCOG 8905: Takenaka T, Mikuni C, Miura A, Sasaki T, Suzuki H, Hotta T, Hirano M, Fukuhara S, Sugiyama H, Nasu K, Dohi H, Kozuru M, Tomonaga M, Tajima K, Niimi M, Fukuda H, Mukai K, Shimoyama M; Lymphoma Study Group of the Japan Clinical Oncology Group. Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). Jpn J Clin Oncol. 2000 Mar;30(3):146-52. link to original article contains dosing details in abstract PubMed
4. GHSG HD5: Sieber M, Tesch H, Pfistner B, Rueffer U, Lathan B, Brosteanu O, Paulus U, Koch T, Pfreundschuh M, Loeffler M, Engert A, Josting A, Wolf J, Hasenclever D, Franklin J, Duehmke E, Georgii A, Schalk KP, Kirchner H, Doelken G, Munker R, Koch P, Herrmann R, Greil R, Anselmo AP, Diehl V. Rapidly alternating COPP/ABV/IMEP is not superior to conventional alternating COPP/ABVD in combination with extended-field radiotherapy in intermediate-stage Hodgkin's lymphoma: final results of the German Hodgkin's Lymphoma Study Group Trial HD5. J Clin Oncol. 2002 Jan 15;20(2):476-84. link to original article contains dosing details in manuscript PubMed
5. GHSG HD8: Engert A, Schiller P, Josting A, Herrmann R, Koch P, Sieber M, Boissevain F, De Wit M, Mezger J, Duhmke E, Willich N, Muller RP, Schmidt BF, Renner H, Muller-Hermelink HK, Pfistner B, Wolf J, Hasenclever D, Loffler M, Diehl V; German Hodgkin's Lymphoma Study Group. Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2003 Oct 1;21(19):3601-8. Epub 2003 Aug 11. link to original article contains dosing details in abstract PubMed
   1. Update: Sasse S, Klimm B, Görgen H, Fuchs M, Heyden-Honerkamp A, Lohri A, Koch O, Wilhelm M, Trenn G, Finke J, Müller RP, Diehl V, Eich HT, Borchmann P, Engert A; German Hodgkin Study Group (GHSG). Comparing long-term toxicity and efficacy of combined modality treatment including extended- or involved-field radiotherapy in early-stage Hodgkin's lymphoma. Ann Oncol. 2012 Nov;23(11):2953-9. Epub 2012 Jul 5. link to original article PubMed
   2. Update: Sasse S, Bröckelmann PJ, Goergen H, Plütschow A, Müller H, Kreissl S, Buerkle C, Borchmann S, Fuchs M, Borchmann P, Diehl V, Engert A. Long-term follow-up of contemporary treatment in early-stage Hodgkin lymphoma: updated analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 trials. J Clin Oncol. 2017 Jun 20;35(18):1999-2007. Epub 2017 Apr 18. link to original article PubMed
6. GHSG HD6: Sieber M, Tesch H, Pfistner B, Rueffer U, Paulus U, Munker R, Hermann R, Doelken G, Koch P, Oertel J, Roller S, Worst P, Bischof H, Glunz A, Greil R, von Kalle K, Schalk KP, Hasenclever D, Brosteanu O, Duehmke E, Georgii A, Engert A, Loeffler M, Diehl V, Mueller RP, Willich N, Fischer R, Hansmann ML, Stein H, Schober T, Koch B; German Hodgkin's Lymphoma Study Group. Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial. Ann Oncol. 2004 Feb;15(2):276-82. link to original article PubMed
7. GHSG HD9elderly: Ballova V, Rüffer JU, Haverkamp H, Pfistner B, Müller-Hermelink HK, Dühmke E, Worst P, Wilhelmy M, Naumann R, Hentrich M, Eich HT, Josting A, Löffler M, Diehl V, Engert A. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005 Jan;16(1):124-31. link to original articlecontains dosing details in abstract PubMed

CVPP (Cyclophosphamide)

