Classical Hodgkin lymphoma

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Untreated

ABVD

ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine

Regimen #1

Phase III

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

Regimen #2, Mounier et al. 2014 (LYSA H34)

Phase III

4-week cycle x 8 cycles

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. 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. Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. link to original article contains verified protocol PubMed
  9. 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
  10. Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, Gabarre J, Casasnovas O, Jaubert J, Colin P, Delmer A, Devidas A, Bachy E, Nicolas-Virelizier E, Aoudjhane A, Humbrecht C, Andre M, Carde P; Lymphoma Study Association (LYSA). ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug;25(8):1622-8. Epub 2014 May 14. link to original article contains verified protocol PubMed

ABVD, DD-DI

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

Regimen, Russo et al. 2014

Phase II

Supportive medications:

21-day cycle x 6 cycles

References

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

B-AVD; AVD-A

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

Regimen

Non-randomized

This was a phase I trial but had >20 patients in the MTD expansion cohort; a phase III trial is underway.

4-weeks cycle x up to 6 cycles

"Consolidative radiotherapy was permitted at the investigator's discretion."

References

  1. Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013 Dec;14(13):1348-56. Epub 2013 Nov 15. link to original article contains verified protocol PubMed
    1. Update: Abstract: Joseph M Connors, MD, Stephen Ansell, Steven I. Park, MD, Michelle A. Fanale, M.D. and Anas Younes. Brentuximab Vedotin Combined with ABVD or AVD for Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma: Long Term Outcomes. ASH Annual Meeting 2014, Abstract 292 link to abstract

BEACOPP

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

Regimen

Phase III

Q21days x 8 cycles

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
    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. 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 #1, Diehl et al. 1998; Diehl et al. 2003; Engert et al. 2009 (GHSG HD9); Borchmann et al. 2011 (GHSG HD12)

Phase III

3-week cycle x 8 cycles

Regimen #2, Viviani et al. 2011; Mounier et al. 2014 (LYSA H34)

Phase III

Escalated phase

Supportive medications:

  • Filgrastim (Neupogen) 300 mcg SC once per day starting day 8, continues until ANC > 1000/uL for 3 consecutive days (Viviani et al. 2011) or until day 14 (Mounier et al. 2014)

3-week cycle x 4 cycles

Standard phase

Supportive medications:

  • Filgrastim (Neupogen) 300 mcg SC once per day starting day 8, continues until ANC > 1000/uL for 3 consecutive days (Viviani et al. 2011) or until day 14 (Mounier et al. 2014)

3-week cycle x 4 cycles

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
    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
  2. Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, Vitolo U, Pulsoni A, Liberati AM, Specchia G, Valagussa P, Rossi A, Zaja F, Pogliani EM, Pregno P, Gotti M, Gallamini A, Rota Scalabrini D, Bonadonna G, Gianni AM; Michelangelo Foundation; Gruppo Italiano di Terapie Innovative nei Linfomi; Intergruppo Italiano Linfomi. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21;365(3):203-12. link to original article contains verified protocol PubMed
  3. Borchmann P, Haverkamp H, Diehl V, Cerny T, Markova J, Ho AD, Eich HT, Mueller-Hermelink HK, Kanz L, Greil R, Rank A, Paulus U, Smardova L, Huber C, Dörken B, Nerl C, Krause SW, Mueller RP, Fuchs M, Engert A. Eight cycles of escalated-dose BEACOPP compared with four cycles of escalated-dose BEACOPP followed by four cycles of baseline-dose BEACOPP with or without radiotherapy in patients with advanced-stage hodgkin's lymphoma: final analysis of the HD12 trial of the German Hodgkin Study Group. J Clin Oncol. 2011 Nov 10;29(32):4234-42. Epub 2011 Oct 11. link to original article PubMed
  4. Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, Gabarre J, Casasnovas O, Jaubert J, Colin P, Delmer A, Devidas A, Bachy E, Nicolas-Virelizier E, Aoudjhane A, Humbrecht C, Andre M, Carde P; Lymphoma Study Association (LYSA). ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug;25(8):1622-8. Epub 2014 May 14. link to original article contains verified protocol PubMed

Brentuximab vedotin (Adcetris)

Regimen, Yasenchak et al. 2013

Phase II

21-day cycle up to 16 cycles

References

  1. Abstract: Christopher A. Yasenchak, MD, Robert Chen, MD, Jeff P. Sharman, MD, Ralph V. Boccia, MD, Beata Holkova, MD, Peter J. Rosen, MD, Jonathan W. Friedberg, MD, Megan M. O'Meara, MD and Andres Forero-Torres, MD. A Phase 2 Study Of Single-Agent Brentuximab Vedotin For Front-Line Therapy Of Hodgkin Lymphoma In Patients Age 60 Years and Above: Interim Results. ASH 2013 Abstract 4389 link to abstract
    1. Update: Abstract: Andres Forero-Torres, MD, Beata Holkova, MD, Jeff P. Sharman, MD, Jonathan W. Friedberg, MD, Maurice J. Berkowitz, MD, William Fintel, MD, Robert Chen, MD, Ralph V. Boccia, MD, Mansoor Saleh, MD, Neil Josephson, MD, Maria Corinna Palanca-Wessels, MD, PhD and Christopher A. Yasenchak, MD. Brentuximab Vedotin Monotherapy and in Combination with Dacarbazine in Frontline Treatment of Hodgkin Lymphoma in Patients Aged 60 Years and Above: Interim Results of a Phase 2 Study. ASH 2014 Abstract 294 link to abstract

BV-ABVD

BV-ABVD: Brentuximab Vedotin, Adriamycin, Bleomycin, Vinblastine, Dacarbazine

Regimen, Federico et al. 2014

Phase II, <20 patients reported

Brentuximab vedotin portion

3-week cycle x 2 cycles, followed by:

