Diffuse large B-cell lymphoma - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines.

67 regimens on this page 85 variants on this page

Untreated

ACOMLA

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ACOMLA: Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Methotrexate, Leucovorin (Folinic acid), Ara-C (Cytarabine)

Study	Evidence	Comparator
Newcomer et al. 1982	Randomized, <20 patients	CHOP-B

References

1. Newcomer LN, Cadman EC, Nerenberg MI, Chen M, Bertino JR, Farber LR, Prosnitz LR. Randomized study comparing doxorubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (ACOMLA) with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-B) in the treatment of diffuse histiocytic lymphoma. Cancer Treat Rep. 1982 Jun;66(6):1279-84. PubMed

CAP-BOP, COP-BLAM

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CAP-BOP: Cyclophosphamide, Adriamycin (Doxorubicin), Procarbazine, Bleomycin, Oncovin (Vincristine), Prednisone
COP-BLAM: Cyclophosphamide, Oncovin (Vincristine), Prednisone, BLeomycin, Adriamycin (Doxorubicin), Matulane (Procarbazine),

Study	Evidence
Laurence et al. 1982	Phase II
Armitage et al. 1986	Phase II
Boyd et al. 1988	Phase II

References

1. Laurence J, Coleman M, Allen SL, Silver RT, Pasmantier M. Combination chemotherapy of advanced diffuse histiocytic lymphoma with the six-drug COP-BLAM regimen. Ann Intern Med. 1982 Aug;97(2):190-5. link to original article PubMed
2. Armitage JO, Weisenburger DD, Hutchins M, Moravec DF, Dowling M, Sorensen S, Mailliard J, Okerbloom J, Johnson PS, Howe D, et al. Chemotherapy for diffuse large-cell lymphoma--rapidly responding patients have more durable remissions. J Clin Oncol. 1986 Feb;4(2):160-4. link to original article PubMed
3. Boyd DB, Coleman M, Papish SW, Topilow A, Kopel SK, Bernhardt B, Files JC, Schwartz S, Gaynor M, McDermott D, et al. COPBLAM III: infusional combination chemotherapy for diffuse large-cell lymphoma. J Clin Oncol. 1988 Mar;6(3):425-33. link to original article PubMed

CCOP

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CCOP: Cyclophosphamide, Caelyx (Liposomal Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study	Evidence
Martino et al. 2002	Phase II

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV once over 30 minutes on day 1
• Doxorubicin liposomal (Doxil) 30 mg/m2 IV once over 1 hour on day 1
• Vincristine (Oncovin) 2 IV once over 15 minutes on day 1
• Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5

21-day cycles x 6 to 8 cycles

References

1. Martino R, Perea G, Caballero MD, Mateos MV, Ribera JM, de Oteyza JP, Arranz R, Terol MJ, Sierra J, San Miguel JF. Cyclophosphamide, pegylated liposomal doxorubicin (Caelyx), vincristine and prednisone (CCOP) in elderly patients with diffuse large B-cell lymphoma: results from a prospective phase II study. Haematologica. 2002 Aug;87(8):822-7. link to original article contains verified protocol PubMed

CHOEP

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CHOEP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone

Synonyms: CHOPE, VACOP

Structured Concept: C9702 (NCI-T), C0212922(NCI-MT/UMLS)

Example orders

• Example orders for CHOEP in lymphoma

Regimen

Study	Evidence	Comparator	Efficacy	Toxicity
Köppler et al. 1991	Phase III	hCHOP alternating with IVEP
Pfreundschuh et al. 2004 (NHL-B1)	Phase III	CHOP-21;CHOP-14	Seems to have superior EFS	Seems more toxic
Pfreundschuh et al. 2004 (NHL-B2)	Phase III	CHOP-21;CHOP-14	Seems not superior	Seems more toxic

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
• Vincristine (Oncovin) 2 mg IV once on day 1
• Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
• Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
• Patients with initial bulky disease (mass conglomerate at least 7.5 cm) received 36 Gy radiation therapy and to extranodal sites of disease when possible

