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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only.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

64 regimens on this page
79 variants on this page


Untreated

ABP

ABP: Adriamycin (Doxorubicin), Bleomycin, Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Monfardini et al. 1977 1972-1974 Phase 3 (E-switch-ic) CVP Did not meet endpoint of ORR

Chemotherapy

Glucocorticoid therapy

21-day cycle for at least 6 cycles

References

  1. Monfardini S, Tancini G, De Lena 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 contains dosing details in manuscript PubMed

ACE

ACE: Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Dumontet et al. 2000 1995-1998 Phase 2
Haioun et al. 2009 (LNH 98-3) 1999-2004 Phase 3 (E-de-esc) ACVBP Did not meet endpoint of OS

Chemotherapy

Glucocorticoid therapy

CNS therapy, prophylaxis

Supportive therapy

  • G-CSF 5 mcg/kg/day SC on days 6 to 13

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. link to original article PubMed
  2. 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 dosing details in manuscript PubMed NCT00169169

ACOMLA

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Newcomer et al. 1982 NR in abstract Randomized, fewer than 20 patients CHOP-B Seems to have inferior RFS

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

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

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Tilly et al. 2000 (LNH87-1) 1987-1993 Phase 3 (E-esc) m-BACOD Did not meet primary endpoint of FFS
Tilly et al. 2003 1993-1998 Phase 3 (E-esc) CHOP Seems to have superior OS
Morel et al. 2010 (LNH93-2) 1993-1998 Phase 3 (C) ECVBP Did not meet primary endpoint of EFS
Reyes et al. 2005 (LNH 93-01) 1993-2000 Phase 3 (E-esc) CHOP, then RT Superior OS (secondary endpoint)
OS60: 90% vs 81%
Haioun et al. 2009 (LNH 98-3) 1999-2004 Phase 3 (C) ACE Did not meet endpoint of OS
Ketterer et al. 2013 (LNH03-1B) 2003-2008 Phase 3 (C) R-ACVBP Seems to have inferior PFS

Induction

Chemotherapy

Glucocorticoid therapy

CNS therapy, prophylaxis

Supportive therapy

21-day cycle for 4 cycles, followed by:


Consolidation, part 1

Chemotherapy

Supportive therapy

14-day cycle for 2 cycles, followed in 2 weeks by:


Consolidation, part 2 (EI)

Chemotherapy

Supportive therapy

14-day cycle for 4 cycles, followed in 2 weeks by:


Consolidation, part 3

Chemotherapy

14-day cycle for 2 cycles

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'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
  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 dosing details in manuscript 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. 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. 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 NCT00169169
  5. 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
  6. 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 NCT00140595

ACVBP (Methylprednisolone)

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

Regimen

Study Dates of enrollment Evidence
Coiffier et al. 1986 (LNH-80) 1980-1984 Phase 2

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

Glucocorticoid therapy

CNS therapy, prophylaxis

15-day cycle for 3 cycles; cycles were delayed until ANC greater than 1500/μL

Subsequent treatment

References

  1. 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 dosing details in manuscript PubMed

BCOP

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gams et al. 1985 1977-1981 Phase 3 (E-switch-ic) CHOP Might have inferior OS

Chemotherapy

Glucocorticoid therapy

28-day cycle for 6 cycles

References

  1. 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 dosing details in manuscript PubMed

CAP-BOP

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

Regimen

Study Dates of enrollment Evidence
Laurence et al. 1982 1977-1981 Phase 2
Boyd et al. 1988 1981-1984 Phase 2
Armitage et al. 1986 1982-1984 Phase 2
Vose et al. 1988 1982-1986 Phase 2

Chemotherapy

Glucocorticoid therapy

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

CCOP: Cyclophosphamide, Caelyx (Pegylated liposomal doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study Dates of enrollment Evidence
Martino et al. 2002 1998-2000 Phase 2

Chemotherapy

Glucocorticoid therapy

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 dosing details in manuscript PubMed

CEEP

CEEP: Cyclophosphamide, Epirubicin, Eldesine (Vindesine), Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Milpied et al. 2004 (GOELAMS 072) 1994-1999 Phase 3 (E-esc) CHOP Seems to have superior EFS

Chemotherapy

Glucocorticoid therapy

CNS therapy, prophylaxis

2 cycles

Subsequent treatment

References

  1. 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 dosing details in manuscript PubMed

CEOP

CEOP: Cyclophosphamide, Epirubicin, Oncovin (Vincristine), Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Economopoulos et al. 2002 1993-1999 Phase 3 (C) CNOP Did not meet efficacy endpoints
Chamorey et al. 2005 1994-1998 Phase 3 (C) MEMID Did not meet primary endpoint of OS
Economopoulos et al. 2007 (HE22A99) 1999-2005 Phase 3 (C) CEOP-14 Did not meet primary endpoint of OS

Chemotherapy

Glucocorticoid therapy

21-day cycles

References

  1. 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 dosing details in manuscript PubMed
  2. 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
  3. 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)

