Classical Hodgkin lymphoma

Classical Hodgkin Lymphoma

ABVD

Regimen

• Doxorubicin (Adriamycin) 25 mg/m2 IV days 1 & 15
• Bleomycin (Blenoxane) 10 units/m2 IV 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 days 1 & 15
• Dacarbazine (DTIC) 375 mg/m2 IV days 1 & 15

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

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 [http://www.ncbi.nlm.nih.gov/pubmed/1383821 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

Stanford V

Regimen

• Doxorubicin (Adriamycin) 25 mg/m2 IV days 1 & 15
• Vinblastine (Velban) 6 mg/m2 IV days 1 & 15
• Mechlorethamine (Mustargen) 6 mg/m2 IV day 1
• Etoposide (Vepesid) 60 mg/m2 IV days 15 & 16
• Vincristine (Oncovin) 1.4 mg/m2 (maximum of 2mg in any individual dose) IV days 8 & 22
• Bleomycin (Blenoxane) 5 units/m2 IV days 8 & 22
• Prednisone (Sterapred) 40 mg/m2 PO every other day (see note below about taper)
• If dose reduction or delay occurred at any time during chemotherapy, Filgrastim (Neupogen) 5 ug/kg SC (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 150 mg PO BID throughout the course of treatment
• Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID throughout the course of treatment
• Ketoconazole 200 mg PO daily throughout the course of treatment
• Acyclovir 200 mg PO TID throughout the course of treatment

Q28days x 3 cycles

• 36 Gy of consolidative radiation is given from weeks 14-16 to sites of disease ≥ 5 cm and/or to macroscopic nodules in the spleen.
• Taper prednisone by "10 mg every other day between weeks 10 and 12":
  • On week 10, prednisone 30 mg/m2 PO every other day.
  • On week 11, prednisone 20 mg/m2 PO every other day.
  • On week 12, prednisone 10 mg/m2 PO every other day, then off.
• Note: In patients ≥50 years old:
  • Reduce doses of Vincristine (Oncovin) during cycle 3 (weeks 10 & 12 overall) to 1 mg.
  • Reduce doses of Vinblastine (Velban) during cycle 3 (weeks 9 & 11 overall) 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 500-1000. 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.

Escalated Dose BEACOPP

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

Regimen

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

Q21days x 8 cycles

References

1. 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. 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 article(contains protocol) PubMed

ESHAP

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

Regimen

• [[Etoposide (Vepesid) 40 mg/m2 IV days 1-4, infuse over 1 hour
• Methylprenisolone (Solu-Medrol) 500 mg IV days 1-5, infuse over 15-30 minutes
• Cytarabine (Cytosar) 2000 mg/m2 IV day 5, infuse over 2 hours
• Cisplatin (Platinol) 25 mg/m2/day (total dose: 100 mg/m2) IV days 1-4, continuous infusion over 24 hours

Supportive medications

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

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

Lymphocyte predominant Hodgkin Lymphoma

ABVD (Doxorubicin (Adriamycin), Bleomycin (Blenoxane), Vinblastine (Velban), Dacarbazine (DTIC), +/- Rituximab (Rituxan)) (lymphocyte predominant Hodgkin lymphoma)

Regimen

• Doxorubicin (Adriamycin) 25 mg/m2 IV days 1 & 15
• Bleomycin (Blenoxane) 10 units/m2 IV 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 days 1 & 15
• Dacarbazine (DTIC) 375 mg/m2 IV days 1 & 15
• Rituximab (Rituxan) schedule & number of cycles is not well-established. One potential option is 375 mg/m2 IV weekly x 4 weeks on cycle 1 (see single agent rituximab). Use in subsequent cycles is not well-documented.

Q28days x 2-6 cycles based on stage, response, and whether radiation therapy is used.

