Classical Hodgkin lymphoma

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Untreated

ABVD

ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine

Regimen

Phase III

• Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
• Bleomycin (Blenoxane) 10 units/m2 IV once on days 1 & 15 (1 unit test dose with cycle 1 doses, 60 minutes prior to remainder of full dose)
• Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
• Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 15

Q28days x 4 to 6 cycles based on stage, response, and whether radiation therapy is used.

• Example orders for ABVD in Hodgkin lymphoma

References

1. Bonadonna G, Santoro A. ABVD chemotherapy in the treatment of Hodgkin's disease. Cancer Treat Rev. 1982 Mar;9(1):21-35. (no link to original article available) PubMed
2. Bonadonna G. Chemotherapy strategies to improve the control of Hodgkin's disease: the Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res. 1982 Nov;42(11):4309-20. link to original article contains protocol PubMed
3. Santoro A, Bonadonna G, Valagussa P, Zucali R, Viviani S, Villani F, Pagnoni AM, Bonfante V, Musumeci R, Crippa F et al. Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy. J Clin Oncol. 1987 Jan;5(1):27-37. link to original article PubMed
4. 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
5. Carde P, Hagenbeek A, Hayat M, Monconduit M, Thomas J, Burgers MJ, Noordijk EM, Tanguy A, Meerwaldt JH, Le Fur R et al. Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol. 1993 Nov;11(11):2258-72. link to original article PubMed
6. Update: Bonadonna G, Bonfante V, Viviani S, Di Russo A, Villani F, Valagussa P. ABVD plus subtotal nodal versus involved-field radiotherapy in early-stage Hodgkin's disease: long-term results. J Clin Oncol. 2004 Jul 15;22(14):2835-41. link to original article contains protocol PubMed
7. Engert A, Franklin J, Eich HT, Brillant C, Sehlen S, Cartoni C, Herrmann R, Pfreundschuh M, Sieber M, Tesch H, Franke A, Koch P, de Wit M, Paulus U, Hasenclever D, Loeffler M, Müller RP, Müller-Hermelink HK, Dühmke E, Diehl V. Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol. 2007 Aug 10;25(23):3495-502. link to original article contains protocol PubMed
8. Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Stiff PJ, Cheson BD, Gospodarowicz M, Advani R, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized Phase III Trial of ABVD Versus Stanford V With or Without Radiation Therapy in Locally Extensive and Advanced-Stage Hodgkin Lymphoma: An Intergroup Study Coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013 Feb 20;31(6):684-91. Epub 2012 Nov 26. link to original article PubMed

BEACOPP

BEACOPP: Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Oncovin, Procarbazine, Prednisone

Regimen

Phase III

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

Q21days x 8 cycles

• Example orders for BEACOPP in Hodgkin lymphoma

References

1. 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
2. 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
3. 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

BEACOPP, escalated dose

BEACOPP: Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Oncovin, Procarbazine, Prednisone

Regimen

Phase III

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

Q21days x 8 cycles

• Example orders for escalated dose BEACOPP in Hodgkin lymphoma

References

1. 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
2. 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
3. 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

ChIVPP

ChIVPP: ChlorambucIl, Vinblastine, Procarbazine, Prednisone

Regimen

Phase II

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

Q28days to complete remission plus 2 cycles; minimum of 6 cycles and maximum of 8 cycles

References

1. The International ChlVPP Treatment Group. ChlVPP therapy for Hodgkin's disease: experience of 960 patients. Ann Oncol. 1995 Feb;6(2):167-72. link to original article contains protocol PubMed

C-MOPP/ABV

C-MOPP: CyclophosphaMide, Oncovin, Procarbazine, Prednisone
ABV: Adriamycin, Bleomycin, Vinblastine

Regimen

Phase II

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

Q28days x 8 cycles

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

References

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

COPP-ABVD, C-MOPP/ABVD

COPP: Cyclophosphamide, Oncovin, Procarbazine, Prednisone C-MOPP: CyclophosphaMide, Oncovin, Procarbazine, Prednisone
ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine

Regimen

Phase III

COPP

• Cyclophosphamide (Cytoxan) 500 mg/m2 IV drip days 1 & 8
• Vincristine (Oncovin) 1.4 mg/m2 (maximum of 2 mg per dose) IV once on days 1 & 8
• Procarbazine (Matulane) 100 mg/m2 (maximum of 150 mg per dose) 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