CEOP: Cyclophosphamide, Epirubicin, Oncovin (Vincristine), Prednisolone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Hertzberg et al. 2014 (ALLG NHL07) 1994-1999 Phase 3 (C) DI-CEOP Did not meet primary endpoint of OS60

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 cycles

References

  1. 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 dosing details in abstract PubMed

CHOEP-14

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 Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Pfreundschuh et al. 2004 (NHL-B1) 1993-2000 Phase 3 (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 3 (E-esc) 1. CHOEP-21
2. CHOP-21
3. CHOP-14 		Did not meet primary endpoint of EFS Seems more toxic

Chemotherapy

Glucocorticoid therapy

Supportive therapy

  • Filgrastim (Neupogen) by the following weight-based criteria:
    • 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

  • NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm) received: RT consolidation x 36 Gy 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 dosing details in manuscript 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 dosing details in manuscript 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 dosing details in manuscript 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 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 dosing details in abstract PubMed

CHOEP-21

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 Dates of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Köppler et al. 1991 NR Phase 3 (C) hCHOP/IVEP
Kaiser et al. 2002 1990-1997 Phase 3 (C) CHOEP, then BEAM with auto HSCT Did not meet primary endpoint of OS
Pfreundschuh et al. 2004 (NHL-B1) 1993-2000 Phase 3 (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 3 (E-esc) 1. CHOEP-14
2. CHOP-21
3. CHOP-14 		Did not meet primary endpoint of EFS Seems more toxic
Pfreundschuh et al. 2007 (DSHNHL-1999-2) 2000-2003 Phase 3 (C) High CHOEP-21 Did not meet primary endpoint of EFS36 Less toxic

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 4 to 6 cycles, next cycle to start as long as WBC is >2.5 and platelets >80

Subsequent treatment

  • NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm) received: RT consolidation x 36 Gy 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. 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
  3. 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 dosing details in manuscript PubMed
  4. 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 dosing details in manuscript 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 dosing details in manuscript 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 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 dosing details in abstract PubMed
  6. DSHNHL-1999-2: Pfreundschuh M, Zwick C, Zeynalova S, Dührsen U, Pflüger KH, Vrieling T, Mesters R, Mergenthaler HG, Einsele H, Bentz M, Lengfelder E, Trümper L, Rübe C, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II - Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Ann Oncol. 2008 Mar;19(3):545-52. Epub 2007 Dec 6. link to original article contains dosing details in manuscript PubMed NCT00053768

CHOP

CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen variant #1, 3 cycles, prednisone 40 mg/m2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Link et al. 1990 1983-1987 Phase 3 (E-de-esc) CHOP & RT Did not meet primary endpoint of DFS

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

Glucocorticoid therapy

  • 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 Dates of enrollment Evidence Comparator Comparative Efficacy
Miller et al. 1998 (SWOG S8736) 1988-1995 Phase 3 (E-switch-ooc) See link See link
Reyes et al. 2005 (LNH 93-01) 1993-2000 Phase 3 (C) ACVBP Inferior OS
Persky et al. 2014 (SWOG S0313) 2004-2008 Phase 2

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

Glucocorticoid therapy

21-day cycle for 3 cycles

Subsequent treatment

  • SWOG S0313: IFRT, then ibritumomab tiuxetan consolidation
  • SWOG S8736 & LNH 93-01: IFRT consolidation, 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 Dates of enrollment Evidence
Tondini et al. 1993 1985-1990 Phase 2
Bonnet et al. 2007 1993-2002 Non-randomized part of RCT

Chemotherapy

Glucocorticoid therapy

21-day cycle for 4 cycles

Subsequent treatment


Regimen variant #4, 6 cycles, 100 mg prednisone

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pfreundschuh et al. 2004 (NHL-B1) 1993-2000 Phase 3 (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 3 (C) 1. CHOEP-14 Did not meet primary endpoint of EFS
2. CHOEP-21 Did not meet primary endpoint of EFS
3. CHOP-14 Inferior OS
Verdonck et al. 2007 (HOVON-26) 1994-2004 Phase 3 (C) I-CHOP Did not meet primary endpoint of OS
Fridrik et al. 2009 (AGMT NHL-5) 1995-2001 Phase 3 (C) CEOP/IMVP-Dexa Inferior OS

Preceding treatment

Chemotherapy

Glucocorticoid therapy

Supportive therapy

  • Per NHL-B1 and NHL-B2: At the discretion of ordering physician: 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

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 consolidation x 36 Gy to areas of initial bulky disease


Regimen variant #5, 6 cycles, 50 mg/m2 prednisone

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Sonneveld et al. 1995 1988-1993 Phase 3 (C) CNOP Seems to have superior OS

Chemotherapy

Glucocorticoid therapy

28-day cycle for 6 cycles


Regimen variant #6, 6 to 8 cycles

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Zinzani et al. 1995 1991-1993 Phase 3 (C) CIOP Did not meet efficacy endpoints
Habermann et al. 2006 (ECOG E4494) 1998-2001 Phase 3 (C) R-CHOP Seems to have inferior FFS

