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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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. See the DLBCL page for current regimens.

67 regimens on this page 85 variants on this page

Untreated

ABP

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ABP: Adriamycin (Doxorubicin), Bleomycin, Prednisone

Regimen

Study	Evidence	Comparator
Monfardini et al. 1977	Phase III	CVP

References

1. Monfardini S, Tancini G, DeLena M, Villa E, Valagussa P, Bonadonna G. Cyclophosphamide, vincristine, and prednisone (CVP) versus adriamycin, bleomycin, and prednisone (ABP) in stage IV non-Hodgkin's lymphomas. Med Pediatr Oncol. 1977;3(1):67-74. PubMed

ACE

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ACE: Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide

Regimen

Study	Evidence	Comparator
Dumontet et al. 2000	Phase II
Haioun et al. 2009	Phase III	ACVBP

References

1. Dumontet C, Thieblemont C, Espinouse D, Bouafia F, Hequet O, Salles G, Coiffier B. A prospective study of intensive induction therapy with high-dose consolidation in patients with aggressive non-Hodgkin's lymphoma and two or three adverse prognostic factors. Leukemia. 2000 Dec;14(12):2159-65. PubMed
2. Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. link to original article PubMed

ACOMLA

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

Regimen

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

ACVBP

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ACVBP: Adriamycin (Doxorubicin), Cyclophosphamide, Vindesine, Bleomycin, Prednisone

Regimen

Study	Evidence	Comparator
Tilly et al. 2000 (LNH87-1)	Phase III	m-BACOD
Tilly et al. 2003	Phase III	CHOP
Reyes et al. 2005	Phase III	CHOP -> RT
Haioun et al. 2009	Phase III	ACE
Ketterer et al. 2013 (LNH03-1B)	Phase III	ACVBP-R

Induction Regimen

• Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
• Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
• Vindesine (Eldisine) 2 mg/m2 IV once per day on days 1 & 5
• Bleomycin (Blenoxane) 10 units IV once per day on days 1 & 5
• Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5

CNS prophylaxis:

• Methotrexate (MTX) 15 mg intrathecal on day 2

Supportive medications:

• G-CSF or GM-CSF SC once per day on days 6 to 13

21-day cycle x 4 cycles

Consolidation Regimen, part 1

• Methotrexate (MTX) 3000 mg/m2 IV once on day 1

Supportive medications:

• Leucovorin rescue

14-day cycle x 2 cycles, then

Consolidation Regimen, part 2

• Etoposide (Vepesid) 300 mg/m2 IV once on day 1
• Ifosfamide (Ifex) 1500 mg/m2 IV once on day 1

Supportive medications:

• Mesna (Mesnex) "protection" (details not provided)

14-day cycle x 4 cycles, beginning 2 weeks after completion of MTX, then

Consolidation Regimen, part 3

• Cytarabine (Cytosar) 100 mg/m2 SC once per day on days 1 to 4

14-day cycle x 2 cycles, beginning 2 weeks after completion of EI

References

1. Tilly H, Mounier N, Lederlin P, Brière J, Dupriez B, Sebban C, Bosly A, Biron P, Nouvel C, Herbrecht R, Bordessoule D, Coiffier B. Randomized comparison of ACVBP and m-BACOD in the treatment of patients with low-risk aggressive lymphoma: the LNH87-1 study. Groupe d'Etudes des Lymphomes de l'Adulte. J Clin Oncol. 2000 Mar;18(6):1309-15. link to original article PubMed
2. Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. Epub 2003 Aug 14. link to original article contains verified protocol PubMed
3. Reyes F, Lepage E, Ganem G, Molina TJ, Brice P, Coiffier B, Morel P, Ferme C, Bosly A, Lederlin P, Laurent G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte (GELA). ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005 Mar 24;352(12):1197-205. link to original article PubMed
4. Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. link to original article PubMed
5. Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. link to original article PubMed

BACOP

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BACOP: Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone

Regimen

Study	Evidence	Comparator
Bajetta et al. 1988	Phase III	CVP

References

1. Bajetta E, Valagussa P, Bonadonna G, Lattuada A, Buzzoni R, Rilke F, Banfi A. Combined modality treatment for stage I-II non-Hodgkin's lymphomas: CVP versus BACOP chemotherapy. Int J Radiat Oncol Biol Phys. 1988 Jul;15(1):3-12. link to original article 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),

Regimen

Study	Evidence
Laurence et al. 1982	Phase II
Armitage et al. 1986	Phase II
Boyd et al. 1988	Phase II
Vose 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
4. Vose JM, Armitage JO, Weisenburger DD, Bierman PJ, Sorensen S, Hutchins M, Moravec DF, Howe D, Dowling MD, Mailliard J, et al. The importance of age in survival of patients treated with chemotherapy for aggressive non-Hodgkin's lymphoma. J Clin Oncol. 1988 Dec;6(12):1838-44. 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

Regimen

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

Regimen

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
Coiffier et al. 1986 (LNH-80)	Phase II

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
5. Coiffier B, Bryon PA, Berger F, Archimbaud E, Ffrench M, Extra JM, Guyotat D, Fiere D, Gentilhomme O, Magaud JP, et al. Intensive and sequential combination chemotherapy for aggressive malignant lymphomas (protocol LNH-80). J Clin Oncol. 1986 Feb;4(2):147-53. link to original article PubMed

C-MOPP

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

Regimen

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

Regimen

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	Comparator
Bagley et al. 1972	Phase II
Monfardini et al. 1977	Phase III	ABP
Bajetta et al. 1988	Phase III	BACOP

• 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
2. Monfardini S, Tancini G, DeLena M, Villa E, Valagussa P, Bonadonna G. Cyclophosphamide, vincristine, and prednisone (CVP) versus adriamycin, bleomycin, and prednisone (ABP) in stage IV non-Hodgkin's lymphomas. Med Pediatr Oncol. 1977;3(1):67-74. PubMed
3. Bajetta E, Valagussa P, Bonadonna G, Lattuada A, Buzzoni R, Rilke F, Banfi A. Combined modality treatment for stage I-II non-Hodgkin's lymphomas: CVP versus BACOP chemotherapy. Int J Radiat Oncol Biol Phys. 1988 Jul;15(1):3-12. 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

F-MACHOP

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F-MACHOP: Fluorouracil, Methotrexate, Ara-C (Cytarabine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study	Evidence
Amadori et al. 1985	Non-randomized

References

1. Amadori S, Guglielmi C, Anselmo AP, Cimino G, Ruco LP, Papa G, Biagini C, Mandelli F. Treatment of diffuse aggressive non-Hodgkin's lymphomas with an intensive multi-drug regimen including high-dose cytosine arabinoside (F-MACHOP). Semin Oncol. 1985 Jun;12(2 Suppl 3):218-22. PubMed
   1. Update: Guglielmi C, Amadori S, Anselmo AP, Baroni CD, Biagini C, Cimino G, Papa G, Mandelli F. Sequential combination chemotherapy of high-grade non-Hodgkin's lymphoma with 5-fluorouracil, methotrexate, cytosine-arabinoside, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP). Cancer Invest. 1987;5(3):159-69. PubMed
   2. Update: Guglielmi C, Amadori S, Ruco LP, Mantovani L, Martelli M, Papa G, Mandelli F. Combination chemotherapy for the treatment of diffuse aggressive lymphomas: F-MACHOP update. Semin Oncol. 1987 Jun;14(2 Suppl 1):104-9. PubMed
   3. Update: Guglielmi C, Amadori S, Martelli M, Dragoni F, Mandelli F. The F-MACHOP sequential combination chemotherapy regimen in advanced diffuse aggressive lymphomas: long-term results. Ann Oncol. 1991 May;2(5):365-71. link to original article PubMed
2. Infanti L, Silvestri F, Fanin R, Salmaso F, Zaja F, Barillari G, Patriarca F, Geromin A, Cerno M, Damiani D, Baccarani M. The F-MACHOP regimen in the treatment of aggressive non-Hodgkin's lymphomas: a single center experience in 72 patients. Haematologica. 1996 Nov-Dec;81(6):521-8. link to original article PubMed