CVPP: Cyclophosphamide, Vinblastine, Procarbazine, Prednisone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
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

• Cyclophosphamide (Cytoxan) 600 mg/m² IV once per day on days 1 & 8
• Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 8
• Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 14

Glucocorticoid therapy

• Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14

1-month cycle for 6 cycles

References

1. 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
2. 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
3. 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 contains dosing details in manuscript PubMed

Doxorubicin & Vinblastine

Regimen

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

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 consolidation

References

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

Mechlorethamine monotherapy

Regimen

Study	Dates 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	Did not meet primary endpoint of ORR

Note: 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

NOVP

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

Regimen

Study	Dates of enrollment	Evidence
Hagemeister et al. 1990	1988-06 to 1989-12	Phase 2

Note: The original manuscript is not available online; a physical copy was reviewed and does not contain dosing details.

Chemotherapy

• Mitoxantrone (Novantrone) dose not specified
• Vincristine (Oncovin) dose not specified
• Vinblastine (Velban) dose not specified

Glucocorticoid therapy

• Prednisone (Sterapred) dose not specified

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. does not contain dosing details in manuscript PubMed

Vinblastine monotherapy

Regimen

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

Chemotherapy

• Vinblastine (Velban) 0.15 mg/kg IV once on day 1

7-day cycles

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 contains dosing details in manuscript PubMed

Untreated, advanced stage

BCVPP

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

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Durant et al. 1978	1971-1975	Non-randomized part of RCT
Bakemeier et al. 1984	1972-1976	Phase 3 (E-esc)	MOPP	Did not meet endpoint of CR rate1

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

Chemotherapy

• Carmustine (BCNU) 100 mg/m² IV once on day 1
• Cyclophosphamide (Cytoxan) 600 mg/m² IV once on day 1
• Vinblastine (Velban) 5 mg/m² IV once on day 1
• Procarbazine (Matulane) 50 mg/m² PO twice per day on days 1 to 10

Glucocorticoid therapy

• Prednisone (Sterapred) 60 mg/m²/day PO on days 1 to 10

28-day cycle for 6 cycles

Subsequent treatment

• Durant et al. 1978, responders: No further therapy vs BCVPP continuation x 6 vs MOPP x 6

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 contains dosing details in manuscript PubMed
2. Bakemeier RF, Anderson JR, Costello W, Rosner G, Horton J, Glick JH, Hines JD, Berard CW, DeVita VT Jr; ECOG. BCVPP chemotherapy for advanced Hodgkin's disease: evidence for greater duration of complete remission, greater survival, and less toxicity than with a MOPP regimen: results of the Eastern Cooperative Oncology Group study. Ann Intern Med. 1984 Oct;101(4):447-56. link to original article PubMed

ChlVPP/PABIOE

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

Regimen

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

Chemotherapy, ChlVPP portion (cycles 1, 3, 5, 7)

• Chlorambucil (Leukeran) 6 mg/m² (maximum dose of 10 mg) PO once per day on days 1 to 14
• Vinblastine (Velban) 6 mg/m² (maximum dose of 10 mg) IV once per day on days 1 & 8
• Procarbazine (Matulane) 100 mg/m² (maximum dose of 200 mg) PO once per day on days 1 to 14

Glucocorticoid therapy, ChlVPP portion (cycles 1, 3, 5, 7)

• Prednisolone (Millipred) 40 mg/m² (maximum dose of 60 mg) PO once per day on days 1 to 14

Glucocorticoid therapy, PABIOE portion (cycles 2, 4, 6, 8)

• Prednisolone (Millipred) 40 mg/m² (maximum dose of 60 mg) PO once per day on days 1 to 10

Chemotherapy, PABIOE portion (cycles 2, 4, 6, 8)

• Doxorubicin (Adriamycin) 40 mg/m² IV once on day 1
• Bleomycin (Blenoxane) 10 units/m² (route not specified) 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
• Etoposide (Vepesid) 200 mg/m² PO once per day on days 1 to 3

