Diffuse large B-cell lymphoma - historical
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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. Is there a regimen missing from this list? See the main DLBCL page for current regimens.
67 regimens on this page
86 variants on this page
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Untreated
ABP
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ABP: Adriamycin (Doxorubicin), Bleomycin, Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Monfardini et al. 1977 | 1972-1974 | Phase III (E-switch-ic) | CVP | Seems not superior |
Chemotherapy
References
- 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. link to original article PubMed
ACE
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ACE: Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Dumontet et al. 2000 | 1995-1998 | Phase II | ||
Haioun et al. 2009 (LNH 98-3) | 1999-2004 | Phase III (E-de-esc) | ACVBP | Seems not superior |
Chemotherapy
- Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day on days 1 & 2
- Etoposide (Vepesid) as follows:
- Cycles 2 to 4: 150 mg/m2 IV once per day on days 1 to 3
- Prednisone (Sterapred) 60 mg/m2 (route not specified) once per day on days 1 to 5
CNS prophylaxis
- Methotrexate (MTX) 15 mg IT once on day 2
Supportive medications
- G-CSF 5 mcg/kg/day SC on days 6 to 13
References
- 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. link to original article PubMed
- LNH 98-3: 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 contains verified protocol PubMed
ACOMLA
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ACOMLA: Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Methotrexate, Leucovorin (Folinic acid), Ara-C (Cytarabine)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Newcomer et al. 1982 | NR in abstract | Randomized, <20 patients | CHOP-B | Seems to have inferior RFS |
Chemotherapy
- Doxorubicin (Adriamycin)
- Cyclophosphamide (Cytoxan)
- Vincristine (Oncovin)
- Methotrexate (MTX)
- Cytarabine (Ara-C)
References
- 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
Protocol
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tilly et al. 2000 (LNH87-1) | 1987-1993 | Phase III (E-esc) | m-BACOD | Seems not superior |
Tilly et al. 2003 | 1993-1998 | Phase III (E-esc) | CHOP | Seems to have superior OS |
Morel et al. 2010 (LNH93-2) | 1993-1998 | Phase III (C) | ECVBP | Did not meet primary endpoint of EFS |
Reyes et al. 2005 (LNH 93-01) | 1993-2000 | Phase III (E-esc) | CHOP, then RT | Superior OS |
Haioun et al. 2009 (LNH 98-3) | 1999-2004 | Phase III (C) | ACE | Seems not superior |
Ketterer et al. 2013 (LNH03-1B) | 2003-2008 | Phase III (C) | R-ACVBP | Seems to have inferior PFS |
Chemotherapy, induction
- 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 IT on day 2
Supportive medications
- G-CSF or GM-CSF SC once per day on days 6 to 13
21-day cycle for 4 cycles, followed by:
Chemotherapy, consolidation, part 1
- Methotrexate (MTX) 3000 mg/m2 IV once on day 1
Supportive medications
- Leucovorin rescue
14-day cycle for 2 cycles, followed by:
Chemotherapy, consolidation, 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 for 4 cycles, beginning 2 weeks after completion of MTX, then
Chemotherapy, consolidation, part 3
- Cytarabine (Ara-C) 100 mg/m2 SC once per day on days 1 to 4
14-day cycle for 2 cycles, beginning 2 weeks after completion of EI
References
- LNH87-1: Tilly H, Mounier N, Lederlin P, Brière J, Dupriez B, Sebban C, Bosly A, Biron P, Nouvel C, Herbrecht R, Bordessoule D, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte. Randomized comparison of ACVBP and m-BACOD in the treatment of patients with low-risk aggressive lymphoma: the LNH87-1 study. J Clin Oncol. 2000 Mar;18(6):1309-15. link to original article PubMed
- 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
- LNH 93-01: 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. 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
- LNH 98-3: 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
- LNH93-2: Morel P, Munck JN, Coiffier B, Gisselbrecht C, Ranta D, Bosly A, Tilly H, Quesnel B, Thyss A, Mounier N, Brière J, Molina T, Reyes F; GELA. Comparison of two high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone derived regimens in patients aged under 60 years with low-intermediate risk aggressive lymphoma: a final analysis of the multicenter LNH93-2 protocol. Leuk Lymphoma. 2010 Sep;51(9):1668-77. link to original article PubMed
- LNH03-1B: 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; GELA. 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
ACVBP (Methylprednisolone)
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ACVBP: Adriamycin (Doxorubicin), Cyclophosphamide, Vindesine, Bleomycin, MethylPrednisone
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Coiffier et al. 1986 (LNH-80) | 1980-1984 | Phase II |
Note: this regimen is referred to as "intensified CHOP-Bleo" in the original manuscript, but bears more resemblance to ACVBP induction and is therefore re-named as ACVBP.
Chemotherapy
- 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) 5 mg/m2 IV once per day on days 1 to 5
- Methylprednisolone (Solumedrol) 60 mg/m2 (route not specified) once per day on days 1 to 5
CNS prophylaxis
- Methotrexate (MTX) 15 mg IT once
15-day cycle for 3 cycles; cycles were delayed until ANC greater than 1500/uL
Subsequent treatment
- Cytarabine & Methotrexate (CYM), then CVAP-Bleo
References
- LNH-80: Coiffier B, Bryon PA, Berger F, Archimbaud E, Ffrench M, Extra JM, Guyotat D, Fiere D, Gentilhomme O, Magaud JP, Blanc M, Peaud PY, Vuvan H, Viala JJ. 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 contains verified protocol PubMed
BCOP
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BCOP: BCNU (Carmustine), Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gams et al. 1985 | 1977-1981 | Phase III (E-switch-ic) | CHOP | Might have inferior OS |
Chemotherapy
- Carmustine (BCNU) 100 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg/m2 IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
28-day cycle for 6 cycles
References
- Gams RA, Rainey M, Dandy M, Bartolucci AA, Silberman H, Omura G; Southeastern Cancer Study Group. Phase III study of BCOP v CHOP in unfavorable categories of malignant lymphoma: a Southeastern Cancer Study Group trial. J Clin Oncol. 1985 Sep;3(9):1188-95. link to original article contains verified protocol PubMed
CAP-BOP
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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 |
Chemotherapy
- Cyclophosphamide (Cytoxan)
- Doxorubicin (Adriamycin)
- Procarbazine (Matulane)
- Bleomycin (Blenoxane)
- Vincristine (Oncovin)
- Prednisone (Sterapred)
References
- 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
- Armitage JO, Weisenburger DD, Hutchins M, Moravec DF, Dowling M, Sorensen S, Mailliard J, Okerbloom J, Johnson PS, Howe D, Bascom GK, Casey J, Linder J, Purtilo DT. 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
- Boyd DB, Coleman M, Papish SW, Topilow A, Kopel SK, Bernhardt B, Files JC, Schwartz S, Gaynor M, McDermott D, Reisman AM, Coleman BL. COPBLAM III: infusional combination chemotherapy for diffuse large-cell lymphoma. J Clin Oncol. 1988 Mar;6(3):425-33. link to original article PubMed
- Vose JM, Armitage JO, Weisenburger DD, Bierman PJ, Sorensen S, Hutchins M, Moravec DF, Howe D, Dowling MD, Mailliard J, Johnson PS, Pevnick W, Packard WM, Okerbloom J, Thompson RF, Langdon RM Jr, Soori G, Peterson C. 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 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 30 minutes once on day 1
- Pegylated liposomal doxorubicin (Doxil) 30 mg/m2 IV over 60 minutes once on day 1
- Vincristine (Oncovin) 2 mg IV over 15 minutes once on day 1
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
21-day cycle for 6 to 8 cycles
References
- 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
CEEP
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CEEP: Cyclophosphamide, Epirubicin, Eldesine (Vindesine), Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Milpied et al. 2004 (GOELAMS 072) | 1994-1999 | Phase III (E-esc) | CHOP | Seems to have superior EFS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
- Epirubicin (Ellence) 100 mg/m2 IV once on day 1
- Vindesine (Eldisine) 3 mg/m2 IV once on day 1
- Prednisone (Sterapred) 80 mg/m2 PO or IV once per day on days 1 to 5
CNS prophylaxis
- Methotrexate (MTX) 15 mg IT once on day 2
- Methylprednisolone (Solumedrol) IT once on day 2
2 cycles
Subsequent treatment
- Patients with at least PR: CYM, then BEAM with auto HSCT
References
- GOELAMS 072: Milpied N, Deconinck E, Gaillard F, Delwail V, Foussard C, Berthou C, Gressin R, Lucas V, Colombat P, Harousseau JL; Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004 Mar 25;350(13):1287-95. link to original article contains verified protocol PubMed
CEOP
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CEOP: Cyclophosphamide, Epirubicin, Oncovin (Vincristine), Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Economopoulos et al. 2002 | 1993-1999 | Phase III (C) | CNOP | Did not meet efficacy endpoints |
Chamorey et al. 2005 | 1994-1998 | Phase III (C) | MEMID | Did not meet primary endpoint of OS |
Economopoulos et al. 2007 (HE22A99) | 1999-2005 | Phase III (C) | CEOP-14 | Did not meet primary endpoint of OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Epirubicin (Ellence) 70 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Prednisone (Sterapred) 60 mg PO once per day on days 1 to 7
21-day cycles
References
- Economopoulos T, Dimopoulos MA, Mellou S, Pavlidis N, Samantas E, Nicolaides C, Tsatalas C, Papadopoulos A, Papageogriou E, Papasavvas P, Fountzilas G. Treatment of intermediate- and high-grade non-Hodgkin's lymphoma using CEOP versus CNOP. Eur J Haematol. 2002 Mar;68(3):135-43. link to original article contains verified protocol PubMed
- Chamorey E, Gressin R, Peyrade F, Rossi JF, Lepeu G, Foussard C, Harrousseau JL, Fabbro M, Richard B, Delwail V, Maisonneuve H, Vilque JP, Thyss A. Prospective randomized study comparing MEMID with a chop-like regimen in elderly patients with aggressive non-Hodgkin's lymphoma. Oncology. 2005;69(1):19-26. Epub 2005 Jul 28. link to original article PubMed
- HE22A99: Economopoulos T, Psyrri A, Dimopoulos MA, Kalogera-Fountzila A, Pavlidis N, Tsatalas C, Nikolaides C, Mellou S, Xiros N, Fountzilas G; Hellenic Cooperative Oncology Group. CEOP-21 versus CEOP-14 chemotherapy with or without rituximab for the first-line treatment of patients with aggressive lymphomas: results of the HE22A99 trial of the Hellenic Cooperative Oncology Group. Cancer J. 2007 Sep-Oct;13(5):327-34. link to original article PubMed
