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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main DLBCL page for current regimens.
Last updated on 2024-07-23:69 regimens on this page
89 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====
*Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
*Bleomycin (Blenoxane) 15 mg/m2 IV once per day on days 1 & 8
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg/m2 IM once per day on days 1 to 5
21-day cycle for at least 6 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==ACEP==
ACEP: Adriamycin (Doxorubicin), Cyclophosphamide, Etoposide, Prednisone
===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====
*Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once per day on days 1 & 2
*Etoposide (Vepesid) as follows:
**Cycles 2 to 4: 150 mg/m2 IV once per day on days 1 to 3
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2 (route not specified) once per day on days 1 to 5
====CNS therapy, prophylaxis====
*Methotrexate (MTX) 15 mg IT once on day 2
====Supportive therapy====
*G-CSF 5 mcg/kg/day SC on days 6 to 13
14-day cycle for 4 cycles
===References===
# Dumontet C, Thieblemont C, Espinouse D, Bouafia F, Hequet O, Salles G, Coiffier B. A prospective study of intensive induction therapy with high-dose consolidation in patients with aggressive non-Hodgkin's lymphoma and two or three adverse prognostic factors. Leukemia. 2000 Dec;14(12):2159-65. link to original article EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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	Not reported in abstract	Randomized, fewer than 20 patients	CHOP-B 	Seems to have shorter RFS
Note: The full manuscript was not available for review.
====Chemotherapy====
*Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once per day on days 1, 8, 15
*Methotrexate (MTX) 120 mg/m2 IV once per day on days 22, 29, 36, 43, 50, 57, 71
*Cytarabine (Ara-C) 300 mg/m2 IV once per day on days 22, 29, 36, 43, 50, 57, 71
90-day cycle for 3 cycles
===References===
# Newcomer LN, Cadman EC, Nerenberg MI, Chen M, Bertino JR, Farber LR, Prosnitz LR. Randomized study comparing doxorubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, and cytarabine (ACOMLA) with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-B) in the treatment of diffuse histiocytic lymphoma. Cancer Treat Rep. 1982 Jun;66(6):1279-84. EuroPMC
==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 longer 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	Longer OS (secondary endpoint)OS60: 90% vs 81%Longer EFS (primary endpoint)
Haioun et al. 2009 (LNH 98-3) 	1999-2004 	Phase 3 (C) 	ACEP 	Did not meet endpoint of OS
Ketterer et al. 2013 (LNH03-1B)	2003-2008 	Phase 3 (C) 	R-ACVBP 	Shorter PFSPFS36: 83% vs 95%(HR 2.70, 95% CI 1.12-6.67)
===Induction===
====Chemotherapy====
*Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
*Vindesine (Eldisine) 2 mg/m2 IV once per day on days 1 & 5
*Bleomycin (Blenoxane) 10 units IV once per day on days 1 & 5
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
====CNS therapy, prophylaxis====
*Methotrexate (MTX) 15 mg IT on day 2
====Supportive therapy====
*G-CSF or GM-CSF SC once per day on days 6 to 13
21-day cycle for 4 cycles, followed by:
===Consolidation, part 1===
====Chemotherapy====
*Methotrexate (MTX) 3000 mg/m2 IV once on day 1
====Supportive therapy====
*Leucovorin rescue
14-day cycle for 2 cycles, followed in 2 weeks by:
===Consolidation, part 2 (EI)===
====Chemotherapy====
*Etoposide (Vepesid) 300 mg/m2 IV once on day 1
*Ifosfamide (Ifex) 1500 mg/m2 IV once on day 1
====Supportive therapy====
*Mesna (Mesnex) "protection" (details not provided)
14-day cycle for 4 cycles, followed in 2 weeks by:
===Consolidation, part 3===
====Chemotherapy====
*Cytarabine (Ara-C) 100 mg/m2 SC once per day on days 1 to 4
14-day cycle for 2 cycles
===References===
# LNH87-1: Tilly H, Mounier N, Lederlin P, Brière J, Dupriez B, Sebban C, Bosly A, Biron P, Nouvel C, Herbrecht R, Bordessoule D, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte. Randomized comparison of ACVBP and m-BACOD in the treatment of patients with low-risk aggressive lymphoma: the LNH87-1 study. J Clin Oncol. 2000 Mar;18(6):1309-15. link to original article EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 EuroPMC NCT00169169
# 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 EuroPMC
# 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 EuroPMC 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 was referred to as "intensified CHOP-Bleo" in the original manuscript, but bears more resemblance to ACVBP induction and is therefore re-named as ACVBP.