References

1. See additional references above
2. Savage KJ, Skinnider B, Al-Mansour M, Sehn LH, Gascoyne RD, Connors JM. Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood. 2011 Oct 27;118(17):4585-90. link to original articlePubMed

CHOP (Cyclophosphamide (Cytoxan), Doxorubicin (Adriamycin), Vincristine (Oncovin), Prednisone (Sterapred)) (lymphocyte predominant Hodgkin lymphoma)

Regimen

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV day 1
• Doxorubicin (Adriamycin) 50 mg/m2 IV day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2mg per cycle) IV day 1
• Prednisone (Sterapred) 100 mg PO days 1-5
• Rituximab (Rituxan) 375mg/m2 IV day 1

Q21days x 6-8 cycles (number of cycles for CHOP in LPHL is not well-established)

References

1. Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. link to original article (contains protocol--this was for diffuse large B-cell lymphomas; no primary reference available for use of CHOP in LPHL) PubMed

R-CHOP (Rituximab (Rituxan), Cyclophosphamide (Cytoxan), Doxorubicin (Adriamycin), Vincristine (Oncovin), Prednisone (Sterapred)) (lymphocyte predominant Hodgkin lymphoma)

Regimen

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV day 1
• Doxorubicin (Adriamycin) 50 mg/m2 IV day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2mg per cycle) IV day 1
• Prednisone (Sterapred) 100 mg PO days 1-5
• Rituximab (Rituxan) 375mg/m2 IV day 1

Q21days x 6-8 cycles (number of cycles for R-CHOP in LPHL is not well-established)

References

See references for CHOP

CVP (Cyclophosphamide (Cytoxan), Vincristine (Oncovin), Prednisone (Sterapred)) (lymphocyte predominant Hodgkin lymphoma)

Regimen

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2mg per cycle) IV day 1
• Prednisone (Sterapred) 40 mg/m2 PO days 1-5

Q21days x up to 8 cycles (number of cycles for CVP in LPHL is not well-established)

References

1. Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. link to original article (contains protocol--this was for follicular lymphoma; no primary reference available for use of CVP in LPHL)) PubMed

R-CVP (Rituximab (Rituxan), Cyclophosphamide (Cytoxan), Vincristine (Oncovin), Prednisone (Sterapred)) (lymphocyte predominant Hodgkin lymphoma)

Regimen

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2mg per cycle) IV day 1
• Prednisone (Sterapred) 40 mg/m2 PO days 1-5
• Rituximab (Rituxan) 375mg/m2 IV day 1

Q21days x up to 8 cycles (number of cycles for R-CVP in LPHL is not well-established)

References

See references for CVP

EPOCH (Etoposide (Vepesid), Prednisone (Sterapred), Vincristine (Oncovin), Cyclophosphamide (Cytoxan), Doxorubicin (Adriamycin)) (lymphocyte predominant Hodgkin lymphoma)

Regimen

• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m2 total) continuous IV infusion days 1-4
• Prednisone (Sterapred) 60 mg/m2/day PO days 1-5 (regimen originally was days 1-6, but now is just days 1-5)
• Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m2 total) (sometimes capped at maximum total dose of 2mg per cycle) continuous IV infusion days 1-4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m2 total) continuous IV infusion days 1-4
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 5 (regimen originally was day 6, but now is day 5)
• PCP prophylaxis (choose one)
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID 3 days per week
  • Atovaquone (Mepron) 1500mg PO daily
  • Pentamidine (Nebupent) 300 mg nebulized Q28days
• Filgrastim (Neupogen) 5 mcg/kg SQ daily start day 6 and continue until ANC >5,000/uL past nadir

Q21days x 6-8 cycles

Dose-adjusted EPOCH protocol

• Start cycle 1 as described above
• Obtain twice per week CBCs for nadir measurements
• If nadir ANC >500, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• If nadir ANC <500 on 1 or 2 measurements, use same doses as last cycle
• If nadir ANC <500 on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• And/or if nadir platelet count <25 on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide. The lowest etoposide and doxorubicin would be dosed at is the original cycle 1 dose.
• Can start new cycle Q21days if ANC >1,000 and platelets >100. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.