CEOP (Prednisolone)
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CEOP: Cyclophosphamide, Epirubicin, Oncovin (Vincristine), Prednisolone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hertzberg et al. 2014 (ALLG NHL07) | 1994-1999 | Phase III (C) | DI-CEOP | Did not meet primary endpoint of OS60 |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Epirubicin (Ellence) 75 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
- Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
21-day cycle for 6 cycles
References
- ALLG NHL07: Hertzberg M, Matthews JP, Stone JM, Dubosq MC, Grigg A, Ellis D, Benson W, Browett P, Horvath N, Januszewicz H, Abdi E, Green M, Bonaventura A, Marlton P, Cannell P, Wolf M; ALLG. A phase III randomized trial of high-dose CEOP + filgrastim versus standard-dose CEOP in patients with non-Hodgkin lymphoma: 10-year follow-up data: Australasian Leukaemia and Lymphoma Group (ALLG) NHL07 trial. Am J Hematol. 2014 May;89(5):536-41. Epub 2014 Feb 21. link to original article contains protocol PubMed
CHOEP-14
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CHOEP-14: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 14 days
CHOPE: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne, Etoposide
VACOP: Vepesid (Etoposide), Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Pfreundschuh et al. 2004 (NHL-B1) | 1993-2000 | Phase III (E-esc) | 1. CHOP-21 2. CHOP-14 |
Superior EFS | Seems more toxic |
3. CHOEP-21 | Seems to have superior OS | ||||
Pfreundschuh et al. 2004 (NHL-B2) | 1993-2000 | Phase III (E-esc) | 1. CHOEP-21 2. CHOP-21 3. CHOP-14 |
Seems not superior | Seems more toxic |
Chemotherapy
- 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
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications
- Filgrastim (Neupogen) as follows:
- Patients less than 75 kg: 300 mcg SC once per day on days 4 to 13
- Patients at least 75 kg: 480 mcg SC once per day on days 4 to 13
14-day cycle for 6 cycles, next cycle to start as long as WBC count is greater than 2.5 x 109/L and platelets greater than 80 x 109/L
Subsequent treatment
- Some protocols: Patients with initial bulky disease (mass conglomerate at least 7.5 cm) received 36 Gy radiation therapy to extranodal sites of disease when possible
References
- NHL-B1: 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
- NHL-B2: 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
- Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains verified protocol PubMed
- Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial Group. Lancet Oncol. 2011 Oct;12(11):1013-22. link to original article contains protocol PubMed
CHOEP-21
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CHOEP-21: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 21 days
CHOPE: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne, Etoposide
VACOP: Vepesid (Etoposide), Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Köppler et al. 1991 | NR | Phase III (C) | hCHOP alternating with IVEP | ||
Kaiser et al. 2002 | 1990-1997 | Phase III (C) | CHOEP, then BEAM with auto HSCT | Seems not superior | |
Pfreundschuh et al. 2004 (NHL-B1) | 1993-2000 | Phase III (E-esc) | 1. CHOP-21 2. CHOP-14 |
Superior EFS | Seems more toxic |
3. CHOEP-14 | Seems to have inferior OS | ||||
Pfreundschuh et al. 2004 (NHL-B2) | 1993-2000 | Phase III (E-esc) | 1. CHOEP-14 2. CHOP-21 3. CHOP-14 |
Seems not superior | Seems more toxic |
Chemotherapy
- 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
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications
- Filgrastim (Neupogen) by discretion of ordering physician
21-day cycle for 4 to 6 cycles, next cycle to start as long as WBC is >2.5 and platelets >80
Subsequent treatment
- Some protocols: Patients with initial bulky disease (mass conglomerate at least 7.5 cm) received 36 Gy radiation therapy to extranodal sites of disease when possible
References
- Köppler H, Pflüger KH, Eschenbach I, Pfab R, Birkmann J, Zeller W, Steinhauer EU, Gropp C, Oehl S, Lötzke E, Kuhn H, Drings P, Gossmann HH, Lennert K, Stein H, Havemann K. 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. link to original article PubMed
- Kaiser U, Uebelacker I, Abel U, Birkmann J, Trümper L, Schmalenberg H, Karakas T, Metzner B, Hossfeld DK, Bischoff HG, Franke A, Reiser M, Müller P, Mantovani L, Grundeis M, Rothmann F, von Seydewitz CU, Mesters RM, Steinhauer EU, Krahl D, Schumacher K, Kneba M, Baudis M, Schmitz N, Pfab R, Köppler H, Parwaresch R, Pfreundschuh M, Havemann K. Randomized study to evaluate the use of high-dose therapy as part of primary treatment for "aggressive" lymphoma. J Clin Oncol. 2002 Nov 15;20(22):4413-9. link to original article PubMed
- NHL-B1: 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
- NHL-B2: 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
- Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains verified protocol PubMed
- Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. link to original article contains protocol PubMed
CHOP
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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen variant #1, 3 cycles, prednisone 40 mg/m2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Link et al. 1990 | 1983-1987 | Phase III (Ede-esc) | CHOP & RT | Seems not superior |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Note some substantial differences from typical CHOP protocols.
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.5 mg/m2 IV once on day 1
- Prednisone (Sterapred) as follows:
- Cycle 1: 40 mg/m2 PO once per day on days 1 to 21
- Cycle 2: 40 mg/m2 PO once per day on days 1 to 7
- Cycle 3: 40 mg/m2 PO once per day on days 1 to 5
21-day cycle for 3 cycles
Subsequent treatment
- 6-MP & MTX maintenance
Regimen variant #2, 3 cycles, prednisone 100 mg
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Miller et al. 1998 (SWOG S8736) | 1988-1995 | Phase III (E-switch-ooc) | See link | See link |
Reyes et al. 2005 (LNH 93-01) | 1993-2000 | Phase III (C) | ACVBP | Inferior OS |
Persky et al. 2014 (SWOG S0313) | 2004-2008 | Phase II |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV over 1 to 2 minutes once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV over 1 to 2 minutes once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 3 cycles
Subsequent treatment
- SWOG S0313: IFRT, then ibritumomab tiuxetan consolidation
- Others (see papers): Involved field radiation therapy, 180 to 200 cGy fractions, total dose of 4000 to 5500 cGy. Total dose was often influenced by whether patients had clinical evidence of residual disease after 4000 cGy.
Regimen variant #3, 4 cycles
Study | Evidence |
---|---|
Tondini et al. 1993 | Phase II |
Bonnet et al. 2007 | Non-randomized portion of RCT |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
21-day cycle for 4 cycles
Subsequent treatment
- IFRT x 40 Gy versus no further treatment
Regimen variant #4, 6 cycles, 100 mg prednisone
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pfreundschuh et al. 2004 (NHL-B1) | 1993-2000 | Phase III (C) | 1. CHOEP-14 2. CHOP-14 |
Seems to have inferior OS |
3. CHOEP-21 | Inferior EFS | |||
Pfreundschuh et al. 2004 (NHL-B2) | 1993-2000 | Phase III (C) | 1. CHOEP-14 | Seems not superior |
2. CHOEP-21 | Seems not superior | |||
3. CHOP-14 | Inferior OS | |||
Verdonck et al. 2007 (HOVON-26) | 1994-2004 | Phase III (C) | I-CHOP | Seems not superior |
Fridrik et al. 2009 (AGMT NHL-5) | 1995-2001 | Phase III (C) | CEOP/IMVP-Dexa | Inferior OS |
Preceding treatment
- NHL-B1 and NHL-B2: Pre-phase vincristine & prednisone
Chemotherapy
- 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
Supportive medications
- Per NHL-B1 and NHL-B2: At the discretion of ordering physician: 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
21-day cycle for 6 cycles
Subsequent treatment
- NHL-B2, patients with "lymphoma masses or conglomerates with a diameter ≥7.5 cm) or extranodal involvement": RT x 36 Gy to areas of initial bulky disease
Regimen variant #5, 6 cycles, 50 mg/m2 prednisone
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sonneveld et al. 1995 | 1988-1993 | Phase III (C) | CNOP | Seems to have superior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 50 mg/m2 PO once per day on days 1 to 5
28-day cycle for 6 cycles
Regimen variant #6, 6 to 8 cycles
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zinzani et al. 1995 | 1991-1993 | Phase III (C) | CIOP | Did not meet efficacy endpoints |
Habermann et al. 2006 (ECOG E4494) | 1998-2001 | Phase III (C) | R-CHOP | Seems to have inferior FFS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
Supportive medications
- Filgrastim (Neupogen) "recommended according to guidelines"
21-day cycle for 6 to 8 cycles
Subsequent treatment
- ECOG E4494, patients with CR/PR: Maintenance rituximab versus observation
Regimen variant #7, 8 cycles, 40 mg/m2 prednisone
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tilly et al. 2003 | 1993-1998 | Phase III (C) | ACVBP | Seems to have inferior OS |
Coiffier et al. 2002 (LNH 98-5) | 1998-2000 | Phase III (C) | R-CHOP | Inferior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
Supportive medications
- Filgrastim (Neupogen) used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
21-day cycle for 8 cycles
Regimen variant #8, 8 cycles, 100 mg prednisone
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
McKelvey et al. 1976 | 1972-1974 | Phase III (E-esc) | HOP | Seems not superior |
Elias et al. 1978 | 1974-1977 | Non-randomized | ||
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) | 1986-1991 | Phase III (C) | 1. MACOP-B | Did not meet endpoint of OS |
2. m-BACOD | Did not meet endpoint of OS | |||
3. ProMACE-CytaBOM | Did not meet endpoint of OS | |||
Verdonck et al. 1995 | 1987-1994 | Phase III (C) | CHOP x 3, then HDT with auto HSCT | Seems not superior |
Miller et al. 1998 (SWOG S8736) | 1988-1995 | Phase III (C) | CHOP x 3, then RT | Seems to have inferior OS |
Jerkeman et al. 1999 | 1989-1994 | Phase III (C) | MACOP-B | Seems not superior |
Betticher et al. 2006 (MISTRAL) | 1997-2003 | Phase III (C) | SHiDo | Seems not superior |
Ohmachi et al. 2010 (JCOG 9809) | 1999-2002 | Phase III (C) | CHOP-14 | Seems not superior |
Note: McKelvey et al. 1976 gave CHOP for 3 cycles past CR.