Supportive medications:

• For 14-day cycles: Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13
• Filgrastim (Neupogen) use for 21-day cycles is by discretion of ordering physician

14 or 21-day cycles x 6 cycles, next cycle to start as long as WBC is >2.5 and platelets >80

• CHOEP-14 uses 14-day cycles; CHOEP-21 uses 21-day cycles

References

1. Köppler H, Pflüger KH, Eschenbach I, Pfab R, Birkmann J, Zeller W, Steinhauer EU, Gropp C, Oehl S, Lötzke E, et al. Sequential versus alternating chemotherapy for high grade non-Hodgkin's lymphomas: a randomized multicentre trial. Hematol Oncol. 1991 Jul-Oct;9(4-5):217-23. PubMed
2. Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains verified protocol PubMed
3. Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. link to original article contains verified protocol PubMed

CHOP-BCG

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CHOP-BCG: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Bacillus Calmette-Guérin

Study	Evidence	Comparator
Jones et al. 1979	Phase III	CHOP-Bleo
Jones et al. 1979	Phase III	COP-Bleo

References

1. Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Butler JJ, Byrne GE Jr, Moon TE, Fisher R, Haskins CL, Coltman CA Jr. Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study. Cancer. 1979 Feb;43(2):417-25. contains verified protocol PubMed

CHOP-Bleo

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CHOP-Bleo: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Bleomycin
BACOP: Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone

Study	Evidence	Comparator
Rodriguez et al. 1977	Phase II
Skarin et al. 1977	Phase II
Jones et al. 1979	Phase III	CHOP-BCG
Jones et al. 1979	Phase III	COP-Bleo
Newcomer et al. 1982	Randomized, <20 patients	ACOMLA

References

1. Rodriguez V, Cabanillas F, Burgess MA, McKelvey EM, Valdivieso M, Bodey GP, Freireich EJ. Combination chemotherapy ("CHOP-Bleo") in advanced (non-Hodgkin) malignant lymphoma. Blood. 1977 Mar;49(3):325-33. link to original article PubMed
2. Skarin AT, Rosenthal DS, Moloney WC, Frei E 3rd. Combination chemotherapy of advanced non-Hodgkin lymphoma with bleomycin, adriamycin, cyclophosphamide, vincristine, and prednisone (BACOP). Blood. 1977 May;49(5):759-70. link to original article PubMed
3. Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Butler JJ, Byrne GE Jr, Moon TE, Fisher R, Haskins CL, Coltman CA Jr. Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study. Cancer. 1979 Feb;43(2):417-25. contains verified protocol PubMed
4. Newcomer LN, Cadman EC, Nerenberg MI, Chen M, Bertino JR, Farber LR, Prosnitz LR. Randomized study comparing doxorubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (ACOMLA) with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-B) in the treatment of diffuse histiocytic lymphoma. Cancer Treat Rep. 1982 Jun;66(6):1279-84. PubMed

C-MOPP

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C-MOPP: CyclophosphaMide, Oncovin (Vincristine), Procarbazine, Prednisone

Study	Evidence
DeVita et al. 1975	Phase II

References

1. DeVita VT Jr, Canellos GP, Chabner B, Schein P, Hubbard SP, Young RC. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet. 1975 Feb 1;1(7901):248-50. PubMed]

COP-Bleo

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COP-Bleo: Cyclophosphamide, Oncovin (Vincristine), Prednisone, Bleomycin

Study	Evidence	Comparator
Jones et al. 1979	Phase III	CHOP-BCG
Jones et al. 1979	Phase III	CHOP-Bleo

References

1. Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Butler JJ, Byrne GE Jr, Moon TE, Fisher R, Haskins CL, Coltman CA Jr. Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study. Cancer. 1979 Feb;43(2):417-25. contains verified protocol PubMed

COPP

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COPP: Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone

Regimen

Study	Evidence	Comparator
Stein et al. 1974	Phase III	VP

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

References

1. Stein RS, Moran EM, Desser RK, Miller JB, Golomb HM, Ultmann JE. Combination chemotherapy of lymphomas other than Hodgkin's disease. Ann Intern Med. 1974 Nov;81(5):601-8. link to original article PubMed