HOP

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

Regimen

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

LD-ACOP-B

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LD-ACOP-B: Low-Dose Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone, Bleomycin

Regimen

Study	Evidence
O'Reilly et al. 1991	Non-randomized

References

1. O'Reilly SE, Klimo P, Connors JM. Low-dose ACOP-B and VABE: weekly chemotherapy for elderly patients with advanced-stage diffuse large-cell lymphoma. J Clin Oncol. 1991 May;9(5):741-7. link to original article PubMed

MACOP-B

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

Regimen

Study	Evidence	Comparator
Klimo et al. 1985	Non-randomized
Fisher et al. 1993 (SWOG-8516/Intergroup 0067)	Phase III	CHOP m-BACOD ProMACE-CytaBOM
Sertoli et al. 1994	Phase III	ProMACE-MOPP
Gianni et al. 1997	Phase III	High-dose sequential therapy

• 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
   1. Update: Klimo P, Connors JM. Updated clinical experience with MACOP-B. Semin Hematol. 1987 Apr;24(2 Suppl 1):26-34. 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
   1. Update: 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
   2. Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article PubMed
3. 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
4. Gianni AM, Bregni M, Siena S, Brambilla C, Di Nicola M, Lombardi F, Gandola L, Tarella C, Pileri A, Ravagnani F, Valagussa P, Bonadonna G. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med. 1997 May 1;336(18):1290-7. link to original article PubMed

m-BACOD

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m-BACOD: methotrexate (moderate dose), Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Dexamethasone

Structured Concept: C63458 (NCI-T), C1883662 (NCI-MT/UMLS)

Regimen

Study	Evidence	Comparator
Skarin et al. 1983	Non-randomized
Guglielmi et al. 1989	Phase III	m-BNCOD
Shipp et al. 1990	Non-randomized
Fisher et al. 1993 (SWOG-8516/Intergroup 0067)	Phase III	CHOP; MACOP-B; ProMACE-CytaBOM
Tilly et al. 2000 (LNH87-1)	Phase III	ACVBP

• Methotrexate (MTX) 200 mg/m2 IV once per day on days 8 & 15
• Bleomycin (Blenoxane) 4 units/m2 IV once on day 1
• Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
• Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
• Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
• Dexamethasone (Decadron) 6 mg/m2 (no route specified) once per day on days 1 to 5

Dose adjustments:

• If nadir WBC <1,000 or nadir platelets <50,000: 50% of cyclophosphamide and doxorubicin
• If WBC <1,000, platelets <50,000, or creatinine >50% of baseline on day of treatment, methotrexate was omitted

Supportive medications:

• Folinic acid (Leucovorin) 10 mg/m2 PO/IV Q6H x 8 doses, starting 24 hours after Methotrexate (MTX)

21-day cycle x 10 cycles

References

1. Skarin AT, Canellos GP, Rosenthal DS, Case DC Jr, MacIntyre JM, Pinkus GS, Moloney WC, Frei E 3rd. Improved prognosis of diffuse histiocytic and undifferentiated lymphoma by use of high dose methotrexate alternating with standard agents (M-BACOD). J Clin Oncol. 1983 Feb;1(2):91-8. link to original article PubMed
2. Guglielmi C, Gherlinzoni F, Amadori S, Mazza P, Mantovani L, Lauria F, Martelli M, Zinzani PL, Greco V, Poletti G, et al. A phase III comparative trial of m-BACOD vs m-BNCOD in the treatment of stage II-IV diffuse non-Hodgkin's lymphomas. Haematologica. 1989 Nov-Dec;74(6):563-9. PubMed
3. Shipp MA, Yeap BY, Harrington DP, Klatt MM, Pinkus GS, Jochelson MS, Rosenthal DS, Skarin AT, Canellos GP. The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen. J Clin Oncol. 1990 Jan;8(1):84-93. link to original article contains verified protocol PubMed
4. 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
   1. Update: 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
   2. Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article PubMed
5. Tilly H, Mounier N, Lederlin P, Brière J, Dupriez B, Sebban C, Bosly A, Biron P, Nouvel C, Herbrecht R, Bordessoule D, Coiffier B. Randomized comparison of ACVBP and m-BACOD in the treatment of patients with low-risk aggressive lymphoma: the LNH87-1 study. Groupe d'Etudes des Lymphomes de l'Adulte. J Clin Oncol. 2000 Mar;18(6):1309-15. link to original article PubMed

m-BNCOD

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m-BNCOD: methotrexate (moderate dose), Bleomycin, Novantrone (Mitoxantrone), Cyclophosphamide, Oncovin (Vincristine), Dexamethasone