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 6 to 8 cycles

Subsequent treatment


Regimen variant #7, 8 cycles, 40 mg/m2 prednisone

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Tilly et al. 2003 1993-1998 Phase 3 (C) ACVBP Seems to have inferior OS
Coiffier et al. 2002 (LNH 98-5) 1998-2000 Phase 3 (C) R-CHOP Inferior OS

Chemotherapy

Glucocorticoid therapy

Supportive therapy

  • 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 Dates of enrollment Evidence Comparator Comparative Efficacy
McKelvey et al. 1976 1972-1974 Phase 3 (E-esc) HOP Did not meet endpoint of OS
Elias et al. 1978 1974-1977 Non-randomized
Gordon et al. 1992 1984-1988 Phase 3 (C) m-BACOD Did not meet endpoint of OS
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) 1986-1991 Phase 3 (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 3 (C) CHOP x 3, then HDT with auto HSCT Did not meet primary endpoint of EFS
Miller et al. 1998 (SWOG S8736) 1988-1995 Phase 3 (C) CHOP x 3, then RT Seems to have inferior OS
Jerkeman et al. 1999 1989-1994 Phase 3 (C) MACOP-B Did not meet primary endpoint of OS
Betticher et al. 2006 (MISTRAL) 1997-2003 Phase 3 (C) SHiDo Did not meet primary endpoint of OS
Ohmachi et al. 2010 (JCOG 9809) 1999-2002 Phase 3 (C) CHOP-14 Did not meet primary endpoint of PFS

Note: McKelvey et al. 1976 gave CHOP for 3 cycles past CR.

Chemotherapy

Glucocorticoid therapy

21-day cycle for 8 cycles


Regimen variant #9, 8 cycles, uncapped vincristine, 100 mg prednisone

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gams et al. 1985 1977-1981 Phase 3 (E-switch-ic) BCOP Might have superior OS

Chemotherapy

Glucocorticoid therapy

21-day cycle for 8 cycles


Regimen variant #10, 8 cycles, uncapped vincristine, 100 mg/m2 prednisone

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Milpied et al. 2004 (GOELAMS 072) 1994-1999 Phase 3 (C) CEEP, then CYM, then BEAM with auto HSCT Seems to have inferior EFS

Chemotherapy

Glucocorticoid therapy

21-day cycle for 8 cycles


Regimen variant #11, other

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Andersen et al. 1990 1983-1985 Phase 3 (C) CisEBP Superior CR rate

Chemotherapy

Glucocorticoid therapy

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. link to original article contains dosing details in manuscript 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 dosing details in manuscript PubMed
  3. 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
  4. Link MP, Donaldson SS, Berard CW, Shuster JJ, Murphy SB; POG. Results of treatment of childhood localized non-Hodgkin's lymphoma with combination chemotherapy with or without radiotherapy. N Engl J Med. 1990 Apr 26;322(17):1169-74. link to original article contains dosing details in manuscript PubMed
  5. Andersen J, Thorling K, Bentzen SM, Brincker H, Christensen BE, Pedersen M; Danish Lymphoma Study Group. Phase III trial of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) versus cisplatin, etoposide, bleomycin and prednisone (CisEBP) for the treatment of advanced non-Hodgkin's lymphoma of high grade malignancy. Acta Oncol. 1990;29(8):995-9. link to original article PubMed
  6. 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
  7. 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 contains dosing details in manuscript PubMed
  8. 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: 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
  9. 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
  10. Verdonck LF, van Putten WL, Hagenbeek A, Schouten HC, Sonneveld P, van Imhoff GW, Kluin-Nelemans HC, Raemaekers JM, van Oers RH, Haak HL, Schots R, Dekker AW, de Gast GC, Löwenberg B. Comparison of CHOP chemotherapy with autologous bone marrow transplantation for slowly responding patients with aggressive non-Hodgkin's lymphoma. N Engl J Med. 1995 Apr 20;332(16):1045-51. link to original article contains dosing details in manuscript PubMed
  11. Zinzani PL, Martelli M, Storti S, Musso M, Cantonetti M, Leone G, Cajozzo A, Papa G, Iannitto E, Perrotti A, Bendandi M, Gherlinzoni F, Gentilini P, Rossi G, Aitini E, Mandelli F, Tura S. Phase III comparative trial using CHOP vs CIOP in the treatment of advanced intermediate-grade non-Hodgkin's lymphoma. Leuk Lymphoma. 1995 Oct;19(3-4):329-35. link to original article PubMed
  12. 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 dosing details in manuscript PubMed
  13. 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 dosing details in manuscript PubMed NCT00005089
    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 link to PMC article PubMed
  14. Jerkeman M, Anderson H, Cavallin-Ståhl E, Dictor M, Hagberg H, Johnson A, Kaasa S, Kvaløy S, Sundström C, Akerman M; Nordic Lymphoma Group. CHOP versus MACOP-B in aggressive lymphoma--a Nordic Lymphoma Group randomised trial. Ann Oncol. 1999 Sep;10(9):1079-86. link to original article does not contain dosing details PubMed
  15. 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 dosing details in manuscript 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 dosing details in abstract 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 dosing details in manuscript link to PMC article 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. 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
  16. 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 dosing details in manuscript PubMed
  17. 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 dosing details in manuscript PubMed
  18. 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 dosing details in manuscript PubMed
  19. 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 dosing details in manuscript PubMed
  20. ECOG E1484: 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
  21. 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
  22. 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 dosing details in manuscript 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 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 dosing details in abstract PubMed
  23. 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 dosing details in manuscript PubMed NCT00003150
  24. 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 NCT00003215
  25. 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 dosing details in manuscript PubMed
  26. 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 dosing details in manuscript PubMed
  27. 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
  28. 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 dosing details in manuscript PubMed NCT00133302
  29. 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 dosing details in manuscript link to PMC article PubMed NCT00070018