ABVD portion

4-week cycle x 3 to 6 cycles based on stage, +/- radiation therapy

References

  1. Abstract: Massimo Federico, Emanuela Anna Pesce, Francesco Merli, Stefano Luminari, Stephane Chauvie, Cinzia Pellegrini, Luigi Marcheselli, Isabella Capodanno, Fiorella Ilariucci, Massimiliano Salati, Lisa Argnani, Pier Luigi Zinzani. A pilot phase II study with brentuximab vedotin followed by ABVD in patients with previously untreated Hodgkin lymphoma: A preliminary report. J Clin Oncol 32:5s, 2014 (suppl; abstr 8507) link to original abstract

ChIVPP

ChIVPP: ChlorambucIl, Vinblastine, Procarbazine, Prednisone

Regimen

Phase II

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

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

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

ABVD

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
    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. 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. 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

Q28days x 6 cycles

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 content property of HemOnc.org
  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

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

Regimen #2, Kasamon et al. 2012

Phase II

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

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.

Dose reductions and delayed treatment:

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

Supportive medications:

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
  2. Retrospective: Anastasia A, Carlo-Stella C, Corradini P, Salvi F, Rusconi C, Pulsoni A, Hohaus S, Pregno P, Viviani S, Brusamolino E, Luminari S, Giordano L, Santoro A. Bendamustine for Hodgkin lymphoma patients failing autologous or autologous and allogeneic stem cell transplantation: a retrospective study of the Fondazione Italiana Linfomi. Br J Haematol. 2014 Mar 7. [Epub ahead of print] link to original article PubMed

Brentuximab vedotin (Adcetris)

Regimen #1, Rothe et al. 2012; Gopal et al. 2012; Younes et al. 2012

Phase II

Supportive medications:

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

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

Regimen #2, Schoder et al. 2013

Phase II

4-week cycle x 2 cycles

Optimal responders (normalization of PET) proceeded to autologous stem cell transplant with BEAM, CBV, or high dose chemoradiotherapy. Suboptimal responders proceeded to receive two cycles of augmented ICE (not described in abstract) prior to transplant.

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
    1. Update: Abstract: Robert Chen, Scott E. Smith, Stephen M Ansell, Joseph D Rosenblatt, Kerry J. Savage, Joseph M. Connors, Andreas Engert, Emily K. Larsen, Dirk Huebner, Eric L. Sievers, Anas Younes. Three-Year Follow-Up Data and Characterization Of Long-Term Remissions From An Ongoing Phase 2 Study Of Brentuximab Vedotin In Patients With Relapsed Or Refractory Hodgkin Lymphoma. Blood Nov 2013,122(21)4382. link to abstract
  2. Gopal AK, Ramchandren R, O'Connor OA, Berryman RB, Advani RH, Chen R, Smith SE, Cooper M, Rothe A, Matous JV, Grove LE, Zain J. Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood. 2012 Jul 19;120(3):560-8. Epub 2012 Apr 17. link to original article contains verified protocol PubMed
  3. 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
  4. Gibb A, Jones C, Bloor A, Kulkarni S, Illidge T, Linton K, Radford J. Brentuximab vedotin in refractory CD30+ lymphomas: a bridge to allogeneic transplantation in approximately one quarter of patients treated on a Named Patient Programme at a single UK center. Haematologica. 2013 Apr;98(4):611-4. Epub 2012 Oct 12. link to original article contains verified protocol PubMed
  5. Abstract: Heiko Schoder, John F. Gerecitano, Paul Hamlin, Steven M. Horwitz, Matthew J Matasar, Vahakn S Keskinyan, Susan McCall, Ariela Noy, M. Lia Palomba, Carol S. Portlock, David J Straus, Joachim Yahalom, Anas Younes, Andrew D Zelenetz, Craig H. Moskowitz. FDG-PET Adapted Sequential Therapy With Brentuximab Vedotin and Augmented ICE Followed By Autologous Stem Cell Transplant For Relapsed and Refractory Hodgkin Lymphoma. Blood Nov 2013,122(21)2099 link to abstract

DHAP

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

Regimen

Phase II

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:

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.

Supportive medications:

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

Supportive medications:

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

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

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, Bartlett et al. 2007 (CALGB 59804)

Phase II

Transplant-naive patients

Q21days x 2 to 6 cycles

Post-transplant patients

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

GVP

GVP: Gemcitabine, Vinorelbine, Prednisolone

Regimen

Phase II

28-day cycle x 4 cycles

References

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

ICE

ICE: Ifosfamide, Carboplatin, Etoposide

Regimen

Phase II

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

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

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 #1, Fernández-Jiménez et al. 1999 & Martín et al. 2001

Phase II

4-week cycle x 2 to 3 cycles

Regimen #2, Colwill et al. 1995

Phase II

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. Fernández-Jiménez MC, Canales MA, Ojeda E, de Bustos JG, Aguado MJ, Hernández-Navarro F. Salvage chemotherapy with mini-BEAM for relapsed or refractory Hodgkin's disease prior to autologous peripheral blood stem cell transplantation. Haematologica. 1999 Nov;84(11):1007-11. link to original article contains verified protocol PubMed
    1. Update: Martín A, Fernández-Jiménez MC, Caballero MD, Canales MA, Pérez-Simón JA, García de Bustos J, Vázquez L, Hernández-Navarro F, San Miguel JF. Long-term follow-up in patients treated with Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease. Br J Haematol. 2001 Apr;113(1):161-71. link to original article contains protocol PubMed

Sirolimus & Vorinostat

Regimen

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.

28-day cycles

References

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

Nodular lymphocyte predominant Hodgkin Lymphoma

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