Regimen

Study	Evidence	Comparator
Guglielmi et al. 1989	Phase III	m-BACOD

References

1. Guglielmi C, Gherlinzoni F, Amadori S, Mazza P, Mantovani L, Lauria F, Martelli M, Zinzani PL, Greco V, Poletti G, et al. A phase III comparative trial of m-BACOD vs m-BNCOD in the treatment of stage II-IV diffuse non-Hodgkin's lymphomas. Haematologica. 1989 Nov-Dec;74(6):563-9. PubMed

P/DOCE

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P/DOCE: Prednisone, Doxorubicin, Oncovin (Vincristine), Cyclophosphamide, Etoposide,

Regimen

Study	Evidence
O'Reilly et al. 1993	Phase II

Note that although the drugs are the same as those used in CHOEP, the doses are significantly different and this is intended for elderly persons (65+ years of age).

• Prednisone (Sterapred) 50 mg/day PO on days 1 to 10, 28 to 37, 49 to 58
• Doxorubicin (Adriamycin) 40 mg/m2 IV once per week on weeks 1, 2, 7, 8
• Vincristine (Oncovin) 1.2 mg/m2 IV once per day on days 1, 28, 49
• Cyclophosphamide (Cytoxan) 300 mg/m2 IV once per day on days 1, 28, 49
• Etoposide (Vepesid) 50 mg/m2 IV once on day 28, then 100 mg/m2 PO once per day on days 29 to 32

8-week course

References

1. O'Reilly SE, Connors JM, Howdle S, Hoskins P, Klasa R, Klimo P, Stuart DS. In search of an optimal regimen for elderly patients with advanced-stage diffuse large-cell lymphoma: results of a phase II study of P/DOCE chemotherapy. J Clin Oncol. 1993 Nov;11(11):2250-7. link to original article contains verified protocol 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

ProMACE-CytaBOM

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ProMACE-CytaBOM: Prolix (Prednisone), Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Cytarabine, Bleomycin, Oncovin (Vincristine), Methotrexate

Structured Concept: C63460 (NCI-T), C1882461 (NCI-MT/UMLS)

Regimen

Study	Evidence	Comparator
Longo et al. 1991	Phase III	ProMACE-MOPP
Fisher et al. 1993 (SWOG-8516/Intergroup 0067)	Phase III	CHOP; MACOP-B; m-BACOD

• Prednisone (Prolix) 60 mg/m2 PO once per day on days 1 to 14
• Methotrexate (MTX) 120 mg/m2 IV once on day 8
• Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
• Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
• Etoposide (Vepesid) 120 mg/m2 IV once on day 1
• Cytarabine (Cytosar) 300 mg/m2 IV once on day 8
• Bleomycin (Blenoxane) 5 units/m2 IV once on day 8
• Vincristine (Oncovin) 1.4 mg/m2 IV once on day 8

Supportive medications:

• Folinic acid (Leucovorin) 25 mg/m2 PO Q6H x 4 doses, starting 24 hours after Methotrexate (MTX)
• Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO BID throughout the course of treatment

Dose adjustments:

• "If WBC is =4,000, use 100% doses of all drugs
• If WBC count is 3,000 to 3,999, 100% prednisone, bleomycin, vincristine, cytarabine, and methotrexate; 75% cyclophosphamide, Adriamycin, and etoposide
• If WBC count is 2,000 to 2,999, 100% prednisone, bleomycin, vincristine, and methotrexate; 75% etoposide, cytarabine; 50% cyclophosphamide, Adriamycin
• If WBC count is 1,000 to 1,999, 100% prednisone, bleomycin, vincristine and methotrexate; 25% cyclophosphamide, Adriamycin, etoposide, and cytarabine
• If WBC count is 0 to 999, 100% prednisone, vincristine, and bleomycin; 50% methotrexate, no other drugs
• If platelet count is =100,000, use 100% doses of all drugs
• If platelet count is 50,000 to 99,000, 100% prednisone, bleomycin, vincristine, and methotrexate; 50% etoposide and cytarabine; 25% cyclophosphamide and Adriamycin
• If platelet count is 0 to 49,000, 100% prednisone, bleomycin, and vincristine; 50% methotrexate, no other drugs"

21-day cycle x 6 cycles or 2 cycles after maximum clinical response

• Patients with initial bone or bone marrow involvement who achieved a CR were treated with 2,400 cGy prophylactic cranial irradiation.

References

1. Longo DL, DeVita VT Jr, Duffey PL, Wesley MN, Ihde DC, Hubbard SM, Gilliom M, Jaffe ES, Cossman J, Fisher RI et al. Superiority of ProMACE-CytaBOM over ProMACE-MOPP in the treatment of advanced diffuse aggressive lymphoma: results of a prospective randomized trial. J Clin Oncol. 1991 Jan;9(1):25-38. Erratum in: J Clin Oncol 1991 Apr;9(4):710. link to original article contains verified protocol 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
   1. Update: 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
   2. Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article PubMed

ProMACE-MOPP

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ProMACE-MOPP: Prolix (Prednisone), Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Mustargen (Mechlorethamine), Oncovin (Vincristine), Procarbazine, Prednisone

Regimen

Study	Evidence	Comparator
Longo et al. 1991	Phase III	ProMACE-CytaBOM
Sertoli et al. 1994	Phase III	MACOP-B

References

1. Longo DL, DeVita VT Jr, Duffey PL, Wesley MN, Ihde DC, Hubbard SM, Gilliom M, Jaffe ES, Cossman J, Fisher RI et al. Superiority of ProMACE-CytaBOM over ProMACE-MOPP in the treatment of advanced diffuse aggressive lymphoma: results of a prospective randomized trial. J Clin Oncol. 1991 Jan;9(1):25-38. Erratum in: J Clin Oncol 1991 Apr;9(4):710. link to original article PubMed
2. 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

VABE

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VABE: Vincristine, Adriamycin (Doxorubicin), Bleomycin, Etoposide, Prednisone

Regimen

Study	Evidence
O'Reilly et al. 1991	Non-randomized

References

1. O'Reilly SE, Klimo P, Connors JM. Low-dose ACOP-B and VABE: weekly chemotherapy for elderly patients with advanced-stage diffuse large-cell lymphoma. J Clin Oncol. 1991 May;9(5):741-7. link to original article PubMed

VACOP-B; P-VABEC

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VACOP-B: Vepesid (Etoposide), Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone, Bleomycin
P-VABEC: Prednisone, Vincristine, Adriamycin (Doxorubicin), Bleomycin, Etoposide, Cyclophosphamide

Regimen

Study	Evidence
Pichert et al. 1992	Retrospective
Martelli et al. 1993	Phase II

References

1. Conner JM, Hoskins P, Klasa R et al. VACOP-B: 12-week chemotherapy for advanced stage diffuse large cell lymphoma. Efficacy is sustained and toxicity reduced compared to MACOP-B. Proc Amer Soc Clin Oncol 1990; 9: 254.
2. Pichert G, Peters J, Stahel RA, Dommann C, Joss R, Gebbers JO, Kroner T, Sulser H, Honegger HP, Maurer R, et al. Chemotherapy with MACOP-B and VACOP-B for intermediate- and high-grade non-Hodgkin's lymphoma: clinical results and analysis of prognostic factors. Ann Oncol. 1992 Sep;3(8):645-9. link to original article PubMed
3. Martelli M, Guglielmi C, Coluzzi S, Avvisati G, Amadori S, Giovannini M, Torromeo C, Mandelli F. P-VABEC: a prospective study of a new weekly chemotherapy regimen for elderly aggressive non-Hodgkin's lymphoma. J Clin Oncol. 1993 Dec;11(12):2362-9. 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

