Classical Hodgkin lymphoma

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Classical Hodgkin Lymphoma

ABVD

ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine

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.

• 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. 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 mcg/kg SC daily 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 150 mg PO BID throughout the course of treatment
• Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID throughout the course of treatment
• Acyclovir 200 mg PO TID throughout the course of treatment
• Ketoconazole 200 mg PO daily 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 2-4 weeks after chemotherapy is complete and is given to sites of disease ≥ 5 cm and/or to macroscopic nodules in the spleen.
• Taper prednisone 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 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 500-1000. 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

BEACOPP

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

Regimen

• Bleomycin (Blenoxane) 10 units/m2 IV day 8
• Etoposide (Vepesid) 100 mg/m2 IV days 1-3
• Doxorubicin (Adriamycin) 25 mg/m2 IV day 1
• Cyclophosphamide (Cytoxan) 650 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

• Example orders for BEACOPP in Hodgkin lymphoma

References

1. 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

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

• Example orders for escalated dose BEACOPP in Hodgkin lymphoma

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 articlecontains protocol PubMed

ChIVPP

ChIVPP: Chlorambucil, Vinblastine, Procarbazine, Prednisone

Regimen

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

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

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

Q28days x 8 cycles

• 25-40 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]

C-MOPP/ABVD

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

Regimen

C-MOPP:

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

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 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. 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

DHAP

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

Regimen

• Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1
• Cytarabine (Cytosar) 2000 mg/m2 IV given over 3 hours Q12H x 2 doses on day 2
• Dexamethasone 40 mg PO/IV over 15 minutes days 1-4
• Normal saline with mannitol 50 g/L given at 250 mL/H x 36 hours, starting 6 hours before Cisplatin (Platinol) infusion was started

Q21-28days (depending on degree of myelosuppression) x 6-10 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 1.5-2.0	-	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

• Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1
• Cytarabine (Cytosar) 2000 mg/m2 IV given over 3 hours Q12H x 2 doses on day 2
• Dexamethasone 40 mg IV days 1-4
• Hydration at 250 mL/H started 2-6 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 days 1 & 2
• Filgrastim (Neupogen) 5 mcg/kg SQ daily, start 24 hours after last dose of cytarabine 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.

• 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.

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 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

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

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

GCD

GCD: Gemcitabine, Carboplatin, Dexamethasone

Regimen

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

Q21days x up to 4 cycles

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

Dose modifications:

• If on day 8, platelets are 50-100 or ANC 500-1000: 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

Transplant-naive patients:

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

Q21days x 2-6 cycles

Post-transplant patients:

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

Q21days x 2-6 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 6-10 minutes days 1 & 8
  • Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes days 1 & 8
  • Doxorubicin liposomal (Doxil) 15 mg/m2 IV over 30-60 minutes days 1 & 8
• Dose level 2:
  • Vinorelbine (Navelbine) 20 mg/m2 IV over 6-10 minutes days 1 & 8
  • Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes days 1 & 8
  • Doxorubicin liposomal (Doxil) 20 mg/m2 IV over 30-60 minutes days 1 & 8
• Dose level -1:
  • Vinorelbine (Navelbine) 15 mg/m2 IV over 6-10 minutes days 1 & 8
  • Gemcitabine (Gemzar) 800 mg/m2 IV over 30 minutes days 1 & 8
  • Doxorubicin liposomal (Doxil) 10 mg/m2 IV over 30-60 minutes 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/GM-CSF).
  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 50-100 or ANC 500-1000: 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

• Etoposide (Vepesid) 100 mg/m2 IV days 1-3
• Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV day 2
• Ifosfamide (Ifex) 5 g/m2 IV continuous infusion over 24 hours on day 2; mixed in same solution as Mesna (Mesnex)
• 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 days 5-12
• 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

• Ifosfamide (Ifex) 2000 mg/m2 IV over 2 hours days 1-4
• 2L saline solution hyperhydration days 1-4
• Mesna (Mesnex) 2600 mg/m2 IV days 1-4
• Gemcitabine (Gemzar) 800 mg/m2 IV days 1-4
• Vinorelbine (Navelbine) 20 mg/m2 IV day 1
• Prednisone (Sterapred) 100 mg PO days 1-4
• Filgrastim (Neupogen) (dose not specified, but could assume 5 mcg/kg) SC days 7-12, 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

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

Q21-28 days x up to 6 cycles in patients who respond

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

• Carmustine (BiCNU) 60 mg/m2 IV over 30 minutes day 1
• Etoposide (Vepesid) 75 mg/m2 IV over 30 minutes days 2-5
• Cytarabine (Cytosar) 100 mg/m2 IV Q12H on days 2-5
• Melphalan (Alkeran) 30 mg/m2 IV over 15 minutes day 6
• If febrile neutropenia occurred during previous cycle: Ciprofloxacin (Cipro) 500 mg PO daily
• Patients were transfused to keep Hb ≥8, platelets ≥20
• There was no routine use of G-CSF or GM-CSF

Q4-6weeks 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

MOPP

MOPP: Mustargen, Oncovin, Procarbazine, Prednisone

Regimen

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

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

Lymphocyte predominant Hodgkin Lymphoma

ABVD

ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine

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

CHOP: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone

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

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

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone

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

CVP: Cyclophosphamide, Vincristine, Prednisone

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

R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

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

EPOCH: Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin

Regimen, original EPOCH protocol (Wilson, et al. 1993)

• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m2 total) IV continuous infusion on days 1-4
• Prednisone (Sterapred) 60 mg/m2/day PO on 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) IV continuous infusion on days 1-4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m2 total) IV continuous infusion on 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

Alternate regimen, as listed for the dose-adjusted EPOCH protocol (Wilson, et al. 2002)

• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m2 total) IV continuous infusion on days 1-4
• Prednisone (Sterapred) 60 mg/m2 PO BID on days 1-5
• Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m2 total) (not capped in the paper, but sometimes capped at a maximum total dose of 2mg per cycle) IV continuous infusion on days 1-4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m2 total) IV continuous infusion on days 1-4
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on 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-adjustments for 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 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 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

R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin

Regimen, based on original EPOCH protocol (Wilson, et al. 1993)

• Rituximab (Rituxan) 375mg/m2 IV once per cycle (usually given as outpatient due to reimbursement issues)
• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m2 total) IV continuous infusion on days 1-4
• Prednisone (Sterapred) 60 mg/m2/day PO on 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) IV continuous infusion on days 1-4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m2 total) IV continuous infusion on 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

Alternate regimen, as listed for the dose-adjusted EPOCH protocol (Wilson, et al. 2002)

• Rituximab (Rituxan) 375mg/m2 IV once per cycle (usually given as outpatient due to reimbursement issues)
• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m2 total) IV continuous infusion on days 1-4
• Prednisone (Sterapred) 60 mg/m2 PO BID on days 1-5
• Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m2 total) (not capped in the paper, but sometimes capped at a maximum total dose of 2mg per cycle) IV continuous infusion on days 1-4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m2 total) IV continuous infusion on days 1-4
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on 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