CVP

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CVP: Cyclophosphamide, Vincristine, Prednisone

Synonyms: COP, COP protocol 2, VCP

Structured Concept: C9573 (NCI-T), C0056633 (NCI-MT/UMLS)

Regimen

Study	Evidence
Bagley et al. 1972	Phase II

• Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
• Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5

21-day cycles

References

1. Bagley CM Jr, Devita VT Jr, Berard CW, Canellos GP. Advanced lymphosarcoma: intensive cyclical combination chemotherapy with cyclophosphamide, vincristine, and prednisone. Ann Intern Med. 1972 Feb;76(2):227-34. link to original article PubMed

DA-EPOCH

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DA-EPOCH: Dose Adjusted Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)

Synonyms: CHEOP

Structured Concept: C63779 (NCI-T), C1880475 (NCI-MT/UMLS)

Regimen

Study	Evidence
Wilson et al. 2002	Phase II

• Etoposide (Vepesid) 50 mg/m2/day (total dose of 200 mg/m2) IV continuous infusion on days 1 to 4
• Prednisone (Sterapred) 60 mg/m2 PO BID on days 1 to 5
• Vincristine (Oncovin) 0.4 mg/m2/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1 to 4
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV once over 15 minutes on day 5
• Doxorubicin (Adriamycin) 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1 to 4

Supportive medications:

• Filgrastim (Neupogen) 5 mcg/kg SQ once per day, starting on day 6 and continuing until ANC >5,000/uL past nadir
• PCP prophylaxis with any one of the following:
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO BID 3 days per week
  • Atovaquone (Mepron) 1500 mg PO once per day
  • Pentamidine (Nebupent) 300 mg nebulized every 28 days

21-day cycles x 6 to 8 cycles

Dose-adjustments for EPOCH protocol:

• Start cycle 1 as described above.
• Obtain CBCs twice per week 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 every 21 days 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.

References

1. 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 verified protocol PubMed

HOP

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HOP: Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Study	Evidence	Comparator
McKelvey et al. 1976	Phase III	CHOP

References

1. McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93. PubMed

MACOP-B

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MACOP-B: Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone, Bleomycin

Regimen

Phase III

• Methotrexate (MTX) 400 mg/m2 IV once per week on weeks 2, 6, 10
• Doxorubicin (Adriamycin) 50 mg/m2 IV once per week on weeks 1, 3, 5, 7, 9, 11
• Cyclophosphamide (Cytoxan) 350 mg/m2 IV once per week on weeks 1, 3, 5, 7, 9, 11
• Vincristine (Oncovin) 1.4 mg/m2 IV once per week on weeks 2, 4, 6, 8, 10, 12
• Prednisone (Sterapred) 75 mg PO once per day, tapered over last 15 days (schedule not reported)
• Bleomycin (Blenoxane) 10 units/m2 IV once per week on weeks 4, 8, 12

CNS prophylaxis (for patients with bone marrow involvement):

• Methotrexate (MTX) 12 mg IV

Supportive medications:

• • Trimethoprim/Sulfamethoxazole (Bactrim DS) 2 tablets (not specified if SS or DS) PO BID

One 12-week course

References

1. Klimo P, Connors JM. MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med. 1985 May;102(5):596-602. link to original article PubMed
2. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. link to original article PubMed
3. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study. Ann Oncol. 1994;5 Suppl 2:91-5. PubMed
4. Sertoli MR, Santini G, Chisesi T, Congiu AM, Rubagotti A, Contu A, Salvagno L, Coser P, Porcellini A, Vespignani M, et al. MACOP-B versus ProMACE-MOPP in the treatment of advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group. J Clin Oncol. 1994 Jul;12(7):1366-74. link to original article PubMed

PEN

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PEN: Prednisone, Etoposide, Novantrone (Mitoxantrone)