28-day cycle alternating with 21-day cycle for 8 cycles (ChlVPP x 4; PABIOE x 4)

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 contains dosing details in manuscript PubMed
2. UKLG LY09: Johnson PW, Radford JA, Cullen MH, Sydes MR, Walewski J, Jack AS, MacLennan KA, Stenning SP, Clawson S, Smith P, Ryder D, Hancock BW; United Kingdom Lymphoma Group. Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol. 2005 Dec 20;23(36):9208-18. Epub 2005 Nov 28. link to original article contains dosing details in manuscript PubMed NCT00003421
   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

COPP (CCNU)

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

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Cooper et al. 1980	1972-1975	Phase 3 (E-switch-ic)	1. CVPP	Did not meet endpoint of OS
			2. MOPP	Did not meet endpoint of OS
			3. MVPP	Did not meet endpoint of OS

Chemotherapy

• Lomustine (CCNU) 75 mg/m² PO once on day 1
• 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

Glucocorticoid therapy

• Prednisone (Sterapred) as follows:
  • Cycles 1, 3, 5: 40 mg/m² PO once per day on days 1 to 14

28-day cycle for 6 cycles

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 contains dosing details in manuscript PubMed

CVPP

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

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Cooper et al. 1980	1972-1975	Phase 3 (E-switch-ic)	1. COPP	Did not meet endpoint of OS
			2. MOPP	Seems to have superior CR rate
			3. MVPP	Did not meet endpoint of OS

Chemotherapy

• Lomustine (CCNU) 75 mg/m² PO once on day 1
• Vinblastine (Velban) 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

Glucocorticoid therapy

• Prednisone (Sterapred) as follows:
  • Cycles 1, 3, 5: 40 mg/m² PO once per day on days 1 to 14

28-day cycle for 6 cycles

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 contains dosing details in manuscript PubMed

LOPP

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

Regimen

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

Chemotherapy

• Chlorambucil (Leukeran) 10 mg PO once per day on days 1 to 10
• 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 200 mg) PO once per day on days 1 to 10

Glucocorticoid therapy

• Prednisone (Sterapred) 25 mg/m² (maximum dose of 60 mg) PO once per day on days 1 to 14

28-day cycle for 8 cycles

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 contains dosing details in manuscript PubMed

LOPP/EVAP

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

Regimen

Study	Dates 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 (cycles 1, 3, 5, 7)

• Chlorambucil (Leukeran) 10 mg PO once per day on days 1 to 10
• 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 200 mg) PO once per day on days 1 to 10

Glucocorticoid therapy, LOPP portion (cycles 1, 3, 5, 7)

• Prednisone (Sterapred) 25 mg/m² (maximum dose of 60 mg) PO once per day on days 1 to 14

Chemotherapy, EVAP portion (cycles 2, 4, 6, 8)

• Etoposide (Vepesid) 150 mg/m² (maximum dose of 200 mg) PO once per day on days 1 to 3
• Vinblastine (Velban) 6 mg/m² (maximum dose of 10 mg) IV once per day on days 1 & 8
• Doxorubicin (Adriamycin) 25 mg/m² IV once per day on days 1 & 8

Glucocorticoid therapy, EVAP portion (cycles 2, 4, 6, 8)

• Prednisone (Sterapred) 25 mg/m² (maximum dose of 60 mg) PO once per day on days 1 to 14

28-day cycle for 8 cycles (LOPP x 4; EVAP x 4)

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 contains dosing details in manuscript 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

MOPP/ABVD

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

Regimen variant #1, 12 cycles, uncapped vincristine

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Santoro et al. 1982	1974-1980	Phase 3 (E-switch-ic)	MOPP	Superior PFS
Viviani et al. 1996	1982-1990	Phase 3 (C)	MOPP-ABVD	Did not meet endpoint of CR rate

Chemotherapy, MOPP portion (cycles 1, 3, 5, 7, 9, 11)

• 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

Glucocorticoid therapy, MOPP portion (cycles 1, 3, 5, 7, 9, 11)