Q28days x 5 total cycles of C-MOPP, alternating with 5 total cycles of ABVD

ABVD

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

Q28days x 5 total cycles of ABVD, alternating with 5 total cycles of C-MOPP

• 30 Gy of involved field radiation after completion of chemotherapy was given to patients with bulky (≥10 cm maximum diameter) disease

Delayed treatment and discontinuations:

• Treatment was postponed for at least 1 week or until recovery if:
  • Pretreatment ANC was <1500
  • Platelet count was <100 x 10^3
  • AST/S-GOT was >100 IU/L
  • Total bilirubin was >2
• Vincristine (Oncovin) and Vinblastine (Velban) were temporarily discontinued if patients had grade 2 or greater neurotoxicity (e.g. motor weakness, paresthesia, constipation)
• Doxorubicin (Adriamycin) was discontinued if cardiac LV ejection fraction was <50%
• Bleomycin (Blenoxane) was stopped if the PaO2 was less than 70 mmHg or if it decreased more than 10 mmHg from the previous measurement
• Note: Dacarbazine (DTIC) 250 mg/m2 was used at this dose reduction based on experiences in a pilot study in which there was severe emesis with Dacarbazine (DTIC) 375 mg/m2.

References

1. 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
2. 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. 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). The Lymphoma Study Group of the Japan Clinical Oncology Group. Jpn J Clin Oncol. 2000 Mar;30(3):146-52. link to original article contains protocol PubMed
3. 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
4. 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

MOPP

MOPP: Mustargen, Oncovin, Procarbazine, Prednisone

Regimen

Phase III

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

Q28days x 6 cycles

• Example orders for MOPP in Hodgkin lymphoma

References

1. Devita VT Jr, Serpick AA, Carbone PP. Combination chemotherapy in the treatment of advanced Hodgkin's disease. Ann Intern Med. 1970 Dec;73(6):881-95. link to original article contains protocol PubMed
2. 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

RABVD

RABVD: Rituximab, Adriamycin, Bleomycin, Vinblastine, Dacarbazine

Regimen #1, Younes et al. 2012

Phase II

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

Q28days x 6 cycles (except rituximab, which is given for a total of 6 doses)

Regimen #2, Kasamon et al. 2012

Phase II

• Rituximab (Rituxan) 375 mg/m2 IV once per day 1) one week prior to cycle 1 of ABVD; 2) on days 1, 8, 15, 22 of cycle 1; 3) on day 1 of cycles 2, 4, and 6
• Doxorubicin (Adriamycin) 25 mg/m2 IV once per day on days 1 & 15
• Bleomycin (Blenoxane) 10 units/m2 IV once per day on days 1 & 15
• Vinblastine (Velban) 6 mg/m2 IV once per day on days 1 & 15
• Dacarbazine (DTIC) 375 mg/m2 IV once per day on days 1 & 15

Q28days x 6 to 8 cycles

References

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

Stanford V

Regimen

Phase III

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

Supportive medications:

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

Q28days x 3 cycles

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

• Taper Prednisone (Sterapred) by "10 mg every other day between weeks 10 and 12":
  • On week 10, Prednisone (Sterapred) 30 mg/m2 PO every other day.
  • On week 11, Prednisone (Sterapred) 20 mg/m2 PO every other day.
  • On week 12, Prednisone (Sterapred) 10 mg/m2 PO every other day, then off.
• Note: In patients ≥50 years old:
  • Reduce doses of Vincristine (Oncovin) during cycle 3 to 1 mg.
  • Reduce doses of Vinblastine (Velban) during cycle 3 to 4 mg/m2.

Dose reductions and delayed treatment:

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

References

1. Horning SJ, Williams J, Bartlett NL, Bennett JM, Hoppe RT, Neuberg D, Cassileth P. Assessment of the Stanford V regimen and consolidative radiotherapy for bulky and advanced Hodgkin's disease: Eastern Cooperative Oncology Group pilot study E1492. J Clin Oncol. 2000 Mar;18(5):972-80. link to original article contains protocol PubMed
2. Horning SJ, Hoppe RT, Breslin S, Bartlett NL, Brown BW, Rosenberg SA. Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial. J Clin Oncol. 2002 Feb 1;20(3):630-7. link to original article contains protocol PubMed
3. Edwards-Bennett SM, Jacks LM, Moskowitz CH, Wu EJ, Zhang Z, Noy A, Portlock CS, Straus DJ, Zelenetz AD, Yahalom J. Stanford V program for locally extensive and advanced Hodgkin lymphoma: the Memorial Sloan-Kettering Cancer Center experience. Ann Oncol. 2010 Mar;21(3):574-81. link to original article PubMed
4. Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Stiff PJ, Cheson BD, Gospodarowicz M, Advani R, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized Phase III Trial of ABVD Versus Stanford V With or Without Radiation Therapy in Locally Extensive and Advanced-Stage Hodgkin Lymphoma: An Intergroup Study Coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013 Feb 20;31(6):684-91. Epub 2012 Nov 26. link to original article PubMed

Relapsed/refractory

Bendamustine (Treanda)

Regimen

Phase II

• Bendamustine (Treanda) 120 mg/m2 IV over 30 minutes on days 1 & 2

Supportive medications:

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

28-day cycles x up to 6 cycles

References

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

Brentuximab vedotin (Adcetris)

Regimen

Phase II

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

Supportive medications:

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

21-day cycles, given until progression (Rothe et al. 2012) or up to 16 infusions (Younes et al. 2012)

References

1. Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012 Jun 20;30(18):2183-9. Epub 2012 Mar 26. link to original article contains verified protocol PubMed
2. Rothe A, Sasse S, Goergen H, Eichenauer DA, Lohri A, Jäger U, Bangard C, Böll B, von Bergwelt Baildon M, Theurich S, Borchmann P, Engert A. Brentuximab vedotin for relapsed or refractory CD30+ hematologic malignancies: the German Hodgkin Study Group experience. Blood. 2012 Aug 16;120(7):1470-2. Epub 2012 Jul 11. link to original article contains verified protocol PubMed
3. Retrospective: Zinzani PL, Viviani S, Anastasia A, Vitolo U, Luminari S, Zaja F, Corradini P, Spina M, Brusamolino E, Gianni AM, Santoro A, Botto B, Derenzini E, Pellegrini C, Argnani L. Brentuximab vedotin in relapsed/refractory Hodgkin's lymphoma: Italian experience and results of the use in the daily clinic outside clinical trials. Haematologica. 2013 May 3. [Epub ahead of print] link to original article PubMed

DHAP

DHAP: Dexamethasone, High-dose Ara-C, Platinol

Regimen

Phase II

• Dexamethasone 40 mg PO/IV over 15 minutes once per day on days 1 to 4
• Cytarabine (Cytosar) 2000 mg/m2 IV given over 3 hours Q12H x 2 doses on day 2
• Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1

Supportive medications:

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

Q21 to 28days (depending on degree of myelosuppression) x 6 to 10 cycles, with therapy given 4 cycles beyond the maximum antitumor effect

• Aside from the table below, there were no specific cutoff criteria in the paper about dose modifications or delays of treatment.

Dose modifications:

• Patients >70 years old received Cytarabine (Cytosar) dose reduced to 1000 mg/m2

Dose modifications
Event	Cytarabine (Cytosar)	Cisplatin (Platinol)
ANC <200	1000 mg/m2 x 2 doses	100 mg/m2
Platelets <20 x 10^3	1000 mg/m2 x 2 doses	100 mg/m2
Sepsis associated with neutropenia	500 mg/m2 x 1 dose	100 mg/m2
Cr 1.5 to 2.0	-	75 mg/m2
Cr 2.1-3.0	-	50 mg/m2

References

1. Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, Barlogie B. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. link to original article contains protocol PubMed

DHAP - time intensified

DHAP: Dexamethasone, High-dose Ara-C, Platinol

Regimen

Phase II

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

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

Supportive medications:

• Hydration at 250 mL/H started 2 to 6 hours before Cisplatin (Platinol) infusion was started
• Prednisolone acetate 1% eyedrops 1 drop to both eyes TID; start 12 hours before start of Cytarabine (Cytosar) and continued for 2 days after cytarabine administration complete
• Ondansetron (Zofran) 8 mg IV once on days 1 & 2
• Filgrastim (Neupogen) 5 mcg/kg SQ per day, start 24 hours after last dose of Cytarabine (Cytosar) and continue until ANC >2,500 for 3 days

Variable number of days between cycles depending on count recovery x 2 cycles Median time between cycle 1 and 2 was 16 days. The paper did not definitively specify what criteria needed to be fulfilled before cycle 2 was given. Baseline eligibility criteria for the study included WBC >3.5 x 10^3, Hb ≥8, platelets ≥100 x 10^3.