Regimen

Study	Evidence
Goss et al. 1995	Phase II

References

1. Goss P, Burkes R, Rudinskas L, King M, Chow W, Myers R, Davidson M, Poldre P, Crump M, Sutton D, et al. A phase II trial of prednisone, oral etoposide, and novantrone (PEN) as initial treatment of non-Hodgkin's lymphoma in elderly patients. Leuk Lymphoma. 1995 Jun;18(1-2):145-52. link to original article PubMed

Relapsed/refractory

DICE

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DICE: Dexamethasone, Ifosfamide, Carboplatin, Etoposide

Regimen

Study	Evidence
Goss et al. 1991	Phase II
Coleman et al. 2001	Phase II

References

1. Goss PE, Shepherd FA, Scott JG, Warner E, Baker MA, Sutton D, Farquharson HA, Buick S, Sutcliffe S. Dexamethasone/ifosfamide/cisplatin/etoposide (DICE) as therapy for patients with advanced refractory non-Hodgkin's lymphoma: preliminary report of a phase II study. Ann Oncol. 1991 Jan;2 Suppl 1:43-6. PubMed
2. Coleman M, Leonard J, Shuster MW, Kaufman TP. DICE (dexamethasone, ifosfamide, cisplatin, etoposide) infusional chemotherapy for refractory or relapsed non-Hodgkin's lymphoma (NHL). Eur J Haematol Suppl. 2001 Jul;64:41-5. PubMed

DICEP

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DICEP: Dose Intensive, Cyclophosphamide, Etoposide, Platinol (Cisplatin)

Regimen

Study	Evidence
Neidhart et al. 1994	Phase II

References

1. Neidhart JA, Kubica R, Stidley C, Pfile J, Clark D, Rinehart J. Multiple cycles of dose-intensive cyclophosphamide, etoposide, and cisplatinum (DICEP) produce durable responses in refractory non-Hodgkin's lymphoma. Cancer Invest. 1994;12(1):1-11. PubMed

DVIP

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DVIP: Dexamethasone, VP-16 (Etoposide), Ifosfamide, Platinol (Cisplatin)

Regimen

Study	Evidence
Haim et al. 1992	Phase II

References

1. Haim N, Rosenblatt E, Wollner M, Ben-Shahar M, Epelbaum R, Robinson E. Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin. Cancer Chemother Pharmacol. 1992;30(3):243-4. PubMed

EPIC

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EPIC: Etoposide, Prednisolone, Ifosfamide, Carboplatin

Regimen

Study	Evidence
Hickish et al. 1993	Phase II
Richardson et al. 1994	Phase II, <20 patients

References

1. Hickish T, Roldan A, Cunningham D, Mansi J, Ashley S, Nicolson V, Gore ME, Catovsky D, Smith IE. EPIC: an effective low toxicity regimen for relapsing lymphoma. Br J Cancer. 1993 Sep;68(3):599-604. link to PMC article PubMed
2. Richardson DS, Tighe M, Cull G, Johnson SA, Phillips MJ. Salvage chemotherapy for relapsed and resistant lymphoma with a carboplatin containing schedule--EPIC. Hematol Oncol. 1994 May-Jun;12(3):125-8. PubMed

ESHA

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ESHA: Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine)

Regimen

Study	Evidence	Comparator	Efficacy
Velasquez et al. 1994	Phase III	ESHAP	Inferior RR

• Etoposide (Vepesid) 40 mg/m2 IV over 1 hour once per day on days 1 to 4
• Methylprednisolone (Solumedrol) 250 to 500 mg IV over 15 minutes once per day on days 1 to 5
• Cytarabine (Cytosar) 2000 mg/m2 IV over 2 hours once on day 5

Supportive medications:

• At least 1 liter normal saline with 25 to 50 g Mannitol once per day throughout chemotherapy
• Metoclopramide (Reglan) 0.5 to 1 mg/kg "given regularly"

21 to 28 day cycles ("after recovery of the toxic effects") x 6 to 8 cycles

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 article contains verified protocol PubMed