CHOP (Prednisolone)

CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Burton et al. 2006 (BNLI CHOPVPMITCEBO-GOODRISK) 1997-1999 Phase 3 (C) PMitCEBO Did not meet primary endpoint of FFS

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 to 8 cycles

References

  1. BNLI CHOPVPMITCEBO-GOODRISK: 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 contains dosing details in manuscript PubMed NCT00005867

CHOP-14

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 Dates of enrollment Evidence
Blayney et al. 2003 (SWOG 9349) 1994-1997 Phase 2

Chemotherapy

Glucocorticoid therapy

Supportive therapy

14-day cycle for up to 6 cycles


Regimen variant #2

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Verdonck et al. 2007 (HOVON-26) 1994-2004 Phase 3 (E-esc) CHOP-21 Did not meet primary endpoint of OS

Chemotherapy

Glucocorticoid therapy

Supportive therapy

14-day cycle for 6 cycles


Regimen variant #3

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pfreundschuh et al. 2004 (NHL-B1) 1993-2000 Phase 3 (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 3 (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

Chemotherapy

Glucocorticoid therapy

Supportive therapy

  • (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

  • RICOVER-60, patients with "Initial bulky disease" (lymphoma masses or conglomerates with a diameter of at least 7.5 cm or extranodal involvement): RT consolidation x 36 Gy to areas of initial bulky disease


Regimen variant #4

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Pfreundschuh et al. 2008 (RICOVER-60) 2000-2005 Phase 3 (E-esc) 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

Glucocorticoid therapy

Supportive therapy

  • 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

  • RICOVER-60, patients with "Initial bulky disease" (lymphoma masses or conglomerates with a diameter of at least 7.5 cm or extranodal involvement): RT consolidation x 36 Gy to areas of initial bulky disease

References

  1. 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 dosing details in manuscript 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 dosing details in manuscript 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 PubMed
  4. 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 dosing details in manuscript PubMed
  5. 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 dosing details in manuscript PubMed NCT00052936

CHOP Modified

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

Regimen

Study Dates of enrollment Evidence
Link et al. 1997 1983-1991 Non-randomized part of RCT

Note: This regimen has some major differences from standard CHOP.

Chemotherapy

Glucocorticoid therapy

9-week course

References

  1. 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)

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Bessell et al. 2003 (CLG NH 3003) 1993-2000 Phase 3 (E-switch-ic) MCOP Not designed to look at efficacy

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

Chemotherapy

Glucocorticoid therapy

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 dosing details in manuscript PubMed NCT00002576

CHOP-BCG

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Jones et al. 1979 1974-1977 Phase 3 (E-esc) 1. CHOP-B Not reported
2. COP-Bleo Might have superior CR rate

Chemotherapy

Glucocorticoid therapy

Immunotherapy

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; 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 dosing details in manuscript PubMed
    1. 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. link to original article PubMed

CHOP-B

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 Dates of enrollment Evidence Comparator Comparative Efficacy
Rodriguez et al. 1977 1973-1975 Phase 2
Skarin et al. 1977 1973-1975 Phase 2
Jones et al. 1979 1974-1977 Phase 3 (E-esc) 1. CHOP-BCG Not reported
2. COP-Bleo Might have superior CR rate
Newcomer et al. 1982 NR in abstract Randomized, fewer than 20 patients (E-de-esc) ACOMLA Seems to have superior RFS
Bajetta et al. 1988 1976-1984 Phase 3 (E-esc) CVP Seems to have superior FFFP
Meyer et al. 1993 1982-1989 Phase 3 (C) esc-BACOP Did not meet efficacy endpoints

Chemotherapy

Glucocorticoid therapy

21-day cycle for 8 cycles

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; 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 dosing details in manuscript PubMed
    1. 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. link to original article 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. 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
  6. 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

CHVP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vumon (Teniposide), Prednisone
CHVmP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vm26 (Teniposide), Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Burgers et al. 1983 (EORTC 20751) 1975-1980 Phase 3 (C) CVP Not reported
Carde et al. 1991 1980-1986 Phase 3 (C) CHVmP-VB Inferior OS

Chemotherapy

Glucocorticoid therapy

References

  1. 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
  2. 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 dosing details in abstract PubMed