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV over 1 to 2 minutes once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV over 1 to 2 minutes once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 8 cycles
Regimen variant #9, 8 cycles, uncapped vincristine, 100 mg prednisone
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gams et al. 1985 | 1977-1981 | Phase III (E-switch-ic) | BCOP | Might have superior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg/m2 IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 8 cycles
Regimen variant #10, 8 cycles, uncapped vincristine, 100 mg/m2 prednisone
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Milpied et al. 2004 (GOELAMS 072) | 1994-1999 | Phase III (C) | CEEP, then CYM, then BEAM with auto HSCT | Seems to have inferior EFS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycle for 8 cycles
Regimen variant #11, other
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Andersen et al. 1990 | 1983-1985 | Phase III (C) | CisEBP | Superior CR rate |
Chemotherapy
References
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- Elias L, Portlock CS, Rosenberg SA. Combination chemotherapy of diffuse histiocytic lymphoma with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). Cancer. 1978 Oct;42(4):1705-10. link to original article contains verified protocol PubMed
- Gams RA, Rainey M, Dandy M, Bartolucci AA, Silberman H, Omura G; Southeastern Cancer Study Group. Phase III study of BCOP v CHOP in unfavorable categories of malignant lymphoma: a Southeastern Cancer Study Group trial. J Clin Oncol. 1985 Sep;3(9):1188-95. link to original article PubMed
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- Sonneveld P, de Ridder M, van der Lelie H, Nieuwenhuis K, Schouten H, Mulder A, van Reijswoud I, Hop W, Lowenberg B. Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin's lymphoma using CHOP versus CNOP chemotherapy. J Clin Oncol. 1995 Oct;13(10):2530-9. link to original article contains verified protocol PubMed
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- LNH 98-5: Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C; Groupe d'Etude des Lymphomes de l'Adulte. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. link to original article contains verified protocol PubMed
- Update: 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 PubMed
- Update: Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. link to original article contains verified protocol PubMed
- Update: Mounier N, Heutte N, Thieblemont C, Briere J, Gaulard P, Feugier P, Ghesquieres H, Van Den Neste E, Robu D, Tilly H, Bouabdallah R, Safar V, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte. Ten-year relative survival and causes of death in elderly patients treated with R-CHOP or CHOP in the GELA LNH-985 trial. Clin Lymphoma Myeloma Leuk. 2012 Jun;12(3):151-4. Epub 2012 Feb 1. link to original article PubMed
- 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
- NHL-B1: 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
- NHL-B2: 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
- GOELAMS 072: Milpied N, Deconinck E, Gaillard F, Delwail V, Foussard C, Berthou C, Gressin R, Lucas V, Colombat P, Harousseau JL; Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004 Mar 25;350(13):1287-95. link to original article contains verified protocol PubMed
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- LNH 93-01: 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. 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
- Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains verified protocol PubMed
- Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. link to original article contains protocol PubMed
- ECOG E4494: Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. link to original article contains verified protocol PubMed NCT00003150
- MISTRAL: Betticher DC, Martinelli G, Radford JA, Kaufmann M, Dyer MJ, Kaiser U, Aulitzky WE, Beck J, von Rohr A, Kovascovics T, Cogliatti SB, Cina S, Maibach R, Cerny T, Linch DC. Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL). Ann Oncol. 2006 Oct;17(10):1546-52. Epub 2006 Aug 3. link to original article PubMed
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- AGMT NHL-5: Fridrik MA, Hausmaninger H, Lang A, Drach J, Krieger O, Geissler D, Michlmayr G, Ulsperger E, Chott A, Oberaigner W, Greil R. Dose-dense therapy improves survival in aggressive non-Hodgkin's lymphoma. Ann Hematol. 2010 Mar;89(3):273-82. Epub 2009 Aug 20. link to original article PubMed
- JCOG 9809: Ohmachi K, Tobinai K, Kobayashi Y, Itoh K, Nakata M, Shibata T, Morishima Y, Ogura M, Suzuki T, Ueda R, Aikawa K, Nakamura S, Fukuda H, Shimoyama M, Hotta T; Lymphoma Study Group of the Japan Clinical Oncology Group. Phase III trial of CHOP-21 versus CHOP-14 for aggressive non-Hodgkin's lymphoma: final results of the Japan Clinical Oncology Group Study, JCOG 9809. Ann Oncol. 2011 Jun;22(6):1382-91. Epub 2010 Dec 31. link to original article contains verified protocol PubMed NCT00133302
- SWOG S0313: Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. Epub 2014 Nov 13. link to original article contains verified protocol link to PMC article PubMed NCT00070018
CHOP-14
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CHOP-DI: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Dose Intense
I-CHOP: Intensified Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
CHOP-14: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone every 14 days
Regimen variant #1
Study | Evidence |
---|---|
Blayney et al. 2003 (SWOG 9349) | Phase II |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 65 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 11, or until ANC is greater than 10,000/uL
14-day cycle for up to 6 cycles
Regimen variant #2
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Verdonck et al. 2007 (HOVON-26) | 1994-2004 | Phase III (E-esc) | CHOP-21 | Seems not superior |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 70 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
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 11
14-day cycle for 6 cycles
Regimen variant #3
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pfreundschuh et al. 2004 (NHL-B1) | 1993-2000 | Phase III (E-esc) | 1. CHOEP-14 | Inferior EFS |
2. CHOEP-21 3. CHOP-21 |
Seems to have superior OS | |||
Pfreundschuh et al. 2008 (RICOVER-60) | 2000-2005 | Phase III (C) | 1. CHOP-14 x 8 | Seems to have inferior EFS |
2. R-CHOP-14 x 6 | Inferior OS | |||
3. R-CHOP-14 x 8 | Inferior PFS |
Preceding treatment
- Pre-phase vincristine & prednisone (recommended in NHL-B1 and mandatory in RICOVER-60)
Chemotherapy
- 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
Supportive medications
- (per Pfreundschuh et al. 2004):
- Filgrastim (Neupogen) 300 mcg (for patients less than 75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13
14-day cycle for 6 cycles
Subsequent treatment
- Patients with "Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter of at least 7.5 cm or extranodal involvement": RT, 36 Gy to areas of initial bulky disease
Regimen variant #4
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pfreundschuh et al. 2008 (RICOVER-60) | 2000-2005 | Phase III (C) | 1. CHOP-14 x 6 | Seems to have superior EFS |
2. R-CHOP-14 x 6 | Not reported | |||
3. R-CHOP-14 x 8 | Not reported |
Preceding treatment
Chemotherapy
- 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
Supportive medications
- Filgrastim (Neupogen) 300 mcg (for patients less than 75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13
14-day cycle for 8 cycles
Subsequent treatment
- Patients with "Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter of at least 7.5 cm or extranodal involvement": RT, 36 Gy to areas of initial bulky disease
References
- SWOG 9349: Blayney DW, LeBlanc ML, Grogan T, Gaynor ER, Chapman RA, Spiridonidis CH, Taylor SA, Bearman SI, Miller TP, Fisher RI; SWOG. Dose-intense chemotherapy every 2 weeks with dose-intense cyclophosphamide, doxorubicin, vincristine, and prednisone may improve survival in intermediate- and high-grade lymphoma: a phase II study of the Southwest Oncology Group (SWOG 9349). J Clin Oncol. 2003 Jul 1;21(13):2466-73. link to original article contains verified protocol PubMed
- NHL-B1: 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
- NHL-B2: 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 PubMed
- HOVON-26: Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. link to original article contains verified protocol PubMed
- RICOVER-60: Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. link to original article contains verified protocol PubMed NCT00052936
CHOP Modified
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mCHOP: modified Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence |
---|---|
Link et al. 1997 | Non-randomized portion of RCT |
This regimen has some major differences from standard CHOP.
