Diffuse large B-cell lymphoma - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main DLBCL page for current regimens.

50 regimens on this page
58 variants on this page

Contents


Untreated

ABP

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ABP: Adriamycin (Doxorubicin), Bleomycin, Prednisone

Regimen

Study Evidence Comparator Efficacy
Monfardini et al. 1977 Phase III CVP Seems not superior

Chemotherapy

References

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

ACE

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ACE: Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide

Regimen

Study Evidence Comparator Efficacy
Dumontet et al. 2000 Phase II
Haioun et al. 2009 Phase III ACVBP Seems not superior

Chemotherapy

References

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

ACOMLA

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

Regimen

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

Chemotherapy

References

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

ACVBP

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

Regimen

Study Evidence Comparator Efficacy
Tilly et al. 2000 (LNH87-1) Phase III m-BACOD Seems not superior
Tilly et al. 2003 Phase III CHOP Seems to have superior OS
Reyes et al. 2005 (LNH 93-01) Phase III CHOP, then RT Superior OS
Haioun et al. 2009 Phase III ACE Seems not superior
Ketterer et al. 2013 (LNH03-1B) Phase III ACVBP-R Seems to have inferior PFS

Induction Regimen

CNS prophylaxis

Supportive medications

21-day cycle for 4 cycles, followed by:

Consolidation Regimen, part 1

Supportive medications

14-day cycle for 2 cycles, followed by:

Consolidation Regimen, part 2

Supportive medications

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

Consolidation Regimen, part 3

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

References

  1. 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'Etudes 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
  2. Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. Epub 2003 Aug 14. link to original article contains verified protocol PubMed
  3. 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 (GELA). ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005 Mar 24;352(12):1197-205. link to original article PubMed
  4. Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. link to original article PubMed
  5. 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. 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

BCOP

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BCOP: BCNU (Carmustine), Cyclophosphamide, Oncovin (Vincristine), Prednisone

Regimen

Study Evidence Comparator Efficacy
Gams et al. 1985 Phase III CHOP Might have inferior OS

Chemotherapy

References

  1. Gams RA, Rainey M, Dandy M, Bartolucci AA, Silberman H, Omura G. 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

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

References

  1. Laurence J, Coleman M, Allen SL, Silver RT, Pasmantier M. Combination chemotherapy of advanced diffuse histiocytic lymphoma with the six-drug COP-BLAM regimen. Ann Intern Med. 1982 Aug;97(2):190-5. link to original article PubMed
  2. Armitage JO, Weisenburger DD, Hutchins M, Moravec DF, Dowling M, Sorensen S, Mailliard J, Okerbloom J, Johnson PS, Howe D, 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
  3. 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
  4. 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

21-day cycle for 6 to 8 cycles

References

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

CHOEP-14

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CHOEP-14: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 14 days
CHOPE: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Etoposide
VACOP: Vepesid (Etoposide), Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone

Regimen

Study Evidence Comparator Efficacy Toxicity
Pfreundschuh et al. 2004 (NHL-B1) Phase III (E) CHOP-21
CHOP-14
Superior EFS Seems more toxic
CHOEP-21
CHOP-21
Seems to have superior OS
Pfreundschuh et al. 2004 (NHL-B2) Phase III (E) CHOEP-21
CHOP-21
CHOP-14
Seems not superior Seems more toxic

Chemotherapy

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 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

  1. 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
  2. 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
  3. 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
    1. 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 (MInT) 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

CHOEP-21

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CHOEP-21: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone every 21 days
CHOPE: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Etoposide
VACOP: Vepesid (Etoposide), Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Prednisone

Regimen

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

Chemotherapy

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

  1. 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
  2. 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
  3. 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
  4. 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
    1. 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 (MInT) 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

Variant #1, 3 cycles

Study Evidence Comparator Efficacy
Miller et al. 1998 (SWOG S8736) Phase III See link See link
Reyes et al. 2005 (LNH 93-01) Phase III (C) ACVBP Inferior OS
Persky et al. 2014 (SWOG S0313) 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

21-day cycle for 3 cycles

Subsequent treatment

Variant #2, 6 cycles

Study Evidence Comparator Efficacy
Pfreundschuh et al. 2004 (NHL-B1) Phase III (C) CHOEP-14
CHOP-14
Seems to have inferior OS
CHOEP-21 Inferior EFS
Pfreundschuh et al. 2004 (NHL-B2) Phase III (C) CHOEP-14 Seems not superior
CHOEP-21 Seems not superior
CHOP-14 Inferior OS
Verdonck et al. 2007 Phase III (C) I-CHOP Seems not superior