Historic dose adjustments for hematologic toxicity

These adjustments were in the original paper for standard EPOCH, which are much less relevant due to growth factor support.
If ANC on day 1 is:

• >1,500, full dose cyclophosphamide
• 1,000-1,500, reduce cyclophosphamide by 187 mg/m2 (equal to 25% dose reduction)
• <1,000, hold EPOCH
• If ANC nadir is <500, reduce cyclophosphamide an additional 187 mg/m2
• If ANC nadir is >500 and patient had previously been dose-reduced, increase cyclophosphamide dose by 187 mg/m2

References

1. Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD, et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug;11(8):1573-82 link to original article (contains protocol--this was for non-Hodgkin lymphoma; no primary reference available for use of EPOCH in LPHL) PubMed
2. Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. link to original article (contains protocol--this was for large B-cell lymphomas; no primary reference available for use of EPOCH in LPHL) PubMed
3. Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. link to original article PubMed

R-EPOCH (Rituximab (Rituxan), Etoposide (Vepesid), Prednisone (Sterapred), Vincristine (Oncovin), Cyclophosphamide (Cytoxan), Doxorubicin (Adriamycin)) (lymphocyte predominant Hodgkin lymphoma)

Regimen

• Rituximab (Rituxan) 375mg/m2 IV (Day and frequency not clearly defined in papers, but traditionally given once per cycle in EPOCH for other lymphomas; usually administered as outpatient due to reimbursement. However, note that other rituximab regimens for LPHL seem to be 375 mg/m2 IV weekly x 4 weeks, with no additional doses given after the first four.)
• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m2 total) continuous IV infusion days 1-4
• Prednisone (Sterapred) 60 mg/m2/day PO days 1-5 (regimen originally was days 1-6, but now is just days 1-5)
• Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m2 total) (sometimes capped at maximum total dose of 2mg per cycle) continuous IV infusion days 1-4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m2 total) continuous IV infusion days 1-4
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 5 (regimen originally was day 6, but now is day 5)
• PCP prophylaxis (choose one)
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID 3 days per week
  • Atovaquone (Mepron) 1500mg PO daily
  • Pentamidine (Nebupent) 300 mg nebulized Q28days
• Filgrastim (Neupogen) 5 mcg/kg SQ daily start day 6 and continue until ANC >5,000/uL past nadir

Q21days x 6-8 cycles

Dose-adjusted R-EPOCH protocol

• Start cycle 1 as described above
• Obtain twice per week CBCs for nadir measurements
• If nadir ANC >500, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• If nadir ANC <500 on 1 or 2 measurements, use same doses as last cycle
• If nadir ANC <500 on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• And/or if nadir platelet count <25 on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
• Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide. The lowest etoposide and doxorubicin would be dosed at is the original cycle 1 dose.
• Can start new cycle Q21days if ANC >1,000 and platelets >100. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.

Historic dose adjustments for hematologic toxicity

These adjustments were in the original paper for standard EPOCH, which are much less relevant due to growth factor support.
If ANC on day 1 is:

• >1,500, full dose cyclophosphamide
• 1,000-1,500, reduce cyclophosphamide by 187 mg/m2 (equal to 25% dose reduction)
• <1,000, hold EPOCH
• If ANC nadir is <500, reduce cyclophosphamide an additional 187 mg/m2
• If ANC nadir is >500 and patient had previously been dose-reduced, increase cyclophosphamide dose by 187 mg/m2

References

See references for EPOCH

Single agent Rituximab (Rituxan)

Regimen

• Rituximab (Rituxan) 375mg/m2 IV weekly x 4 weeks

One course of 4 week therapy

Supportive medications

• Acetaminophen 650 mg PO 30 minutes prior to each dose of rituximab
• Diphendyramine (Benadryl) 25 mg PO 30 minutes prior to each dose of rituximab

References

1. Ekstrand BC, Lucas JB, Horwitz SM, Fan Z, Breslin S, Hoppe RT, Natkunam Y, Bartlett NL, Horning SJ. Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. Blood. 2003 Jun 1;101(11):4285-9. link to original article (contains protocol) PubMed
2. Ibom VK, Prosnitz RG, Gong JZ, Moore JO, DeCastro CM, Prosnitz LR, Rizzieri DA, Gockerman JP. Rituximab in lymphocyte predominance Hodgkin's disease: a case series. Blood. 2003 Jun 1;101(11):4285-9. link to original article (contains protocol) PubMed
3. Schulz H, Rehwald U, Morschhauser F, Elter T, Driessen C, Rüdiger T, Borchmann P, Schnell R, Diehl V, Engert A, Reiser M. Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood. 2008 Jan 1;111(1):109-11. link to original article (contains protocol) PubMed