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once per day on days 1, 22, 43
- Doxorubicin (Adriamycin) 40 mg/m2 IV once per day on days 1, 22, 43
- Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36, 43
- Prednisone (Sterapred) 40 mg/m2/day on days 1 to 28, 43 to 47
9-week course
References
- Link MP, Shuster JJ, Donaldson SS, Berard CW, Murphy SB. Treatment of children and young adults with early-stage non-Hodgkin's lymphoma. N Engl J Med. 1997 Oct 30;337(18):1259-66. link to original article PubMed
CHOP Modified (Prednisolone)
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mCHOP: modified Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bessell et al. 2003 (CLG NH 3003) | 1993-2000 | Phase III (E-switch-ic) | MCOP | Seems not superior |
This regimen is designed for elderly patients and is of lower intensity than standard CHOP.
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg IV once on day 1
- Prednisolone (Millipred) 20 mg PO twice per day on days 1 to 5
21-day cycle for 6 cycles
References
- CLG NH 3003: Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jones et al. 1979 | 1974-1977 | style="background-color:#1a9851"|Phase III (E-esc) | 1. CHOP-B | Not reported |
2. COP-Bleo | Might have superior CR rate |
Chemotherapy
Immunotherapy
References
- 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; SWOG. Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study. Cancer. 1979 Feb;43(2):417-25. link to original article contains verified protocol PubMed
- Update: Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Talley R, Butler JJ, Byrne GE Jr, Hartsock R, Dixon D, Salmon SE. Improved complete remission rates and survival for patients with large cell lymphoma treated with chemoimmunotherapy: a Southwest Oncology Group Study. Cancer. 1983 Mar 15;51(6):1083-90. PubMed
CHOP-B
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CHOP-B: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Bleomycin
B-CHOP: Bleomycin, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
BACOP: Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rodriguez et al. 1977 | 1973-1975 | Phase II | ||
Skarin et al. 1977 | 1973-1975 | Phase II | ||
Jones et al. 1979 | 1974-1977 | Phase III (E-esc) | 1. CHOP-BCG | Not reported |
2. COP-Bleo | Might have superior CR rate | |||
Newcomer et al. 1982 | NR in abstract | Randomized, <20 patients (E-de-esc) | ACOMLA | Seems to have superior RFS |
Bajetta et al. 1988 | 1976-1984 | Phase III (E-esc) | CVP | Seems to have superior FFFP |
Meyer et al. 1993 | 1982-1989 | Phase III (C) | esc-BACOP | Did not meet efficacy endpoints |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
- Bleomycin (Blenoxane) 4 mg/m2 IV once on day 1
21-day cycle for 8 cycles
References
- 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
- 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
- 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; SWOG. Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study. Cancer. 1979 Feb;43(2):417-25. link to original article contains verified protocol PubMed
- Update: Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Talley R, Butler JJ, Byrne GE Jr, Hartsock R, Dixon D, Salmon SE. Improved complete remission rates and survival for patients with large cell lymphoma treated with chemoimmunotherapy: a Southwest Oncology Group Study. Cancer. 1983 Mar 15;51(6):1083-90. PubMed
- 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
- 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
- Meyer RM, Quirt IC, Skillings JR, Cripps MC, Bramwell VH, Weinerman BH, Gospodarowicz MK, Burns BF, Sargeant AM, Shepherd LE, Zee B, Hryniuk WM. Escalated as compared with standard doses of doxorubicin in BACOP therapy for patients with non-Hodgkin's lymphoma. N Engl J Med. 1993 Dec 9;329(24):1770-6. link to original article PubMed
CHVP
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CHVP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vumon (Teniposide), Prednisone
CHVmP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vm26 (Teniposide), Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Burgers et al. 1983 (EORTC 20751) | 1975-1980 | Phase III (C) | CVP | Not reported |
Carde et al. 1991 | 1980-1986 | Phase III (C) | CHVmP-VB | Inferior OS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Teniposide (Vumon) 60 mg/m2 IV over 60 minutes once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
References
- EORTC 20751: Burgers JM, Somers R, Quasim MM, van Glabbekke M. Report on the EORTC 20751 lymphoma trial. Int J Radiat Oncol Biol Phys. 1983 Jan;9(1):11-5. link to original article PubMed
- Carde P, Meerwaldt JH, van Glabbeke M, Somers R, Monconduit M, Thomas J, de Wolf-Peeters C, de Pauw B, Tanguy A, Kluin-Nelemans JC, Noordijk EM, Regnier R, Bron D, Lustman-Marechal J, Caillou B, Bosq J, van Heerde P, van Unnik JAM, Burgers MV, Hayat M, Cosset JM, van der Schueren E, Wagener J, Hagenbeek A, Cattan A, Duez N, Tubiana M; EORTC Lymphoma Group. Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade non-Hodgkin's lymphoma (NHL): the 1980-1985 EORTC trial. Ann Oncol. 1991 Jun;2(6):431-5. link to original article contains protocol PubMed
CHVmP-VB
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CHVmP-VB: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vm26 (Teniposide), Prednisone, Vincristine, Bleomycin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Carde et al. 1991 | 1980-1986 | Phase III (E-esc) | CHVP | Superior OS |
Somers et al. 1994a | 1986-1991 | Phase III (C) | ProMACE-MOPP | Inferior ORR |
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Teniposide (Vumon) 60 mg/m2 IV over 60 minutes once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
- Vincristine (Oncovin) 2 mg IV once on day 15
- Bleomycin (Blenoxane) 10 mg IV once on day 15
References
- Carde P, Meerwaldt JH, van Glabbeke M, Somers R, Monconduit M, Thomas J, de Wolf-Peeters C, de Pauw B, Tanguy A, Kluin-Nelemans JC, Noordijk EM, Regnier R, Bron D, Lustman-Marechal J, Caillou B, Bosq J, van Heerde P, van Unnik JAM, Burgers MV, Hayat M, Cosset JM, van der Schueren E, Wagener J, Hagenbeek A, Cattan A, Duez N, Tubiana M; EORTC Lymphoma Group. Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade non-Hodgkin's lymphoma (NHL): the 1980-1985 EORTC trial. Ann Oncol. 1991 Jun;2(6):431-5. link to original article contains protocol PubMed
- Somers R, Carde P, Thomas J, Tirelli U, Keuning JJ, Bron D, Delmer A, de Bock R, De Wolf-Peeters C, van Glabbeke M, Duez N; EORTC. EORTC study of non-Hodgkin's lymphoma: phase III study comparing CHVmP-VB and ProMACE-MOPP in patients with stage II, III, and IV intermediate- and high-grade lymphoma. Ann Oncol. 1994;5 Suppl 2:85-9. Erratum in: Ann Oncol 1994 May;5(5):475. link to original article contains verified protocol PubMed
C-MOPP
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C-MOPP: CyclophosphaMide, Oncovin (Vincristine), Procarbazine, Prednisone
COPP: Cyclophosphamide, Oncovin (Vincristine), Procarbazine, Prednisone
Regimen
Study | Evidence | Comparator |
---|---|---|
Stein et al. 1974 | Phase III (E-esc) | VP |
DeVita et al. 1975 | Phase II |
Chemotherapy
References
- 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
- 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. link to original article PubMed
CNOP
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CNOP: Cyclophosphamide, Novantrone (Mitoxantrone), Oncovin (Vincristine), Prednisone
MCOP: Mitoxantrone, Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sonneveld et al. 1990 | NR | Phase II | ||
Pavlovsky et al. 1992a | 1985-1988 | Phase III (E-switch-ic) | CHOP | Seems not superior |
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
- Prednisone (Sterapred) 50 mg/m2 PO once per day on days 1 to 5
28-day cycle for 6 cycles
References
- Sonneveld P, Michiels JJ. Full dose chemotherapy in elderly patients with non-Hodgkin's lymphoma: a feasibility study using a mitoxantrone containing regimen. Br J Cancer. 1990 Jul;62(1):105-8. link to original article link to PMC article contains verified protocol PubMed
- Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, Milone G. Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. Ann Oncol. 1992 Mar;3(3):205-9. link to original article PubMed
- Update: Bezwoda W, Rastogi RB, Erazo Valla A, Diaz-Maqueo JC, Pavlovsky S, Morioka H, Resegotti L, Rueckle H, Somoza N, Moreno-Nogueira JA, Bernasconi C, Ho A, Burns I, Lardinois J, van der Merwe A, Richards E; Novantrone International Study Group. Long-term results of a multicentre randomised, comparative phase III trial of CHOP versus CNOP regimens in patients with intermediate- and high-grade non-Hodgkin's lymphomas. Eur J Cancer. 1995 Jun;31A(6):903-11. link to original article PubMed
CNOP (Prednisolone)
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CNOP: Cyclophosphamide, Novantrone (Mitoxantrone), Oncovin (Vincristine), Prednisolone
MCOP: Mitoxantrone, Cyclophosphamide, Oncovin (Vincristine), Prednisolone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bessell et al. 2003 (CLG NH 3003) | 1993-2000 | Phase III (E-switch-ic) | Modified CHOP | Seems not superior |
Chemotherapy
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg IV once on day 1
- Prednisolone (Millipred) 20 mg PO twice per day on days 1 to 5
21-day cycle for 6 cycles
References
- CLG NH 3003: Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. link to original article contains verified protocol PubMed
COMP
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COMP: Cyclophosphamide, Oncovin (Vincristine), Methotrexate, Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Anderson et al. 1983 | 1977-1979 | Phase III (E-de-esc) | LSA2-L2 | Did not meet primary endpoint of FFS |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV once per day on days 3, 10, 17, 24
- Methotrexate (MTX) 180 mg/m2 IV push, then 120 mg/m2 IV over 4 hours once on day 12
- Prednisone (Sterapred) 15 mg/m2 (maximum dose of 60 mg/day) PO four times per day on days 3 to 30, then taper off on days 31 to 37
CNS prophylaxis
- Methotrexate (MTX) 6.25 mg/m2 IT once per day on days 5, 31, 34
One course
Subsequent treatment
- COMP maintenance
References
- Anderson JR, Wilson JF, Jenkin DT, Meadows AT, Kersey J, Chilcote RR, Coccia P, Exelby P, Kushner J, Siegel S, Hammond D. Childhood non-Hodgkin's lymphoma: the results of a randomized therapeutic trial comparing a 4-drug regimen (COMP) with a 10-drug regimen (LSA2-L2). N Engl J Med. 1983 Mar 10;308(10):559-65. link to original article contains verified protocol PubMed
COP-Bleo
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COP-Bleo: Cyclophosphamide, Oncovin (Vincristine), Prednisone, Bleomycin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Coltman et al. 1977 | 1966-1974 | Non-randomized | ||
Jones et al. 1979 | 1974-1977 | Phase III (C) | 1. CHOP-BCG 2. CHOP-B |
Might have inferior CR rate |
Note: to our knowledge, this regimen was not tested as an experimental arm in a RCT prior to becoming a standard comparator arm.