CHVmP-VB

CHVmP-VB: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vm26 (Teniposide), Prednisone, Vincristine, Bleomycin

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Carde et al. 1991 1980-1986 Phase 3 (E-esc) CHVP Superior OS
Somers et al. 1994a 1986-1991 Phase 3 (C) ProMACE-MOPP Inferior ORR

Chemotherapy

Glucocorticoid therapy

References

  1. 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 dosing details in abstract PubMed
  2. 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 dosing details in manuscript PubMed

C-MOPP

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

Regimen

Study Dates of enrollment Evidence Efficacy
DeVita et al. 1975 1965-1972 Phase 2
Stein et al. 1974 1970-1973 Phase 3 (E-esc) Vincristine & Prednisone (VP)

Chemotherapy

Glucocorticoid therapy

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

CNOP: Cyclophosphamide, Novantrone (Mitoxantrone), Oncovin (Vincristine), Prednisone
MCOP: Mitoxantrone, Cyclophosphamide, Oncovin (Vincristine), Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Sonneveld & Michiels 1990 NR Phase 2
Pavlovsky et al. 1992a 1985-1988 Phase 3 (E-switch-ic) CHOP Did not meet endpoint of OS

Chemotherapy

Glucocorticoid therapy

28-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 link to PMC article contains dosing details in manuscript 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, 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
    1. 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)

CNOP: Cyclophosphamide, Novantrone (Mitoxantrone), Oncovin (Vincristine), Prednisolone
MCOP: Mitoxantrone, Cyclophosphamide, Oncovin (Vincristine), Prednisolone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Bessell et al. 2003 (CLG NH 3003) 1993-2000 Phase 3 (E-switch-ic) Modified CHOP Not designed to look at efficacy

Chemotherapy

Glucocorticoid therapy

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 dosing details in manuscript PubMed NCT00002576

COMP

COMP: Cyclophosphamide, Oncovin (Vincristine), Methotrexate, Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Anderson et al. 1983 1977-1979 Phase 3 (E-de-esc) LSA2-L2 Did not meet primary endpoint of FFS

Chemotherapy

Glucocorticoid therapy

  • 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 therapy, prophylaxis

One course

Subsequent treatment

References

  1. 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 dosing details in manuscript PubMed

COP-Bleo

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Coltman et al. 1977 1966-1974 Non-randomized
Jones et al. 1979 1974-1977 Phase 3 (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

Glucocorticoid therapy

References

  1. 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
  2. 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 dosing details in manuscript PubMed
    1. 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. link to original article PubMed

CVP

CVP: Cyclophosphamide, Vincristine, Prednisone
COP: Cyclophosphamide, Oncovin (Vincristine), Prednisone
VCP: Vincristine, Cyclophosphamide, Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Hoogstraten et al. 1969 NR Phase 3 (E-esc) Cyclophosphamide Superior CR rate
Bagley et al. 1972 1967-1970 Phase 2
Benjamin et al. 1976 1970-1973 Randomized, fewer than 20 pts (E-de-esc) MOPP Not reported
Monfardini et al. 1977 1972-1974 Phase 3 (C) ABP Did not meet endpoint of ORR
Bajetta et al. 1988 1976-1984 Phase 3 (C) BACOP Seems to have inferior FFFP

Chemotherapy

Glucocorticoid therapy

21-day cycles

References

  1. 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
  2. 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
  3. 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
  4. Monfardini S, Tancini G, De Lena 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
  5. 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

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

Regimen

Study Dates of enrollment Evidence
Wilson et al. 2002 1993-1999 Phase 2

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 6 to 8 cycles; begin new cycle every 21 days if ANC greater than 1000/μL 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.

Dose and schedule modifications

  • Start cycle 1 as described above.
  • Obtain CBCs twice per week for nadir measurements.
  • If nadir ANC greater than 500/μL, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
  • If nadir ANC less than 500/μL on 1 or 2 measurements, use same doses as last cycle.
  • If nadir ANC less than 500/μL 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.

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 dosing details in manuscript PubMed

DICEP

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

Regimen

Study Dates of enrollment Evidence
Stewart et al. 2006 1998-2004 Phase 2

Preceding treatment

Chemotherapy

Subsequent treatment

References

  1. 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 dosing details in abstract PubMed content property of HemOnc.org

F-MACHOP

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

Regimen

Study Dates of enrollment Evidence
Amadori et al. 1985 NR in abstract Non-randomized
Infanti et al. 1996 1991-1996 Non-randomized

Chemotherapy

Glucocorticoid therapy

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. link to original article 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

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
McKelvey et al. 1976 1972-1974 Phase 3 (E-de-esc) CHOP Did not meet endpoint of OS
Laver et al. 2001 (POG 8615) 1986-1991 Phase 3 (C) ACOP Did not meet primary endpoint of EFS
Laver et al. 2005 (POG 9315) 1994-2000 Non-randomized part of RCT

Chemotherapy

Glucocorticoid therapy

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. link to original article PubMed
  2. 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
  3. 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 NCT00002618