Preceding treatment

Chemotherapy

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

Variant #3, 6 to 8 cycles

Study Evidence Comparator Efficacy
Habermann et al. 2006 (ECOG 4494/CALGB 9793) Phase III (C) R-CHOP Seems to have inferior FFS

Chemotherapy

Supportive medications

21-day cycle for 6 to 8 cycles

Subsequent treatment

Variant #4, 8 cycles, flat dose prednisone

Study Evidence Comparator Efficacy
Elias et al. 1978 Non-randomized
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) Phase III MACOP-B Seems not superior
m-BACOD Seems not superior
ProMACE-CytaBOM Seems not superior
Miller et al. 1998 (SWOG S8736) Phase III (C) CHOP x 3, then RT Seems to have inferior OS

Chemotherapy

21-day cycle for 8 cycles

Variant #5, 8 cycles, 40 mg/m2 prednisone

Study Evidence Comparator Efficacy
Coiffier et al. 2002 (LNH-98.5) Phase III R-CHOP Inferior OS
Tilly et al. 2003 Phase III ACVBP Seems to have inferior OS

Chemotherapy

Supportive medications

  • Filgrastim (Neupogen) used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia

21-day cycle for 8 cycles

Variant #6, 8 cycles, uncapped vincristine

Study Evidence Comparator Efficacy
Gams et al. 1985 Phase III BCOP Might have superior OS

Chemotherapy

21-day cycle for 8 cycles

References

  1. McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93. PubMed
  2. 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
  3. Gams RA, Rainey M, Dandy M, Bartolucci AA, Silberman H, Omura G. 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
  4. Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, et al. 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
  5. SWOG-8516/Intergroup 0067: Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. link to original article PubMed
    1. Update: Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study. Ann Oncol. 1994;5 Suppl 2:91-5. PubMed
    2. Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article PubMed
  6. Tondini C, Zanini M, Lombardi F, Bengala C, Rocca A, Giardini R, Buzzoni R, Valagussa P, Bonadonna G. Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas. J Clin Oncol. 1993 Apr;11(4):720-5. link to original article PubMed
  7. SWOG S8736: Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2;339(1):21-6. link to original article contains verified protocol PubMed
    1. Update: Stephens DM, Li H, LeBlanc ML, Puvvada SD, Persky D, Friedberg JW, Smith SM. Continued Risk of Relapse Independent of Treatment Modality in Limited-Stage Diffuse Large B-Cell Lymphoma: Final and Long-Term Analysis of Southwest Oncology Group Study S8736. J Clin Oncol. 2016 Sep 1;34(25):2997-3004. Epub 2016 Jul 5. link to original article PubMed
  8. 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. 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
    1. 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
    2. 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
    3. 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 (GELA). 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
  9. 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
  10. 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
  11. 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
  12. Horning SJ, Weller E, Kim K, Earle JD, O'Connell MJ, Habermann TM, Glick JH. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol. 2004 Aug 1;22(15):3032-8. Epub 2004 Jun 21. link to original article PubMed
  13. 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 (GELA). ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005 Mar 24;352(12):1197-205. link to original article PubMed
  14. 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
    1. 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 (MInT) 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
  15. ECOG 4494/CALGB 9793: 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
  16. Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thiéblemont C, Fermé C, Quesnel B, Martin C, Gisselbrecht C, Tilly H, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2007 Mar 1;25(7):787-92. Epub 2007 Jan 16. link to original article contains protocol PubMed
  17. 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
  18. 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

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
CHOP-DI
I-CHOP

Variant #1

Study Evidence
Blayney et al. 2003 (CHOP-DI, SWOG 9349) Phase II

Chemotherapy

Supportive medications

14-day cycle for up to 6 cycles

Variant #2

Study Evidence Comparator Efficacy
Verdonck et al. 2007 Phase III CHOP Seems not superior

Chemotherapy

Supportive medications

14-day cycle for 6 cycles

Variant #3

Study Evidence Comparator Efficacy
Pfreundschuh et al. 2004 (NHL-B1) Phase III CHOEP-14 Inferior EFS
CHOEP-21
CHOP
Seems to have superior OS
Pfreundschuh et al. 2008 (RICOVER-60) Phase III CHOP-14 x 8 Seems to have inferior EFS
R-CHOP-14 x 6 Inferior OS
R-CHOP-14 x 8 Inferior PFS