• Prednisone (Sterapred) as follows:
  • Cycles 1 & 7: 40 mg/m² PO once per day on days 1 to 14

Chemotherapy, ABVD portion (cycles 2, 4, 6, 8, 10, 12)

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

28-day cycle for at least 12 cycles

Regimen variant #2, 12 cycles, capped vincristine

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Canellos et al. 1992 (CALGB 8251)	1982-NR	Phase 3 (E-switch-ic)	1. ABVD	Did not meet primary endpoint of CR rate1
			2. MOPP	Seems to have superior EFS1 (secondary endpoint)

¹Reported efficacy for CALGB 8251 is based on the 2009 update.
Note: full dosing details are not available in the manuscript, which stated that the Milan Cancer Institute scheme was used for ABVD dosing.

Chemotherapy, MOPP portion (cycles 1, 3, 5, 7, 9, 11)

• Mechlorethamine (Mustargen) 6 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 PO once per day on days 1 to 14

Glucocorticoid therapy, MOPP portion (cycles 1, 3, 5, 7, 9, 11)

• Prednisone (Sterapred) as follows:
  • Cycles 1 & 7: 40 mg/m² PO once per day on days 1 to 14

Chemotherapy, ABVD portion (cycles 2, 4, 6, 8, 10, 12)

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

28-day cycle for 12 cycles

Regimen variant #3, 12 cycles, capped vincristine, alternate prednisone dosing

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hutchinson et al. 1998 (CCG-521)	1986-1990	Phase 3 (C)	ABVD, then RT	Might have inferior EFS

Chemotherapy, MOPP portion (cycles 1, 3, 5, 7, 9, 11)

• Mechlorethamine (Mustargen) 6 mg/m² IV push once per day on days 1 & 8
• Vincristine (Oncovin) 1.5 mg/m² (maximum dose of 2 mg) IV push once per day on days 1 & 8
• Procarbazine (Matulane) 100 mg/m² PO once per day on days 1 to 14

Glucocorticoid therapy, MOPP portion (cycles 1, 3, 5, 7, 9, 11)

• Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 14, in 3 divided doses per day

Chemotherapy, ABVD portion (cycles 2, 4, 6, 8, 10, 12)

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

28-day cycle for 12 cycles

Regimen variant #4, 8 cycles

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Connor et al. 1997 (NCIC-CTG HD4)	1984-1989	Phase 3 (C)	MOPP-ABV	Did not meet co-primary endpoint of OS

Chemotherapy, MOPP portion (cycles 1, 3, 5, 7)

• Mechlorethamine (Mustargen) 6 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 PO once per day on days 1 to 14

Glucocorticoid therapy, MOPP portion (cycles 1, 3, 5, 7)

• Prednisone (Sterapred) as follows:
  • Cycles 1 & 5: 40 mg/m² PO once per day on days 1 to 14

Chemotherapy, ABVD portion (cycles 2, 4, 6, 8)

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

28-day cycle for 8 cycles

Regimen variant #5, 8 cycles, lower-dose ABVD

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Somers et al. 1994	1981-1986	Phase 3 (E-switch-ic)	MOPP x 8	Seems to have superior FFS

Note: Each portion is given twice before alternating (AABBAABB pattern). ABVD doses are per the "Milan scheme".

Chemotherapy, MOPP portion (cycles 1, 2, 5, 6)

• Mechlorethamine (Mustargen) 6 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 PO once per day on days 1 to 14

Glucocorticoid therapy, MOPP portion (cycles 1, 2, 5, 6)

• Prednisone (Sterapred) 25 mg/m² PO once per day on days 1 to 14

Chemotherapy, ABVD portion (cycles 3, 4, 7, 8)

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

28-day cycle for 8 cycles

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 contains dosing details in manuscript 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 contains partial dosing details in manuscript 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 contains dosing details in manuscript 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 does not contain dosing details 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 contains dosing details in manuscript 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 contains dosing details in manuscript PubMed