LD-ACOP-B

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

Regimen

Study Dates of enrollment Evidence
O'Reilly et al. 1991 1983-1985 Non-randomized

Chemotherapy

Glucocorticoid therapy

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

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

Regimen

Study Dates 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 3 (E-esc) 1. CHOP
2. m-BACOD
3. ProMACE-CytaBOM 		Did not meet endpoint of OS
Sertoli et al. 1994 1987-1991 Phase 3 (E-switch-ic) ProMACE-MOPP Did not meet endpoint of OS36
Gianni et al. 1997 1987-NR Phase 3 (C) High-dose sequential therapy Inferior EFS

Chemotherapy

Glucocorticoid therapy

CNS therapy, prophylaxis

Supportive therapy

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. 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: 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
  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 dosing details in manuscript 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 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 dosing details in abstract PubMed

m-BACOD

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

Regimen

Study Dates 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 3 (C) m-BNCOD Did not meet endpoints of OS/RFS
Gordon et al. 1992 1984-1988 Phase 3 (E-esc) CHOP Did not meet endpoint of OS
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) 1986-1991 Phase 3 (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 3 (C) ACVBP Did not meet primary endpoint of FFS

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 10 cycles

Dose and schedule modifications

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

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. 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
  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 dosing details in manuscript PubMed
  4. 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
  5. 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: 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
  6. 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

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Gherlinzoni et al. 1990 1984-1986 Phase 3 (E-switch-ic) m-BACOD Did not meet endpoints of OS/RFS

Chemotherapy

Glucocorticoid therapy

References

  1. 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

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

Regimen

Study Dates of enrollment Evidence
O'Reilly et al. 1993 1988-1991 Phase 2

Note: 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).

Glucocorticoid therapy

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 dosing details in manuscript PubMed

PACEBOM

PACEBOM: Prednisolone, Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Bleomycin, Oncovin (Vincristine), Methotrexate

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Linch et al. 2000 1987-1991 Phase 3 (E-esc) CHOP Might have superior cause-specific survival

Note: the text suggests that this is an 11-week protocol, but table 1 indicates it to be 12 weeks.

Glucocorticoid therapy

Chemotherapy

7-day cycle for 12 cycles (see note)

References

  1. 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 contains dosing details in manuscript PubMed

PEN

PEN: Prednisone, Etoposide, Novantrone (Mitoxantrone)

Regimen

Study Dates of enrollment Evidence
Goss et al. 1995 1991-1993 Phase 2

Glucocorticoid therapy

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

PMitCEBO: Prednisolone, Mitoxantrone, Cyclophosphamide, Etoposide, Bleomycin, Oncovin (Vincristine)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Mainwaring et al. 2001 1993-1997 Phase 3 (E-switch-ic) PAdriaCEBO Superior OS
Burton et al. 2006 (BNLI CHOPVPMITCEBO-GOODRISK) 1997-1999 Phase 3 (E-esc) CHOP Did not meet primary endpoint of FFS
Pfreundschuh et al. 2006 (NCIC-CTG LY.9) 2000-2003 Phase 3 (C) 1a. R-CHOP
1b. R-CHOEP
1c. R-MACOP-B
1d. R-PMitCEBO 		Inferior EFS1

1Reported efficacy is based on the 2011 update.

Glucocorticoid therapy

  • Prednisolone (Millipred) as follows:
    • Cycles 1 to 4: 50 mg PO once per day on days 1 to 7
    • Cycles 5 up to 16: 50 mg PO once every other day

Chemotherapy

7-day cycle up to 16 cycles

References

  1. Mainwaring PN, Cunningham D, Gregory W, Hoskin P, Hancock B, Norton AJ, MacLennan K, Smith P, Vaughan Hudson G, 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
  2. BNLI CHOPVPMITCEBO-GOODRISK: 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 contains dosing details in manuscript PubMed NCT00005867
  3. 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 dosing details in manuscript PubMed NCT00064116
    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 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 dosing details in abstract PubMed

ProMACE-CytaBOM

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Longo et al. 1991 1981-1988 Phase 3 (E-switch-ic) ProMACE-MOPP Seems to have superior OS
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) 1986-1991 Phase 3 (E-esc) 1. CHOP
2. MACOP-B
3. m-BACOD 		Did not meet endpoint of OS

Glucocorticoid therapy

Chemotherapy

Supportive therapy

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

CNS therapy, prophylaxis

  • Patients with initial bone or bone marrow involvement who achieved a CR were treated with 2400 cGy prophylactic cranial irradiation.

Dose and schedule modifications

  • "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"

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 dosing details in manuscript PubMed
  2. 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: 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

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fisher et al. 1983 1977-1981 Non-randomized
Longo et al. 1991 1981-1988 Phase 3 (C) ProMACE-CytaBOM Seems to have inferior OS
Somers et al. 1994a 1986-1991 Phase 3 (E-switch-ic) CHVmP-VB Superior ORR
Sertoli et al. 1994 1987-1991 Phase 3 (C) MACOP-B Did not meet endpoint of OS36

Chemotherapy

Glucocorticoid therapy

References

  1. 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
  2. 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
  3. 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
  4. 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 does not contain dosing details PubMed

R-CHMP

R-CHMP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Marqibo (Vincristine liposomal), Prednisone

Regimen variant #1, 3 cycles

Study Dates of enrollment Evidence
Hagemeister et al. 2013 2001-2002 Phase 2

Note: This regimen was intended for stage I patients with no LN greater than 5 cm.