GDP

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GDP: Gemcitabine, Dexamethasone, Platinol (Cisplatin)

Regimen

Study	Evidence
Crump et al. 2004	Phase II

• Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
• Dexamethasone (Decadron) 40 mg PO/IV once per day on days 1 to 4
• Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1

21-day cycle x up to 6 cycles

References

1. Crump M, Baetz T, Couban S, Belch A, Marcellus D, Howson-Jan K, Imrie K, Myers R, Adams G, Ding K, Paul N, Shepherd L, Iglesias J, Meyer R. Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Cancer. 2004 Oct 15;101(8):1835-42. link to original article PubMed

IMVP-16

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IMVP-16: Ifosfamide, Methotrexate, VP-16 (Etoposide)

Regimen

Study	Evidence
Cabanillas et al. 1982	Phase II

• Ifosfamide (Ifex)
• Methotrexate (MTX)
• Etoposide (Vepesid)

References

1. Cabanillas F, Hagemeister FB, Bodey GP, Freireich EJ. IMVP-16: an effective regimen for patients with lymphoma who have relapsed after initial combination chemotherapy. Blood. 1982 Sep;60(3):693-7. link to original article PubMed

MINE-ESHAP

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MINE: Mesna, Ifosfamide, Novantrone (Mitoxantrone), Etoposide
ESHAP: Etoposide, High dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study	Evidence
Rodriguez et al. 1995	Phase II

Part 1: MINE

• Ifosfamide (Ifex) 1.33 g/m2 IV over 1 hour once per day on days 1 to 3
• Mitoxantrone (Novantrone) 8 g/m2 IV once on day 1
• Etoposide (Vepesid) 65 mg/m2 IV over 1 hour once per day on days 1 to 3

Supportive medications:

• Mesna (Mesnex) 1.33 g/m2 IV over 1 hour once per day on days 1 to 3
• Mesna (Mesnex) 500 mg PO once, diluted in water or juice, 4 hours following ifosfamide administration

Part 2: ESHAP

• Etoposide (Vepesid) 60 mg/m2 IV over 1 hour once per day on days 1 to 4
• Methylprednisolone (Solumedrol) 500 mg IV as a short infusion once per day on days 1 to 4
• Cytarabine (Cytosar) 2000 mg/m2 IV over 2 hours once on day 5
• Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion over 96 hours (total dose per cycle: 100 mg/m2) on days 1 to 4

21-day cycles; patients who achieved a CR received a total of 6 cycles of MINE and then 3 cycles of ESHAP as consolidation therapy. If patients achieved a PR, then MINE was given to the point of maximal response, and then patients were crossed over to ESHAP.

References

1. Rodriguez MA, Cabanillas FC, Velasquez W, Hagemeister FB, McLaughlin P, Swan F, Romaguera JE. Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP. J Clin Oncol. 1995 Jul;13(7):1734-41. link to original article contains verified protocol PubMed

NOAC

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NOAC: NOvantrone (Mitoxantrone), Ara-C (Cytarabine)

Regimen

Study	Evidence
Ho et al. 1989	Phase II

References

1. Ho AD, del Valle F, Rückle H, Schwammborn J, Schlimok G, Hiddemann W, Meusers P, Thiel E, Dörken B, Hunstein W. Mitoxantrone and high-dose cytarabine as salvage therapy for refractory non-Hodgkin's lymphoma. Cancer. 1989 Oct 1;64(7):1388-92. PubMed

VIM

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VIM: Vepesid (Etoposide), Ifosfamide, Mitoxantrone

Regimen

Study	Evidence
Hopfinger et al. 1995	Phase II

References

1. Hopfinger G, Heinz R, Koller E, Schneider B, Pittermann E. Ifosfamide, mitoxantrone and etoposide (VIM) as salvage therapy of low toxicity in non-Hodgkin's lymphoma. Eur J Haematol. 1995 Oct;55(4):223-7. PubMed