MVPP

MVPP: Mechlorethamine, Vinblastine, Procarbazine, Prednisone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Cooper et al. 1980	1972-1975	Phase 3 (E-switch-ic)	1. COPP	Did not meet endpoint of OS
			2. CVPP	Did not meet endpoint of OS
			3. MOPP	Did not meet endpoint of OS

Chemotherapy

• Mechlorethamine (Mustargen) 6 mg/m² IV once per day on days 1 & 8
• Vinblastine (Velban) 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

Glucocorticoid therapy

• Prednisone (Sterapred) as follows:
  • Cycles 1, 3, 5: 40 mg/m² PO once per day on days 1 to 14

28-day cycle for 6 cycles

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 contains dosing details in manuscript PubMed

SCAB

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

Regimen

Study	Dates of enrollment	Evidence
Diggs et al. 1981	1976-1978	Non-randomized

Chemotherapy

• Streptozocin (Zanosar) 500 mg/m² IV once per day on days 1 to 5
• Lomustine (CCNU) 100 mg/m² PO once on day 1
• Doxorubicin (Adriamycin) 45 mg/m² IV once on day 1
• Bleomycin (Blenoxane) 15 mg/m² IM once per day on days 1 to 7

1-month cycles

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 contains dosing details in manuscript 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

VEBEP

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

Regimen

Study	Dates of enrollment	Evidence
Viviani et al. 1999	1990-09 to 1993-03	Phase 2

Note: The full manuscript is not available online for review.

Chemotherapy

• Etoposide (Vepesid)
• Epirubicin (Ellence)
• Bleomycin (Blenoxane)
• Cyclophosphamide (Cytoxan)

Glucocorticoid therapy

• Prednisolone (Millipred)

References

1. 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 does not contain dosing details in abstract

Maintenance after upfront therapy

BCG vaccine monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sokal et al. 1974	1965-1967	Randomized, fewer than 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

• BCG vaccine

References

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

Relapsed or refractory, salvage therapy

ABDIC

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

Regimen

Study	Dates of enrollment	Evidence
Rodgers et al. 1980	1974-1978	Phase 2

Chemotherapy

• Doxorubicin (Adriamycin) 45 mg/m² IV once on day 1
• Bleomycin (Blenoxane) 5 mg/m² IV once per day on days 1 & 5
• Dacarbazine (DTIC) 200 mg/m² IV once per day on days 1 to 5
• Lomustine (CCNU) 50 mg/m² PO once on day 1

Glucocorticoid therapy

• Prednisone (Sterapred) 40 mg/m² PO once per day on days 1 to 5

28-day cycles

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 contains dosing details in manuscript PubMed
   1. Update: Tannir N, Hagemeister F, Velasquez W, Cabanillas F. Long-term follow-up with ABDIC salvage chemotherapy of MOPP-resistant Hodgkin's disease. J Clin Oncol. 1983 Jul;1(7):432-9. link to original article PubMed

ABVD

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

Regimen

Study	Dates of enrollment	Evidence
Harker et al. 1984	1973-1982	Non-randomized
Krikorian et al. 1978	1975-06-19 to 1976-12-22	Phase 2
Santoro & Bonadonna 1979	NR	Non-randomized
Santoro et al. 1982a	NR in abstract	Non-randomized

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

Chemotherapy

• Doxorubicin (Adriamycin) 25 mg/m² IV once on day 1
• Bleomycin (Blenoxane) 10 mg/m² IV once on day 1
• Vinblastine (Velban) 6 mg/m² IV once on day 1
• Dacarbazine (DTIC) 375 mg/m² IV once on day 1

14-day cycles

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

B-CAVe

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

Regimen

Study	Dates of enrollment	Evidence
Porzig et al. 1978	1973-1976	Non-randomized
Harker et al. 1984	1973-1982	Non-randomized

Chemotherapy

• Bleomycin (Blenoxane) 2.5 mg/m² IV once per day on days 1, 28, 35
• Lomustine (CCNU) 100 mg/m² PO once on day 1
• Doxorubicin (Adriamycin) 60 mg/m² IV once on day 1
• Vinblastine (Velban) 5 mg/m² IV once on day 1