Chemotherapy
References
- Coltman CA Jr, Luce JK, McKelvey EM, Jones SE, Moon TE; SWOG. Chemotherapy of non-Hodgkin's lymphoma: 10 years' experience in the Southwest Oncology Group. Cancer Treat Rep. 1977 Sep;61(6):1067-78. Pubmed
- 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; SWOG. Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study. Cancer. 1979 Feb;43(2):417-25. link to original article contains verified protocol PubMed
- Update: Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Talley R, Butler JJ, Byrne GE Jr, Hartsock R, Dixon D, Salmon SE. Improved complete remission rates and survival for patients with large cell lymphoma treated with chemoimmunotherapy: a Southwest Oncology Group Study. Cancer. 1983 Mar 15;51(6):1083-90. PubMed
CVP
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CVP: Cyclophosphamide, Vincristine, Prednisone
COP: Cyclophosphamide, Oncovin (Vincristine), Prednisone
VCP: Vincristine, Cyclophosphamide, Prednisone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hoogstraten et al. 1969 | NR | Phase III (E-esc) | Cyclophosphamide | Superior CR rate |
Bagley et al. 1972 | 1967-1970 | Phase II | ||
Benjamin et al. 1976 | 1970-1973 | Randomized, <20 pts (E-de-esc) | MOPP | Seems not superior |
Monfardini et al. 1977 | 1972-1974 | Phase III (C) | ABP | Seems not superior |
Bajetta et al. 1988 | 1976-1984 | Phase III (C) | BACOP | Seems to have inferior FFFP |
Chemotherapy
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycles
References
- Hoogstraten B, Owens AH, Lenhard RE, Glidewell OJ, Leone LA, Olson KB, Harley JB, Townsend SR, Miller S, Spurr CL. Combination chemotherapy in lymphosarcoma and reticulum cell sarcoma. Blood. 1969 Feb;33(2):370-8. link to original article PubMed
- 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
- Benjamin RS, Wiernik PH, O'Connell MJ, Chang P, Sutherland JC. A comparison of cyclophosphamide, vincristine, and prednisone (COP) with nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) in the treatment of nodular, poorly differentiated, lymphocytic lymphoma. Cancer. 1976 Nov;38(5):1896-902. link to original article PubMed
- 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. link to original article PubMed
- 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)
Regimen
Study | Evidence |
---|---|
Wilson et al. 2002 | Phase II |
Chemotherapy
- Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
- Prednisone (Sterapred) 60 mg/m2 PO twice per day on days 1 to 5
- Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2)
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 5
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/uL past nadir
- PCP prophylaxis with ONE of the following:
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day 3 days per week
- Atovaquone (Mepron) 1500 mg PO once per day
- Pentamidine (Nebupent) 300 mg nebulized every 28 days
21-day cycle for 6 to 8 cycles
Dose-adjustments
- Start cycle 1 as described above.
- Obtain CBCs twice per week for nadir measurements.
- If nadir ANC greater than 500/uL, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
- If nadir ANC less than 500/uL on 1 or 2 measurements, use same doses as last cycle.
- If nadir ANC less than 500/uL on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
- And/or if nadir platelet count less than 25 x 109/L 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 greater than 1000/uL and platelets greater than 100 x 109/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.
References
- 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
DICEP
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DICEP: Dose Intensive Cyclophosphamide, Etoposide, Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
Stewart et al. 2006 | Phase II |
Preceding treatment
- CHOP x 1
Chemotherapy
Subsequent treatment
- BEAM, then auto HSCT
References
- Stewart DA, Bahlis N, Valentine K, Balogh A, Savoie L, Morris DG, Jones A, Brown C, Russell JA. Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2006 Jun 15;107(12):4623-7. Epub 2006 Feb 7. link to original article contains protocol PubMed content property of HemOnc.org
F-MACHOP
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F-MACHOP: Fluorouracil, Methotrexate, Ara-C (Cytarabine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne
Regimen
Study | Evidence |
---|---|
Amadori et al. 1985 | Non-randomized |
Infanti et al. 1996 | Non-randomized |
Chemotherapy
- Fluorouracil (5-FU)
- Methotrexate (MTX)
- Cytarabine (Ara-C)
- Cyclophosphamide (Cytoxan)
- Doxorubicin (Adriamycin)
- Vincristine (Oncovin)
- Prednisone (Sterapred)
References
- 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
- 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. link to original article PubMed
- 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
- 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
- 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
APO: Adriamycin (Doxorubicin), Prednisone, Oncovin (Vincristine)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
McKelvey et al. 1976 | 1972-1974 | Phase III (E-de-esc) | CHOP | Seems not superior |
Laver et al. 2001 (POG 8615) | 1986-1991 | Phase III (C) | ACOP | Did not meet primary endpoint of EFS |
Laver et al. 2005 (POG 9315) | 1994-2000 | Non-randomized portion of RCT |
Chemotherapy
References
- 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. link to original article PubMed
- POG 8615: Laver JH, Mahmoud H, Pick TE, Hutchinson RE, Weinstein HJ, Schwenn M, Weitzman S, Murphy SB, Ochoa S, Shuster JJ; Pediatric Oncology Group. Results of a randomized phase III trial in children and adolescents with advanced stage diffuse large cell non Hodgkin's lymphoma: a Pediatric Oncology Group study. Leuk Lymphoma. 2001 Jul;42(3):399-405. link to original article PubMed
- POG 9315: Laver JH, Kraveka JM, Hutchison RE, Chang M, Kepner J, Schwenn M, Tarbell N, Desai S, Weitzman S, Weinstein HJ, Murphy SB. Advanced-stage large-cell lymphoma in children and adolescents: results of a randomized trial incorporating intermediate-dose methotrexate and high-dose cytarabine in the maintenance phase of the APO regimen: a Pediatric Oncology Group phase III trial. J Clin Oncol. 2005 Jan 20;23(3):541-7. link to original article 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 |
Chemotherapy
- Cyclophosphamide (Cytoxan)
- Doxorubicin (Adriamycin)
- Vincristine (Oncovin)
- Prednisone (Sterapred)
- Bleomycin (Blenoxane)
References
- 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Klimo et al. 1985a | 1981-1984 | Non-randomized | ||
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) | 1986-1991 | Phase III (E-esc) | 1. CHOP 2. m-BACOD 3. ProMACE-CytaBOM |
Did not meet endpoint of OS |
Sertoli et al. 1994 | 1987-1991 | Phase III (E-switch-ic) | ProMACE-MOPP | Seems not superior |
Gianni et al. 1997 | 1987-NR | Phase III (C) | High-dose sequential therapy | Inferior EFS |
Chemotherapy
- 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 twice per day
12-week course
References
- 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
- Update: Klimo P, Connors JM. Updated clinical experience with MACOP-B. Semin Hematol. 1987 Apr;24(2 Suppl 1):26-34. PubMed
- SWOG-8516: 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
- 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 link to PMC article PubMed
- Sertoli MR, Santini G, Chisesi T, Congiu AM, Rubagotti A, Contu A, Salvagno L, Coser P, Porcellini A, Vespignani M, Capnist G, Rossi E, Mangoni L, Fabris P, Vinante O, Tedeschi L, Endrizzi L, Miglio LP, Perrotta A, Rosso R, Damasio E, Rizzoli V. 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
- 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
- Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains verified protocol PubMed
- Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. link to original article contains protocol PubMed
m-BACOD
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m-BACOD: methotrexate (moderate dose), Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Dexamethasone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Skarin et al. 1983 | 1976-1981 | Non-randomized | ||
Shipp et al. 1990 | 1981-1986 | Non-randomized | ||
Gherlinzoni et al. 1990 | 1984-1986 | Phase III (C) | m-BNCOD | Did not meet endpoints of OS/RFS |
Gordon et al. 1992 | 1984-1988 | Phase III (E-esc) | CHOP | Did not meet endpoint of OS |
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) | 1986-1991 | Phase III (E-esc) | 1. CHOP 2. MACOP-B 3. ProMACE-CytaBOM |
Did not meet endpoint of OS |
Tilly et al. 2000 (LNH87-1) | 1987-1993 | Phase III (C) | ACVBP | Seems not superior |
Chemotherapy
- 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) IV once on day 1
- Dexamethasone (Decadron) 6 mg/m2 (no route specified) once per day on days 1 to 5
Supportive medications
- Folinic acid (Leucovorin) 10 mg/m2 IV or PO every 6 hours on days 9 & 10, 16 & 17, starting 24 hours after each Methotrexate (MTX)
21-day cycle for 10 cycles
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
References
- 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
- Gherlinzoni F, Guglielmi C, Mazza P, Amadori S, Mandelli F, Tura S. Phase III comparative trial (m-BACOD v m-BNCOD) in the treatment of stage II to IV non-Hodgkin's lymphomas with intermediate- or high-grade histology. Semin Oncol. 1990 Dec;17(6 Suppl 10):3-8; discussion 8-9. PubMed
- 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
- Gordon LI, Harrington D, Andersen J, Colgan J, Glick J, Neiman R, Mann R, Resnick GD, Barcos M, Gottlieb A, O'Connell M. Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma. N Engl J Med. 1992 Nov 5;327(19):1342-9. link to original article PubMed
- SWOG 8516: 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
- 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 link to PMC article PubMed
- LNH87-1: Tilly H, Mounier N, Lederlin P, Brière J, Dupriez B, Sebban C, Bosly A, Biron P, Nouvel C, Herbrecht R, Bordessoule D, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte. Randomized comparison of ACVBP and m-BACOD in the treatment of patients with low-risk aggressive lymphoma: the LNH87-1 study. 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gherlinzoni et al. 1990 | 1984-1986 | Phase III (E-switch-ic) | m-BACOD | Did not meet endpoints of OS/RFS |
Chemotherapy
- Methotrexate (MTX)
- Bleomycin (Blenoxane)
- Mitoxantrone (Novantrone)
- Cyclophosphamide (Cytoxan)
- Vincristine (Oncovin)
- Dexamethasone (Decadron)
References
- Gherlinzoni F, Guglielmi C, Mazza P, Amadori S, Mandelli F, Tura S. Phase III comparative trial (m-BACOD v m-BNCOD) in the treatment of stage II to IV non-Hodgkin's lymphomas with intermediate- or high-grade histology. Semin Oncol. 1990 Dec;17(6 Suppl 10):3-8; discussion 8-9. 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).