Preceding treatment

Chemotherapy

Supportive medications

  • (per Pfreundschuh et al. 2004):
  • 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

14-day cycle for 6 cycles

Radiation therapy for initial bulky disease

"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter >=7.5 cm) or extranodal involvement"

Variant #4

Study Evidence Comparator Efficacy
Pfreundschuh et al. 2008 (RICOVER-60) Phase III CHOP-14 x 6 Seems to have superior EFS
R-CHOP-14 x 6 Not reported
R-CHOP-14 x 8 Not reported

Preceding treatment

Chemotherapy

Supportive medications

  • 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

14-day cycle for 8 cycles

Radiation therapy for initial bulky disease

"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter >=7.5 cm) or extranodal involvement"

References

  1. Blayney DW, LeBlanc ML, Grogan T, Gaynor ER, Chapman RA, Spiridonidis CH, Taylor SA, Bearman SI, Miller TP, Fisher RI; Southwest Oncology Group. 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
  2. Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains verified protocol PubMed
  3. Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. link to original article PubMed
  4. 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
  5. 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 (DSHNHL). 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

CHOP Modified

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mCHOP: modified Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study Evidence Comparator Efficacy
Bessell et al. 2003 (CLG NH 3003) Phase III MCOP Seems not superior

This regimen is designed for elderly patients and is of lower intensity than standard CHOP.

Chemotherapy

21-day cycle for 6 cycles

References

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

Chemotherapy

References

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

CHOP-B

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

Regimen

Study Evidence Comparator Efficacy
Rodriguez et al. 1977 Phase II
Skarin et al. 1977 Phase II
Jones et al. 1979 Phase III CHOP-BCG Seems not superior
COP-Bleo Seems not superior
Newcomer et al. 1982 Randomized, <20 patients ACOMLA Seems to have superior RFS
Coiffier et al. 1986 (LNH-80) Phase II
Bajetta et al. 1988 Phase III CVP Seems to have superior FFFP

Chemotherapy

References

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

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 VP
DeVita et al. 1975 Phase II

Chemotherapy

References

  1. Stein RS, Moran EM, Desser RK, Miller JB, Golomb HM, Ultmann JE. Combination chemotherapy of lymphomas other than Hodgkin's disease. Ann Intern Med. 1974 Nov;81(5):601-8. link to original article PubMed
  2. 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 Evidence Comparator Efficacy
Sonneveld et al. 1990 Phase II
Pavlovsky et al. 1992 Phase III CHOP Seems not superior
Bessell et al. 2003 Phase III Modified CHOP Seems not superior

Chemotherapy

21-day cycle for 6 cycles

References

  1. 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 PubMed
  2. Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, et al. 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
  3. 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

COP-Bleo

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

Regimen

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

Chemotherapy

References

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

CVP

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CVP: Cyclophosphamide, Vincristine, Prednisone
COP
COP protocol 2
VCP

Regimen

Study Evidence Comparator Efficacy
Bagley et al. 1972 Phase II
Benjamin et al. 1976 RCT, <20 pts MOPP Seems not superior
Monfardini et al. 1977 Phase III ABP Seems not superior
Bajetta et al. 1988 Phase III BACOP Seems to have inferior FFFP

Chemotherapy

21-day cycles

References

  1. Bagley CM Jr, Devita VT Jr, Berard CW, Canellos GP. Advanced lymphosarcoma: intensive cyclical combination chemotherapy with cyclophosphamide, vincristine, and prednisone. Ann Intern Med. 1972 Feb;76(2):227-34. link to original article PubMed
  2. 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
  3. Monfardini S, Tancini G, DeLena M, Villa E, Valagussa P, Bonadonna G. Cyclophosphamide, vincristine, and prednisone (CVP) versus adriamycin, bleomycin, and prednisone (ABP) in stage IV non-Hodgkin's lymphomas. Med Pediatr Oncol. 1977;3(1):67-74. PubMed
  4. 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

Supportive medications

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

  1. Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. link to original article contains verified protocol PubMed