42-day cycles

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 contains dosing details in manuscript PubMed
2. Harker WG, Kushlan P, Rosenberg SA. Combination chemotherapy for advanced Hodgkin's disease after failure of MOPP: ABVD and B-CAVe. Ann Intern Med. 1984 Oct;101(4):440-6. link to original article PubMed

BVCPP

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

Regimen

Study	Dates of enrollment	Evidence
Durant et al. 1978	1971-1975	Non-randomized part of RCT

Chemotherapy

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

Glucocorticoid therapy

• Prednisone (Sterapred)

Subsequent treatment

• Durant et al. 1978, patients who achieved CR: No additional therapy versus MOPP x 6 versus BVCPP continuation x 6 additional cycles

References

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

BVDS

BVDS: Bleomycin, Vinblastine, Doxorubicin, Streptozocin

Regimen

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

Chemotherapy

• Bleomycin (Blenoxane) 5 mg/m² IV once per day on days 1 & 15
• Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 15
• Doxorubicin (Adriamycin) 30 mg/m² IV once on day 1
• Streptozocin (Zanosar) 1500 mg/m² IV once per day on days 1 & 15

1-month cycle for at least 12 cycles

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 contains dosing details in manuscript PubMed

CEP

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

CVB: CCNU (Lomustine), Vinblastine, Bleomycin

Regimen

Study	Dates of enrollment	Evidence
Goldman & Dawson 1975	1973-1975	Non-randomized

Chemotherapy

• Lomustine (CCNU) 100 mg/m² PO once on day 1
• Vinblastine (Velban) 6 mg/m² IV once per day on days 1 & 8
• Bleomycin (Blenoxane) 15 mg IM once per day on days 1 & 8

28-day cycles

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 contains dosing details in manuscript PubMed

CVPP

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

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Vinciguerra et al. 1986	1975-1981	Randomized (C)	1. ABOS 2. CVPP/ABOS	Did not meet co-primary endpoints of CR rate/DFS/OS

Chemotherapy

• Lomustine (CCNU) 75 mg/m² PO once on day 1
• Vinblastine (Velban) 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

Glucocorticoid therapy

• Prednisone (Sterapred) as follows:
  • Cycles 1, 4, 7, 10: 40 mg/m² PO once per day on days 1 to 14

1-month cycle for 12 cycles

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 contains dosing details in manuscript PubMed

SCAB

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

Regimen

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

Chemotherapy

• Streptozocin (Zanosar) 500 mg/m² IV once per day on days 1 to 5
• Lomustine (CCNU) 100 mg/m² PO once on day 1
• Doxorubicin (Adriamycin) 45 mg/m² IV once on day 1
• Bleomycin (Blenoxane) 15 mg/m² IM once per day on days 1 & 8

28-day cycles

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 contains dosing details in abstract PubMed

Relapsed or refractory, further lines of therapy

Carmustine monotherapy

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

Regimen

Study	Dates of enrollment	Evidence
Williams & Einhorn 1977	1973-1975	Non-randomized, fewer than 20 pts

Chemotherapy

• Doxorubicin (Adriamycin) 60 mg/m² IV once on day 1, then 45 mg/m² IV once on day 22
• Lomustine (CCNU) 100 mg/m² PO once on day 1

42-day cycle for up to 5 cycles (maximum doxorubicin cumulative dose of 550 mg/m²)

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 contains dosing details in manuscript PubMed

Panobinostat monotherapy

Regimen

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

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

Targeted therapy

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

21-day cycles

References

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

Sirolimus & Vorinostat

Regimen

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

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

Immunosuppressive therapy

• Sirolimus (Rapamune) 4 mg PO once per day on days 1 to 28

Targeted therapy

• Vorinostat (Zolinza) as follows:
  • Cycle 1: 300 mg PO once per day on days 7 to 28
  • Cycle 2 onwards: 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