Chemotherapy
- 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
- 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
PACEBOM
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PACEBOM: Prednisolone, Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Bleomycin, Oncovin (Vincristine), Methotrexate
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Linch et al. 2000 | 1987-1991 | Phase III (E-esc) | CHOP | Might have superior cause-specific survival |
Chemotherapy
- Prednisolone (Millipred)
- Doxorubicin (Adriamycin)
- Cyclophosphamide (Cytoxan)
- Etoposide (Vepesid)
- Bleomycin (Blenoxane)
- Vincristine (Oncovin)
- Methotrexate (MTX)
References
- Linch DC, Smith P, Hancock BW, Hoskin PJ, Cunningham DC, Newland AC, Milligan D, Stevenson PA, Wood JK, Maclennan KA, Vaughan B, Vaughan G, Gregory WM; British National Lymphoma Investigation. A randomized British National Lymphoma Investigation trial of CHOP vs a weekly multi-agent regimen (PACEBOM) in patients with histologically aggressive non-Hodgkin's lymphoma. Ann Oncol. 2000;11 Suppl 1:87-90. link to original article PubMed
PEN
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PEN: Prednisone, Etoposide, Novantrone (Mitoxantrone)
Regimen
Study | Evidence |
---|---|
Goss et al. 1995 | Phase II |
Chemotherapy
References
- Goss P, Burkes R, Rudinskas L, King M, Chow W, Myers R, Davidson M, Poldre P, Crump M, Sutton D, Scott G. 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
PMitCEBO
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PMitCEBO: Prednisolone, Mitoxantrone, Cyclophosphamide, Etoposide, Bleomycin, Oncovin (Vincristine)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mainwaring et al. 2001 | 1993-1997 | Phase III (E-switch-ic) | PAdriaCEBO | Superior OS |
Burton et al. 2006 | 1997-1999 | Phase III (E-esc) | CHOP | Seems not superior |
Pfreundschuh et al. 2006 (NCIC-CTG LY.9) | 2000-2003 | Phase III (C) | 1. R-CHOP 2. R-CHOEP 3. R-MACOP-B 4. R-PMitCEBO |
Seems to have inferior EFS |
Chemotherapy
- Prednisolone (Millipred)
- Mitoxantrone (Novantrone)
- Cyclophosphamide (Cytoxan)
- Etoposide (Vepesid)
- Bleomycin (Blenoxane)
- Vincristine (Oncovin)
References
- Mainwaring PN, Cunningham D, Gregory W, Hoskin P, Hancock B, Norton AJ, MacLennan K, Smith P, Hudson GV, Linch D. Mitoxantrone is superior to doxorubicin in a multiagent weekly regimen for patients older than 60 with high-grade lymphoma: results of a BNLI randomized trial of PAdriaCEBO versus PMitCEBO. Blood. 2001 May 15;97(10):2991-7. link to original article PubMed
- Burton C, Linch D, Hoskin P, Milligan D, Dyer MJ, Hancock B, Mouncey P, Smith P, Qian W, MacLennan K, Jack A, Webb A, Cunningham D. A phase III trial comparing CHOP to PMitCEBO with or without G-CSF in patients aged 60 plus with aggressive non-Hodgkin's lymphoma. Br J Cancer. 2006 Mar 27;94(6):806-13. link to original article link to PMC article PubMed
- NCIC-CTG LY.9: Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains verified protocol PubMed NCT00064116
- Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. link to original article contains protocol PubMed
ProMACE-CytaBOM
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ProMACE-CytaBOM: Prolix (Prednisone), Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Cytarabine, Bleomycin, Oncovin (Vincristine), Methotrexate
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Longo et al. 1991 | 1981-1988 | Phase III (E-switch-ic) | ProMACE-MOPP | Seems to have superior OS |
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) | 1986-1991 | Phase III (E-esc) | 1. CHOP 2. MACOP-B 3. m-BACOD |
Did not meet endpoint of OS |
Chemotherapy
- 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 (Ara-C) 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 every 6 hours on day 9, starting 24 hours after Methotrexate (MTX)
- Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day throughout the course of treatment
Dose adjustments
- "If WBC count is at least 4 x 109/L, use 100% doses of all drugs
- If WBC count is 3 to 3.999 x 109/L, 100% prednisone, bleomycin, vincristine, cytarabine, and methotrexate; 75% cyclophosphamide, doxorubicin, and etoposide
- If WBC count is 2 to 2.999 x 109/L, 100% prednisone, bleomycin, vincristine, and methotrexate; 75% etoposide, cytarabine; 50% cyclophosphamide, doxorubicin
- If WBC count is 1 to 1.999 x 109/L, 100% prednisone, bleomycin, vincristine and methotrexate; 25% cyclophosphamide, doxorubicin, etoposide, and cytarabine
- If WBC count is 0 to 0.999 x 109/L, 100% prednisone, vincristine, and bleomycin; 50% methotrexate, no other drugs
- If platelet count is at least 100 x 109/L, use 100% doses of all drugs
- If platelet count is 50 to 99 x 109/L, 100% prednisone, bleomycin, vincristine, and methotrexate; 50% etoposide and cytarabine; 25% cyclophosphamide and doxorubicin
- If platelet count is 0 to 49 x 109/L, 100% prednisone, bleomycin, and vincristine; 50% methotrexate, no other drugs"
CNS prophylaxis
- Patients with initial bone or bone marrow involvement who achieved a CR were treated with 2400 cGy prophylactic cranial irradiation.
21-day cycle for 6 cycles or 2 cycles after maximum clinical response
References
- Longo DL, DeVita VT Jr, Duffey PL, Wesley MN, Ihde DC, Hubbard SM, Gilliom M, Jaffe ES, Cossman J, Fisher RI, Young RC. 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
- SWOG-8516: 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
- 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 link to PMC 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 | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fisher et al. 1983 | 1977-1981 | Non-randomized | ||
Longo et al. 1991 | 1981-1988 | Phase III (C) | ProMACE-CytaBOM | Seems to have inferior OS |
Somers et al. 1994a | 1986-1991 | Phase III (E-switch-ic) | CHVmP-VB | Superior ORR |
Sertoli et al. 1994 | 1987-1991 | Phase III (C) | MACOP-B | Seems not superior |
Chemotherapy
- Prednisone (Prolix)
- Methotrexate (MTX)
- Doxorubicin (Adriamycin)
- Cyclophosphamide (Cytoxan)
- Etoposide (Vepesid)
- Mechlorethamine (Mustargen)
- Vincristine (Oncovin)
- Procarbazine (Matulane)
- Prednisone (Sterapred)
References
- Fisher RI, DeVita VT Jr, Hubbard SM, Longo DL, Wesley R, Chabner BA, Young RC. Diffuse aggressive lymphomas: increased survival after alternating flexible sequences of proMACE and MOPP chemotherapy. Ann Intern Med. 1983 Mar;98(3):304-9. link to original article PubMed
- Longo DL, DeVita VT Jr, Duffey PL, Wesley MN, Ihde DC, Hubbard SM, Gilliom M, Jaffe ES, Cossman J, Fisher RI, Young RC. 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
- Somers R, Carde P, Thomas J, Tirelli U, Keuning JJ, Bron D, Delmer A, de Bock R, De Wolf-Peeters C, van Glabbeke M, Duez N. EORTC study of non-Hodgkin's lymphoma: phase III study comparing CHVmP-VB and ProMACE-MOPP in patients with stage II, III, and IV intermediate- and high-grade lymphoma. Ann Oncol. 1994;5 Suppl 2:85-9. Erratum in: Ann Oncol 1994 May;5(5):475. link to original article PubMed
- Sertoli MR, Santini G, Chisesi T, Congiu AM, Rubagotti A, Contu A, Salvagno L, Coser P, Porcellini A, Vespignani M, Capnist G, Rossi E, Mangoni L, Fabris P, Vinante O, Tedeschi L, Endrizzi L, Miglio LP, Perrotta A, Rosso R, Damasio E, Rizzoli V. 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 |
Chemotherapy
- Vincristine (Oncovin)
- Doxorubicin (Adriamycin)
- Bleomycin (Blenoxane)
- Etoposide (Vepesid)
- Prednisone (Sterapred)
References
- 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
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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 |
Chemotherapy
- Etoposide (Vepesid)
- Doxorubicin (Adriamycin)
- Cyclophosphamide (Cytoxan)
- Vincristine (Oncovin)
- Prednisone (Sterapred)
- Bleomycin (Blenoxane)
References
- Retrospective: Pichert G, Peters J, Stahel RA, Dommann C, Joss R, Gebbers JO, Kroner T, Sulser H, Honegger HP, Maurer R, Pampallona S. 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
- 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
VCAP
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VCAP: Vindesine, Cyclophosphamide, Adriamycin (Doxorubicin), Prednisone
Regimen
Study | Evidence |
---|---|
Bernard et al. 2005 | Phase II |
Chemotherapy
References
- Bernard M, Cartron G, Rachieru P, LeMevel A, Branger B, Le Maignan C, Berthou C, Ghandour C, Delwail V, Milpied N, Cassasus P, Celigny PS, Guyotat D, Lamy T, Desablens B; GOELAMS. Long-term outcome of localized high-grade non-Hodgkin's lymphoma treated with high dose CHOP regimen and involved field radiotherapy: results of a GOELAMS study. Haematologica. 2005 Jun;90(6):802-9. link to original article PubMed
VEPA
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VEPA: Vincristine, Endoxan (Cyclophosphamide), Prednisolone, Adriamycin (Doxorubicin)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shimoyama et al. 1988 (JCOG8101) | 1981-1983 | Phase III (C) | VEPA-M | Did not meet efficacy endpoints |
Note: while the drugs are the same as those used in CHOP, administration details vary significantly; see paper for details.