Targeted therapy

Chemotherapy

Glucocorticoid therapy

21-day cycle for 3 cycles

Subsequent treatment

  • RT consolidation


Regimen variant #2, 6 cycles

Study Dates of enrollment Evidence
Hagemeister et al. 2013 2001-2002 Phase 2

Targeted therapy

Chemotherapy

Glucocorticoid therapy

21-day cycle for 6 cycles

References

  1. Hagemeister F, Rodriguez MA, Deitcher SR, Younes A, Fayad L, Goy A, Dang NH, Forman A, McLaughlin P, Medeiros LJ, Pro B, Romaguera J, Samaniego F, Silverman JA, Sarris A, Cabanillas F. Long term results of a phase 2 study of vincristine sulfate liposome injection (Marqibo(®) ) substituted for non-liposomal vincristine in cyclophosphamide, doxorubicin, vincristine, prednisone with or without rituximab for patients with untreated aggressive non-Hodgkin lymphomas. Br J Haematol. 2013 Sep;162(5):631-8. Epub 2013 Jun 27. link to original article contains dosing details in manuscript PubMed

VABE

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

Regimen

Study Dates of enrollment Evidence
O'Reilly et al. 1991 1983-1985 Non-randomized

Chemotherapy

Glucocorticoid therapy

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

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

Regimen

Study Dates of enrollment Evidence
Pichert et al. 1992 Retrospective
Martelli et al. 1993 1988-1990 Phase 2

Chemotherapy

Glucocorticoid therapy

References

  1. 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
  2. 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

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

Regimen

Study Dates of enrollment Evidence
Bernard et al. 2005 1984-1996 Phase 2

Chemotherapy

Glucocorticoid therapy

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; 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

VEPA: Vincristine, Endoxan (Cyclophosphamide), Prednisolone, Adriamycin (Doxorubicin)

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Shimoyama et al. 1988 (JCOG8101) 1981-1983 Phase 3 (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

Glucocorticoid therapy

References

  1. 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

VNCOP-B: Vepesid (Etoposide), Novantrone (Mitoxantrone), Cyclophosphamide, Oncovin (Vincristine), Prednisone, Bleomycin

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Zinzani et al. 1997 1993-1995 Phase 3 (C) VNCOP-B & G-CSF Did not meet endpoint of RFS
Zinzani et al. 2002 1996-2001 Phase 3 (C) VNCOP-B & G-CSF x 12 wk Did not meet endpoint of RFS60

Chemotherapy

Glucocorticoid therapy

References

  1. 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
  2. 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

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 Dates of enrollment Evidence Comparator Comparative Efficacy
Ruan et al. 2010 (Cornell 0309006313) 2004-2007 Phase 2
Leonard et al. 2017 (C05013) 2009-2013 Randomized Phase 2 (E-esc) R-CHOP Did not meet primary endpoint of PFS

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 6 cycles

References

  1. Cornell 0309006313: 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 dosing details in manuscript PubMed NCT00151320
  2. 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 dosing details in manuscript PubMed NCT00931918
  3. 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

Cy/TBI: Cyclophosphamide & Total Body Irradiation

Regimen

Study Dates of enrollment Evidence
Takvorian et al. 1987 1982-1987 Non-randomized

Chemotherapy

Radiotherapy

References

  1. 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

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Velasquez et al. 1988 1984-1986 Phase 2
Philip et al. 1995 (PARMA) 1987-1994 Phase 3 (C) DHAP x 2, then BEAC Seems to have inferior OS
Josting et al. 2005 NR Phase 2

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.

Glucocorticoid therapy

Chemotherapy

  • Cytarabine (Ara-C) by the following age-based criteria:
    • Younger than 70 years old: 2000 mg/m2 IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m2)
    • Older than 70 years old: 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 therapy

3- to 4-week cycle for 2 cycles (PARMA & Josting et al. 2005) or up to 10 cycles (see note)

Subsequent treatment

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 dosing details in manuscript 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 dosing details PubMed
  3. 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 dosing details in abstract PubMed

EPIC regimen

EPIC: Etoposide, Prednisolone, Ifosfamide, Carboplatin

Regimen

Study Dates of enrollment Evidence
Hickish et al. 1993 1989-1991 Phase 2
Richardson et al. 1994 1991-1993 Phase 2, fewer than 20 patients

Chemotherapy

Glucocorticoid therapy

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 original article 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. link to original article PubMed

HAM

HAM: High-dose Ara-C (Cytarabine) & Mitoxantrone
NOAC: NOvantrone (Mitoxantrone) & Ara-C (Cytarabine)