F-MACHOP

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

Regimen

Study Evidence
Amadori et al. 1985 Non-randomized

Chemotherapy

References

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

HOP

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

Regimen

Study Evidence Comparator
McKelvey et al. 1976 Phase III CHOP

Chemotherapy

References

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

LD-ACOP-B

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

Regimen

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

Chemotherapy

References

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

MACOP-B

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

Regimen

Study Evidence Comparator Efficacy
Klimo et al. 1985 Non-randomized
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) Phase III CHOP

m-BACOD
ProMACE-CytaBOM

Seems not superior
Sertoli et al. 1994 Phase III ProMACE-MOPP Seems not superior
Gianni et al. 1997 Phase III High-dose sequential therapy Inferior EFS

Chemotherapy

CNS prophylaxis

Supportive medications

One 12-week course

References

  1. Klimo P, Connors JM. MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med. 1985 May;102(5):596-602. link to original article PubMed
    1. Update: Klimo P, Connors JM. Updated clinical experience with MACOP-B. Semin Hematol. 1987 Apr;24(2 Suppl 1):26-34. PubMed
  2. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. link to original article PubMed
    1. Update: Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study. Ann Oncol. 1994;5 Suppl 2:91-5. PubMed
    2. Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article PubMed
  3. Sertoli MR, Santini G, Chisesi T, Congiu AM, Rubagotti A, Contu A, Salvagno L, Coser P, Porcellini A, Vespignani M, 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
  4. Gianni AM, Bregni M, Siena S, Brambilla C, Di Nicola M, Lombardi F, Gandola L, Tarella C, Pileri A, Ravagnani F, Valagussa P, Bonadonna G. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med. 1997 May 1;336(18):1290-7. link to original article PubMed
  5. 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
    1. 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 (MInT) 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 Evidence Comparator
Skarin et al. 1983 Non-randomized
Guglielmi et al. 1989 Phase III m-BNCOD
Shipp et al. 1990 Non-randomized
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) Phase III CHOP; MACOP-B; ProMACE-CytaBOM
Tilly et al. 2000 (LNH87-1) Phase III ACVBP

Chemotherapy

Dose adjustments:

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

Supportive medications

21-day cycle for 10 cycles

References

  1. Skarin AT, Canellos GP, Rosenthal DS, Case DC Jr, MacIntyre JM, Pinkus GS, Moloney WC, Frei E 3rd. Improved prognosis of diffuse histiocytic and undifferentiated lymphoma by use of high dose methotrexate alternating with standard agents (M-BACOD). J Clin Oncol. 1983 Feb;1(2):91-8. link to original article PubMed
  2. Guglielmi C, Gherlinzoni F, Amadori S, Mazza P, Mantovani L, Lauria F, Martelli M, Zinzani PL, Greco V, Poletti G, et al. A phase III comparative trial of m-BACOD vs m-BNCOD in the treatment of stage II-IV diffuse non-Hodgkin's lymphomas. Haematologica. 1989 Nov-Dec;74(6):563-9. PubMed
  3. Shipp MA, Yeap BY, Harrington DP, Klatt MM, Pinkus GS, Jochelson MS, Rosenthal DS, Skarin AT, Canellos GP. The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen. J Clin Oncol. 1990 Jan;8(1):84-93. link to original article contains verified protocol PubMed
  4. 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
    1. Update: Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study. Ann Oncol. 1994;5 Suppl 2:91-5. PubMed
    2. Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article PubMed
  5. 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'Etudes 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 Evidence Comparator
Guglielmi et al. 1989 Phase III m-BACOD

Chemotherapy

References

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

P/DOCE

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

Regimen

Study Evidence
O'Reilly et al. 1993 Phase II

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

Chemotherapy

8-week course

References

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

PEN

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PEN: Prednisone, Etoposide, Novantrone (Mitoxantrone)

Regimen

Study Evidence
Goss et al. 1995 Phase II

Chemotherapy

References

  1. 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 Evidence Comparator Efficacy
Pfreundschuh et al. 2006 (MInT) Phase III R-CHOP
R-CHOEP
R-MACOP-B
R-PMitCEBO
Seems to have inferior EFS

Chemotherapy

References

  1. 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 PubMed
  2. 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
    1. 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 (MInT) 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 Evidence Comparator Efficacy
Longo et al. 1991 Phase III ProMACE-MOPP Seems to have superior OS
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) Phase III CHOP; MACOP-B; m-BACOD Seems not superior

Chemotherapy

Supportive medications

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 .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

  1. 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
  2. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. link to original article PubMed
    1. Update: Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study. Ann Oncol. 1994;5 Suppl 2:91-5. PubMed
    2. Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article PubMed