Chemotherapy
References
- JCOG8101: Shimoyama M, Ota K, Kikuchi M, Yunoki K, Konda S, Takatsuki K, Ichimaru M, Ogawa M, Kimura I, Tominaga S, Tsugane S, Taguchi H, Minato K, Takenaka T, Tobinai K, Kurita S, Oyama A, Hisano S, Kozuru M, Matsumoto M, Nomura K, Takiguchi T, Sugai S, Yamaguchi K, Hattori T, Kinoshita K, Tajima K, Suemasu K. Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M. J Clin Oncol. 1988 Jan;6(1):128-41. link to original article PubMed
VNCOP-B
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VNCOP-B: Vepesid (Etoposide), Novantrone (Mitoxantrone), Cyclophosphamide, Oncovin (Vincristine), Prednisone, Bleomycin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zinzani et al. 1997 | 1993-1995 | Phase III (C) | VNCOP-B & G-CSF | Did not meet endpoint of RFS |
Zinzani et al. 2002 | 1996-2001 | Phase III (C) | VNCOP-B & G-CSF x 12 wk | Seems not superior |
Chemotherapy
- Etoposide (Vepesid)
- Mitoxantrone (Novantrone)
- Cyclophosphamide (Cytoxan)
- Vincristine (Oncovin)
- Prednisone (Sterapred)
- Bleomycin (Blenoxane)
References
- Zinzani PL, Pavone E, Storti S, Moretti L, Fattori PP, Guardigni L, Falini B, Gobbi M, Gentilini P, Lauta VM, Bendandi M, Gherlinzoni F, Magagnoli M, Venturi S, Aitini E, Tabanelli M, Leone G, Liso V, Tura S. Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin's lymphoma. Blood. 1997 Jun 1;89(11):3974-9. link to original article PubMed
- Zinzani PL, Gherlinzoni F, Storti S, Zaccaria A, Pavone E, Moretti L, Gentilini P, Guardigni L, De Renzo A, Fattori PP, Falini B, Lauta VM, Mannina D, Zaja F, Mazza P, Volpe E, Lauria F, Aitini E, Ciccone F, Tani M, Stefoni V, Alinari L, Baccarani M, Tura S. Randomized trial of 8-week versus 12-week VNCOP-B plus G-CSF regimens as front-line treatment in elderly aggressive non-Hodgkin's lymphoma patients. Ann Oncol. 2002 Sep;13(9):1364-9. link to original article PubMed
VR-CHOP
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VR-CHOP: Velcade (Bortezomib), Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne
RB-CHOP: Rituximab, Bortezomib, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Predniso(lo)ne
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ruan et al. 2010 | 2004-2007 | Phase II | ||
Leonard et al. 2017 (C05013) | 2009-2013 | Randomized Phase II (E-esc) | R-CHOP | Seems not superior |
Targeted therapy
- Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1 & 4
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Chemotherapy
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications
- Ruan et al. 2010: "Standard" Acetaminophen (Tylenol) and Diphenhydramine (Benadryl) prior to Rituximab (Rituxan)
- C05013: Prophylaxis against VZV and PJP were recommended
21-day cycle for 6 cycles
References
- Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, Lacasce A, Morrison J, Elstrom R, Ely S, Chadburn A, Cesarman E, Coleman M, Leonard JP. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Feb 20;29(6):690-7. Epub 2010 Dec 28. link to original article contains verified protocol PubMed NCT00151320
- C05013: Leonard JP, Kolibaba KS, Reeves JA, Tulpule A, Flinn IW, Kolevska T, Robles R, Flowers CR, Collins R, DiBella NJ, Papish SW, Venugopal P, Horodner A, Tabatabai A, Hajdenberg J, Park J, Neuwirth R, Mulligan G, Suryanarayan K, Esseltine DL, de Vos S. Randomized phase II study of R-CHOP with or without bortezomib in previously untreated patients with non-germinal center B-cell-like diffuse large B-cell lymphoma. J Clin Oncol. 2017 Nov 1;35(31):3538-3546. Epub 2017 Sep 1. link to original article contains verified protocol PubMed
- REMoDL-B: Davies A, Cummin TE, Barrans S, Maishman T, Mamot C, Novak U, Caddy J, Stanton L, Kazmi-Stokes S, McMillan A, Fields P, Pocock C, Collins GP, Stephens R, Cucco F, Clipson A, Sha C, Tooze R, Care MA, Griffiths G, Du MQ, Westhead DR, Burton C, Johnson PWM. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019 May;20(5):649-662. Epub 2019 Apr 1. link to original article link to PMC article PubMed NCT01324596
Consolidation after upfront therapy
Cyclophosphamide & TBI
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Cy/TBI: Cyclophosphamide & Total Body Irradiation
Regimen
Study | Evidence |
---|---|
Takvorian et al. 1987 | Non-randomized |
Chemotherapy
- Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
Radiotherapy
- Total body irradiation (TBI) 1200 cGy in fractions on days –6 to –4 (pulmonary dosage was limited to 800 cGy)
References
- Takvorian T, Canellos GP, Ritz J, Freedman AS, Anderson KC, Mauch P, Tarbell N, Coral F, Daley H, Yeap B, Schlossman SF, Nadler LM. Prolonged disease-free survival after autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma with a poor prognosis. N Engl J Med. 1987 Jun 11;316(24):1499-505. link to original article PubMed
Relapsed or refractory, salvage therapy
DHAP
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DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Velasquez et al. 1988 | 1984-1986 | Phase II | ||
Philip et al. 1995 (PARMA) | 1987-1994 | Phase III (C) | DHAP x 2, then BEAC | Seems to have inferior OS |
Josting et al. 2005 | NR | Phase II |
Note: Velasquez et al. 1988 report giving 6 to 10 courses, usually 4 courses beyond maximum response. To our knowledge, this regimen was not tested as an experimental arm in a RCT prior to becoming a standard comparator arm.
Chemotherapy
- Dexamethasone (Decadron) 40 mg IV over 15 minutes once per day on days 1 to 4
- Cytarabine (Ara-C) as follows:
- Patients younger than 70: 2000 mg/m2 IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m2)
- Patients older than 70: 1000 mg/m2 IV over 3 hours every 12 hours on day 2 (total dose per cycle: 2000 mg/m2)
- Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours, started on day 1
Supportive medications
- Metoclopramide (Reglan) 1 mg/kg (route and frequency not indicated)
- Diphenhydramine (Benadryl) 25 mg IV (frequency not indicated)
3- to 4-week cycle for 2 cycles (PARMA & Josting et al. 2005) or up to 10 cycles (see note)
Subsequent treatment
- PARMA: Responders (PR/CR) after cycle 2: 4 more courses of DHAP versus BEAC, then autologous HSCT
- Josting et al. 2005: Responders (PR/CR) after cycle 2: HD-MTX with stem cell mobilization, then HDT, then autologous HSCT
References
- 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 verified protocol PubMed
- PARMA: Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. link to original article does not contain protocol PubMed
- Josting A, Sieniawski M, Glossmann JP, Staak O, Nogova L, Peters N, Mapara M, Dörken B, Ko Y, Metzner B, Kisro J, Diehl V, Engert A. High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma: results of a multicenter phase II study. Ann Oncol. 2005 Aug;16(8):1359-65. Epub 2005 Jun 6. link to original article contains protocol PubMed
EPIC regimen
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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 |
Chemotherapy
References
- 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 original article link to PMC article PubMed
- 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. link to original article PubMed
HAM
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HAM: High-dose Ara-C (Cytarabine) & Mitoxantrone
NOAC: NOvantrone (Mitoxantrone) & Ara-C (Cytarabine)
Regimen
Study | Evidence |
---|---|
Ho et al. 1989 | Phase II |
Chemotherapy
References
- 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. link to original article PubMed
MINE
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MINE: Mesna, Ifosfamide, Novantrone (Mitoxantrone), Etoposide
Regimen
Study | Evidence |
---|---|
Rodriguez et al. 1995 | Phase II |
Chemotherapy
- Ifosfamide (Ifex) 1333 mg/m2 IV over 60 minutes once per day on days 1 to 3
- Mitoxantrone (Novantrone) 8 mg/m2 IV once on day 1
- Etoposide (Vepesid) 65 mg/m2 IV over 60 minutes once per day on days 1 to 3
Supportive medications
- Mesna (Mesnex) 1333 mg/m2 IV over 60 minutes once per day on days 1 to 3
- Mesna (Mesnex) 500 mg PO once, diluted in water or juice, 4 hours following ifosfamide administration
21-day cycles
Subsequent treatment
- Patients who achieved a CR received a total of 6 cycles of MINE, then ESHAP consolidation x 3. If patients achieved a PR, then MINE was given to the point of maximal response, and then patients were crossed over to ESHAP.