References

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

ESHAP

ESHAP: Etoposide, Solumedrol, High-dose Ara-C, Platinum

Regimen

• Etoposide (Vepesid) 40 mg/m2 IV once per day on days 1 to 4, infuse over 1 hour
• Methylprednisolone (Solumedrol) 500 mg IV once per day on days 1 to 5, infuse over 15 to 30 minutes
• Cytarabine (Cytosar) 2000 mg/m2 IV once on day 5, infuse over 2 hours
• Cisplatin (Platinol) 25 mg/m2/day (total dose: 100 mg/m2) IV once per day on days 1 to 4, continuous infusion over 24 hours

Supportive medications:

• Prednisolone acetate 1% eyedrops 1 drop to both eyes TID; start 15 minutes before Cytarabine (Cytosar) and continue until 48 hours after Cytarabine (Cytosar) is completed.

Q21 to 28 days x 6 to 8 cycles in responding patients

References

1. Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. link to original articlePubMed

Everolimus (Afinitor)

Regimen, Johnston et al. 2010

Phase II

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

Supportive medications:

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

28-day cycles, given until progression or unacceptable toxicity

References

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

GCD +/- R

GCD +/- R: Gemcitabine, Carboplatin, Dexamethasone, Rituximab

Regimen

Phase II

• Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once on days 1 & 8
• Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1
• Dexamethasone 40 mg PO once per day on days 1 to 4
• If disease is CD20 positive: Rituximab (Rituxan) 375 mg/m2 slow IV infusion once on day 8

Supportive medications:

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

Q21days x up to 4 cycles

Dose modifications:

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

References

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

GVD

GVD: Gemcitabine, Vinorelbine, Doxil

Regimen

Phase II

Transplant-naive patients

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

Q21days x 2 to 6 cycles

Post-transplant patients

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

Q21days x 2 to 6 cycles

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

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

Dose modifications:

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

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

References

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

ICE

ICE: Ifosfamide, Carboplatin, Etoposide

Regimen

Phase II

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

Supportive medications:

• Mesna (Mesnex) 5 g/m2 IV continuous infusion over 24 hours on day 2; mixed in same solution as Ifosfamide (Ifex)
• Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 5 to 12
• No dose reductions--treatment is delayed until ANC is >1000 and platelets >50 x 10^3

Q14days x 2 cycles

References

1. Moskowitz CH, Nimer SD, Zelenetz AD, Trippett T, Hedrick EE, Filippa DA, Louie D, Gonzales M, Walits J, Coady-Lyons N, Qin J, Frank R, Bertino JR, Goy A, Noy A, O'Brien JP, Straus D, Portlock CS, Yahalom J. A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood. 2001 Feb 1;97(3):616-23. link to original article contains protocol PubMed

IGEV

IGEV: Ifosfamide, GEmcitabine, Vinorelbine

Regimen

Phase II

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

Supportive medications:

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

Q21days x 4 cycles

References

1. Santoro A, Magagnoli M, Spina M, Pinotti G, Siracusano L, Michieli M, Nozza A, Sarina B, Morenghi E, Castagna L, Tirelli U, Balzarotti M. Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma. Haematologica. 2007 Jan;92(1):35-41. link to original article contains protocol PubMed

MINE

MINE: Mesna, Ifosfamide, Novantrone, Etoposide

Regimen

Phase II

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

Q21 to 28 days x up to 6 cycles in responding patients

References

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

Mini-BEAM

BEAM: BiCNU, Etoposide, Ara-C, Melphalan

Regimen

Phase II

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

Supportive medications:

• If febrile neutropenia occurred during previous cycle: Ciprofloxacin (Cipro) 500 mg PO once per day
• Patients were transfused to keep Hb ≥8, platelets ≥20
• There was no routine use of G-CSF or GM-CSF

Q4 to 6 weeks x 2 cycles prior to intensive therapy and autologous bone marrow transplantation

References

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

Lymphocyte predominant Hodgkin Lymphoma

• Regimens can be found on the separate Lymphocyte-predominant Hodgkin Lymphoma page