ProMACE-MOPP

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

Regimen

Study Evidence Comparator Efficacy
Longo et al. 1991 Phase III ProMACE-CytaBOM Seems to have inferior OS
Sertoli et al. 1994 Phase III MACOP-B Seems not superior

Chemotherapy

References

  1. 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
  2. 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

References

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

VACOP-B

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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

References

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

VCAP

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VCAP: Vindesine, Cyclophosphamide, Adriamycin (Doxorubicin), Prednisone

Regimen

Study Evidence
Bernard et al. 2005 Phase II

Chemotherapy

References

  1. 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; French GOELAMS Group. 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

VR-CHOP

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VR-CHOP: Velcade (Bortezomib), Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study Evidence Comparator Efficacy
Ruan et al. 2010 Phase II
Leonard et al. 2017 Randomized Phase II R-CHOP Seems not superior

Chemotherapy

Supportive medications

21-day cycle for 6 cycles

References

  1. 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
  2. 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

Relapsed or refractory, salvage therapy

DHAP

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DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence Comparator Efficacy
Velasquez et al. 1988 Phase II
Philip et al. 1995 (PARMA) Phase III DHAP x 2, then BEAC Seems to have inferior OS

Chemotherapy

  • Dexamethasone (Decadron) 40 mg IV over 15 minutes once per day on days 1 to 4
  • Cytarabine (Cytosar) as follows:
    • Patients younger than 70: 2000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
    • Patients older than 70: 1000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
  • Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1

Supportive medications

3 to 4 week cycle "according to the extent of myelosuppression"

Velasquez et al. 1988 report 6 to 10 courses, usually 4 courses beyond maximum response. The PARMA trial collected bone marrow after cycle 1 and then randomized responders (PR/CR) after cycle 2 to 4 more courses of DHAP versus BEAC, then autologous HSCT.

References

  1. Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, Barlogie B. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. link to original article contains verified protocol PubMed
  2. 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

DVIP

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

Regimen

Study Evidence
Haim et al. 1992 Phase II

Chemotherapy

References

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

EPIC 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

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

MINE

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MINE: Mesna, Ifosfamide, Novantrone (Mitoxantrone), Etoposide

Regimen

Study Evidence
Rodriguez et al. 1995 Phase II

Chemotherapy

Supportive medications

  • Mesna (Mesnex) 1.33 g/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

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

References

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

NOAC

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

Regimen

Study Evidence
Ho et al. 1989 Phase II

Chemotherapy

References

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

VIM

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VIM: Vepesid (Etoposide), Ifosfamide, Mitoxantrone

Regimen

Study Evidence
Hopfinger et al. 1995 Phase II

Chemotherapy

References

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

Consolidation after salvage therapy

ESHAP

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ESHAP: Etoposide, High dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence
Rodriguez et al. 1995 Phase II

Preceding treatment

Chemotherapy

21-day cycle for 3 cycles

References

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

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

References

  1. 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

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

DICEP

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

Regimen

Study Evidence
Neidhart et al. 1994 Phase II

Chemotherapy

References

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

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

Supportive medications

21-day cycle for 6 to 8 cycles

References

  1. 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

ESHA

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

Regimen

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

Chemotherapy

Supportive medications

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

References

  1. Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. link to original article contains verified protocol PubMed

ESHAP

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ESHAP: Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence Comparator Efficacy
Velasquez et al. 1994 Phase III ESHA Superior RR
Avilés et al. 2010 Phase III R-ESHAP Seems not superior

Chemotherapy

Supportive medications

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

References

  1. Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. link to original article contains verified protocol PubMed
  2. 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

GDP

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GDP: Gemcitabine, Dexamethasone, Platinol (Cisplatin)

Regimen

Study Evidence
Crump et al. 2004 Phase II

Chemotherapy

21-day cycle for up to 6 cycles

References

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

ICE

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ICE: Ifosfamide, Carboplatin, Etoposide

Regimen

Study Evidence
Zelenetz et al. 2003 Phase II

Third cycle intended to be followed by peripheral blood hematopoietic cell collection

Chemotherapy

14-day cycle for 3 cycles

Supportive medications

  • Mesna (Mesnex) 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together 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)

References

  1. 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 PubMed
  2. 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
  3. 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 PubMed

IMVP-16

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

Regimen

Study Evidence
Cabanillas et al. 1982 Phase II

Chemotherapy

References

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