References
- 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
VIM
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VIM: Vepesid (Etoposide), Ifosfamide, Mitoxantrone
Regimen
Study | Evidence |
---|---|
Hopfinger et al. 1995 | Phase II |
Chemotherapy
References
- 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. link to original article PubMed
VIPD
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VIPD: VP-16 (Etoposide), Ifosfamide, Platinol (Cisplatin), Dexamethasone
DVIP: Dexamethasone, VP-16 (Etoposide), Ifosfamide, Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
Haim et al. 1992 | Phase II |
Chemotherapy
References
- 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. link to original article PubMed
Consolidation after salvage therapy
ESHAP
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ESHAP: Etoposide, Solumedrol (Methylprednisolone), High dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
Rodriguez et al. 1995 | Phase II |
Preceding treatment
Chemotherapy
- Etoposide (Vepesid) 60 mg/m2 IV over 60 minutes 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 (Ara-C) 2000 mg/m2 IV over 2 hours once on day 5
- Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 100 mg/m2)
21-day cycle for 3 cycles
References
- 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
Relapsed or refractory, further lines of therapy
CEPP(B)
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CEPP(B): Cyclophosphamide, Etoposide, Procarbazine, Prednisone, (optional) Bleomycin
Regimen
Study | Evidence |
---|---|
Chao et al. 1990 | Phase II |
Chemotherapy
- Cyclophosphamide (Cytoxan)
- Etoposide (Vepesid)
- Procarbazine (Matulane)
- Prednisone (Sterapred)
- Bleomycin (Blenoxane)
References
- Chao NJ, Rosenberg SA, Horning SJ. CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin's lymphoma. Blood. 1990 Oct 1;76(7):1293-8. link to original article PubMed
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 |
Chemotherapy
References
- 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. link to original article PubMed
- 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. 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 |
Chemotherapy
References
- 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. link to original article PubMed
EPOCH
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EPOCH: Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
CHEOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Etoposide, Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence | Efficacy |
---|---|---|
Wilson et al. 1993 | Phase II | ORR: 87% |
Chemotherapy
- Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
- Prednisone (Sterapred) 60 mg/m2 PO on days 1 to 6
- Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2)
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 6
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
Supportive medications
- Filgrastim (Neupogen) 5 mcg/kg SC 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 twice per day 3 days per week
- Atovaquone (Mepron) 1500 mg PO once per day
- Pentamidine (Nebupent) 300 mg nebulized every 28 days
21-day cycle for 6 to 8 cycles
References
- Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD, Chabner BA. 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 verified protocol PubMed
- Update: Gutierrez M, Chabner BA, Pearson D, Steinberg SM, Jaffe ES, Cheson BD, Fojo A, Wilson WH. Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: an 8-year follow-up study of EPOCH. J Clin Oncol. 2000 Nov 1;18(21):3633-42. link to original article PubMed
ESHAP
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ESHAP: Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Velasquez et al. 1994 | 1986-1988 | Phase III (E-esc) | ESHA | Superior RR |
Avilés et al. 2010 | NR | Phase III (C) | R-ESHAP | Seems not superior |
Note: timing of cycle was variable and dependent on "recovery of the toxic effects"
Chemotherapy
- Etoposide (Vepesid) 40 mg/m2 IV over 60 minutes 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 (Ara-C) 2000 mg/m2 IV over 2 hours once on day 5
- Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 100 mg/m2)
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 (route not specified) "given regularly"
21- to 28-day cycle for 6 to 8 cycles
References
- 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
- Avilés A, Neri N, Huerta-Guzmán J, de Jesús Nambo M. ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2010 Apr;10(2):125-8. link to original article PubMed
Etoposide, Ifosfamide, Methotrexate
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IMVP-16: Ifosfamide, Methotrexate, VP-16 (Etoposide)
Regimen
Study | Evidence |
---|---|
Cabanillas et al. 1982 | Phase II |
Chemotherapy
References
- 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
GDP
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GDP: Gemcitabine, Dexamethasone, Platinol (Cisplatin)
Regimen
Study | Evidence |
---|---|
Crump et al. 2004 | Phase II |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
- Dexamethasone (Decadron) 40 mg IV or PO once per day on days 1 to 4
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1
21-day cycle for up to 6 cycles
References
- 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; National Cancer Institute of Canada Clinical Trials Group. 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
ICE
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ICE: Ifosfamide, Carboplatin, Etoposide
Regimen variant #1, inpatient
Study | Evidence |
---|---|
Moskowitz et al. 1999 | Phase II |
Zelenetz et al. 2003 | Phase II |
Third cycle intended to be followed by peripheral blood hematopoietic cell collection
Chemotherapy
- Ifosfamide (Ifex) 5,000 mg/m2 IV continuous infusion over 24 hours, started on day 2, mixed with Mesna (Mesnex)
- Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV bolus once on day 2
- Carboplatin AUC calculated based on a 12-hour creatinine clearance
- Etoposide (Vepesid) 100 mg/m2 IV bolus once per day on days 1 to 3
Supportive medications
- Mesna (Mesnex) 5,000 mg/m2 IV continuous infusion over 24 hours, started on day 2, mixed with Ifosfamide (Ifex)
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 5 to 12 (10 mcg/kg with cycle 3, given until collection of peripheral blood hematopoietic cells)
14-day cycle for 3 cycles; treatment can be delayed until ANC is greater than 1000/uL and platelet count greater than 50 x 109/L
Regimen variant #2, outpatient
Study | Evidence |
---|---|
Hertzberg et al. 2003 | Phase II, <20 pts in this subgroup |
Third cycle intended to be followed by peripheral blood hematopoietic cell collection
Chemotherapy
- Ifosfamide (Ifex) 1667 mg/m2 IV over 2 hours once per day on days 1 to 3, mixed with Mesna (Mesnex)
- Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV over 60 minutes once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV over 30 minutes once per day on days 1 to 3
Supportive medications
- Mesna (Mesnex) 1667 mg/m2 IV over 2 hours once per day on days 1 to 3, mixed with Ifosfamide (Ifex)
- Filgrastim (Neupogen) 5 mcg/kg SC once per day, started on day 5
21-day cycle for 3 cycles
References
- Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lyons N, Agus DB, Goy A, Jurcic J, Noy A, O'Brien J, Portlock CS, Straus DS, Childs B, Frank R, Yahalom J, Filippa D, Louie D, Nimer SD, Zelenetz AD. Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3776-85. link to original article contains verified protocol PubMed
- Zelenetz AD, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz CH. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003;14 Suppl 1:i5-10. link to original article contains verified protocol PubMed
- Hertzberg MS, Crombie C, Benson W, Taper J, Gottlieb D, Bradstock KF. Outpatient-based ifosfamide, carboplatin and etoposide (ICE) chemotherapy in transplant-eligible patients with non-Hodgkin's lymphoma and Hodgkin's disease. Ann Oncol. 2003;14 Suppl 1:i11-6. link to original article contains verified protocol PubMed
R-INO
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R-INO: Rituximab, INOtuzumab ozogamicin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fayad et al. 2013 (B1931004) | 2006-NR | Phase I/II | ||
Dang et al. 2017 (B1931008) | 2011-2013 | Phase III (E-switch-ooc) | Investigator's choice of: 1. BR 2. Gemcitabine & Rituximab |
Did not meet primary endpoint of OS |
Targeted therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Antibody-drug conjugate therapy
- Inotuzumab ozogamicin (Besponsa) 1.8 mg/m2 IV once on day 2
28-day cycle for up to 8 cycles
References
- B1931004: Fayad L, Offner F, Smith MR, Verhoef G, Johnson P, Kaufman JL, Rohatiner A, Advani A, Foran J, Hess G, Coiffier B, Czuczman M, Giné E, Durrant S, Kneissl M, Luu KT, Hua SY, Boni J, Vandendries E, Dang NH. Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. J Clin Oncol. 2013 Feb 10;31(5):573-83. Epub 2013 Jan 7. link to original article link to PMC article contains verified protocol PubMed NCT00299494
- B1931008: Dang NH, Ogura M, Castaigne S, Fayad LE, Jerkeman M, Radford J, Pezzutto A, Bondarenko I, Stewart DA, Shnaidman M, Sullivan S, Vandendries E, Tobinai K, Ramchandren R, Hamlin PA, Giné E, Ando K. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2018 Aug;182(4):583-586. Epub 2017 Jul 5. link to original article link to PMC article contains protocol PubMed NCT01232556