Regimen

Study Dates of enrollment Evidence
Ho et al. 1989 1986-1987 Phase 2

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. link to original article PubMed

MINE

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

Regimen

Study Dates of enrollment Evidence
Rodriguez et al. 1995 NR Phase 2

Chemotherapy

Supportive therapy

  • 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 (see below)

Subsequent treatment

  • Rodriguez et al. 1995, CR: A total of 6 cycles of MINE, then ESHAP consolidation x 3
  • Rodriguez et al. 1995, PR: 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 dosing details in manuscript PubMed

VIM

VIM: Vepesid (Etoposide), Ifosfamide, Mitoxantrone

Regimen

Study Dates of enrollment Evidence
Hopfinger et al. 1995 1986-1992 Phase 2

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. link to original article PubMed

VIPD

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

Regimen

Study Dates of enrollment Evidence
Haim et al. 1992 1989-1991 Phase 2

Glucocorticoid therapy

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. link to original article PubMed

Consolidation after salvage therapy

ESHAP

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

Regimen

Study Dates of enrollment Evidence
Rodriguez et al. 1995 NR Phase 2

Preceding treatment

  • MINE salvage induction

Chemotherapy

Glucocorticoid therapy

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 dosing details in manuscript PubMed

Relapsed or refractory, further lines of therapy

CEPP(B)

CEPP(B): Cyclophosphamide, Etoposide, Procarbazine, Prednisone, (optional) Bleomycin

Regimen

Study Dates of enrollment Evidence
Chao et al. 1990 1982-1989 Phase 2

Chemotherapy

Glucocorticoid therapy

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

DICE: Dexamethasone, Ifosfamide, Carboplatin, Etoposide

Regimen

Study Dates of enrollment Evidence
Goss et al. 1991 NR Phase 2
Coleman et al. 2001 NR in abstract Phase 2

Glucocorticoid therapy

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. link to original article 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. 2001 Jul;64:41-5. PubMed

DICEP

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

Regimen

Study Dates of enrollment Evidence
Neidhart et al. 1994 1987-1991 Phase 2

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. link to original article PubMed

EPOCH

EPOCH: Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
CHEOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Etoposide, Oncovin (Vincristine), Prednisone

Regimen

Study Dates of enrollment Evidence Efficacy
Wilson et al. 1993 1990-1992 Phase 2 ORR: 87%

Chemotherapy

Glucocorticoid therapy

Supportive therapy

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 dosing details in manuscript PubMed
    1. 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

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

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Velasquez et al. 1994 1986-1988 Phase 3 (E-esc) ESHA Superior RR
Avilés et al. 2010 NR Phase 3 (C) R-ESHAP Did not meet efficacy endpoints

Note: timing of cycle was variable and dependent on "recovery of the toxic effects"

Chemotherapy

Glucocorticoid therapy

Supportive therapy

  • 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

  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 dosing details in manuscript 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

Etoposide, Ifosfamide, Methotrexate

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

Regimen

Study Dates of enrollment Evidence
Cabanillas et al. 1982 NR Phase 2

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

GDP

GDP: Gemcitabine, Dexamethasone, Platinol (Cisplatin)

Regimen

Study Dates of enrollment Evidence
Crump et al. 2004 2001-2002 Phase 2

Chemotherapy

Glucocorticoid therapy

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; 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

ICE: Ifosfamide, Carboplatin, Etoposide

Regimen variant #1, inpatient

Study Dates of enrollment Evidence
Moskowitz et al. 1999 1993-1997 Phase 2
Zelenetz et al. 2003 1993-2000 Phase 2

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

Chemotherapy

  • Ifosfamide (Ifex) 5000 mg/m2 IV continuous infusion over 24 hours, started on day 2, mixed with mesna
  • 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 therapy

  • Mesna (Mesnex) 5000 mg/m2 IV continuous infusion over 24 hours, started on day 2, mixed with ifosfamide
  • 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/μL and platelet count greater than 50 x 109/L


Regimen variant #2, outpatient

Study Dates of enrollment Evidence
Hertzberg et al. 2003 NR Phase 2, fewer than 20 pts in this subgroup

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

Chemotherapy

Supportive therapy

21-day cycle for 3 cycles

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 contains dosing details in manuscript 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 dosing details in manuscript 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 contains dosing details in manuscript PubMed

R-INO

R-INO: Rituximab, INOtuzumab ozogamicin

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Fayad et al. 2013 (B1931004) 2006-NR Phase 1/2
Dang et al. 2017 (B1931008) 2011-2013 Phase 3 (E-switch-ooc) Investigator's choice of:
1a. BR
1b. Gemcitabine & Rituximab 		Did not meet primary endpoint of OS
Median OS: 9.5 vs 9.5 mo
(HR 1.1, 95% CI 0.8-1.4)

Targeted therapy

Antibody-drug conjugate therapy

28-day cycle for up to 8 cycles

References

  1. 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 dosing details in manuscript PubMed NCT00299494
  2. 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 dosing details in abstract PubMed NCT01232556
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