====Chemotherapy====
*Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
*Vindesine (Eldisine) 2 mg/m2 IV once per day on days 1 & 5
*Bleomycin (Blenoxane) 5 mg/m2 IV once per day on days 1 to 5
====Glucocorticoid therapy====
*Methylprednisolone (Solumedrol) 60 mg/m2 (route not specified) once per day on days 1 to 5
====CNS therapy, prophylaxis====
*Methotrexate (MTX) 15 mg IT once
15-day cycle for 3 cycles; cycles were delayed until ANC greater than 1500/μL
====Subsequent treatment====
*CYM consolidation, then CVAP-Bleo intensification
===References===
# LNH-80: Coiffier B, Bryon PA, Berger F, Archimbaud E, Ffrench M, Extra JM, Guyotat D, Fiere D, Gentilhomme O, Magaud JP, Blanc M, Peaud PY, Vuvan H, Viala JJ. Intensive and sequential combination chemotherapy for aggressive malignant lymphomas (protocol LNH-80). J Clin Oncol. 1986 Feb;4(2):147-53. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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 shorter OS
====Chemotherapy====
*Carmustine (BCNU) 100 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
28-day cycle for 6 cycles
===References===
# Gams RA, Rainey M, Dandy M, Bartolucci AA, Silberman H, Omura G; Southeastern Cancer Study Group. Phase III study of BCOP v CHOP in unfavorable categories of malignant lymphoma: a Southeastern Cancer Study Group trial. J Clin Oncol. 1985 Sep;3(9):1188-95. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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====
*Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Procarbazine (Matulane) 100 mg/m2 PO once per day on days 1 to 7
*Bleomycin (Blenoxane) 10 units SC once on day 15
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 15
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 15 to 21
21- to 28-day cycle for up to 9 cycles
===References===
# Laurence J, Coleman M, Allen SL, Silver RT, Pasmantier M. Combination chemotherapy of advanced diffuse histiocytic lymphoma with the six-drug COP-BLAM regimen. Ann Intern Med. 1982 Aug;97(2):190-5. link to original article EuroPMC
# 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 EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==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====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 30 minutes once on day 1
*Pegylated liposomal doxorubicin (Doxil) 30 mg/m2 IV over 60 minutes once on day 1
*Vincristine (Oncovin) 2 mg IV over 15 minutes once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
21-day cycle for 6 to 8 cycles
===References===
# Martino R, Perea G, Caballero MD, Mateos MV, Ribera JM, de Oteyza JP, Arranz R, Terol MJ, Sierra J, San Miguel JF. Cyclophosphamide, pegylated liposomal doxorubicin (Caelyx), vincristine and prednisone (CCOP) in elderly patients with diffuse large B-cell lymphoma: results from a prospective phase II study. Haematologica. 2002 Aug;87(8):822-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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 longer EFS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
*Epirubicin (Ellence) 100 mg/m2 IV once on day 1
*Vindesine (Eldisine) 3 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 80 mg/m2 PO or IV once per day on days 1 to 5
====CNS therapy, prophylaxis====
*Methotrexate (MTX) 15 mg IT once on day 2
*Methylprednisolone (Solumedrol) IT once on day 2
14-day cycle for 2 cycles
====Subsequent treatment====
*GOELAMS 072, patients with at least PR: CYM consolidation, then BEAM with auto HSCT intensification
===References===
# GOELAMS 072: Milpied N, Deconinck E, Gaillard F, Delwail V, Foussard C, Berthou C, Gressin R, Lucas V, Colombat P, Harousseau JL; Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004 Mar 25;350(13):1287-95. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
*Epirubicin (Ellence) 70 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg PO once per day on days 1 to 7
21-day cycles
===References===
# Economopoulos T, Dimopoulos MA, Mellou S, Pavlidis N, Samantas E, Nicolaides C, Tsatalas C, Papadopoulos A, Papageogriou E, Papasavvas P, Fountzilas G. Treatment of intermediate- and high-grade non-Hodgkin's lymphoma using CEOP versus CNOP. Eur J Haematol. 2002 Mar;68(3):135-43. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 EuroPMC
==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====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Epirubicin (Ellence) 75 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
21-day cycle for 6 cycles
===References===
# ALLG NHL07: Hertzberg M, Matthews JP, Stone JM, Dubosq MC, Grigg A, Ellis D, Benson W, Browett P, Horvath N, Januszewicz H, Abdi E, Green M, Bonaventura A, Marlton P, Cannell P, Wolf M; ALLG. A phase III randomized trial of high-dose CEOP + filgrastim versus standard-dose CEOP in patients with non-Hodgkin lymphoma: 10-year follow-up data: Australasian Leukaemia and Lymphoma Group (ALLG) NHL07 trial. Am J Hematol. 2014 May;89(5):536-41. Epub 2014 Feb 21. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==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-212. CHOP-14 	Longer EFS 	Seems more toxic
Pfreundschuh et al. 2004 (NHL-B1)	1993-2000 	Phase 3 (E-esc)	3. CHOEP-21 	Seems to have longer OS 	
Pfreundschuh et al. 2004 (NHL-B2)	1993-2000 	Phase 3 (E-esc)	1. CHOEP-212. CHOP-21 3. CHOP-14	Did not meet primary endpoint of EFS	Seems more toxic
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Filgrastim (Neupogen) by the following weight-based criteria:
**Less than 75 kg: 300 mcg SC once per day on days 4 to 13
**75 kg or more: 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 3600 cGy to extranodal sites of disease when possible
===References===
# NHL-B1: Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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. Epub 2011 Sep 21. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==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 	Not reported 	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-212. CHOP-14 	Longer EFS 	Seems more toxic
Pfreundschuh et al. 2004 (NHL-B1) 	1993-2000 	Phase 3 (E-esc)	3. CHOEP-14 	Seems to have shorter OS 	
Pfreundschuh et al. 2004 (NHL-B2) 	1993-2000 	Phase 3 (E-esc)	1. CHOEP-142. 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====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Filgrastim (Neupogen) by discretion of ordering physician
21-day cycle for 4 to 6 cycles; next cycle to start as long as WBC is >2.5 and platelets >80
====Subsequent treatment====
*NHL-B1, patients with initial bulky disease (mass conglomerate at least 7.5 cm) received: RT consolidation x 3600 cGy to extranodal sites of disease when possible
===References===
# Köppler H, Pflüger KH, Eschenbach I, Pfab R, Birkmann J, Zeller W, Steinhauer EU, Gropp C, Oehl S, Lötzke E, Kuhn H, Drings P, Gossmann HH, Lennert K, Stein H, Havemann K. Sequential versus alternating chemotherapy for high grade non-Hodgkin's lymphomas: a randomized multicentre trial. Hematol Oncol. 1991 Jul-Oct;9(4-5):217-23. link to original article EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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. Epub 2011 Sep 21. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 was a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment. Note some substantial differences from typical CHOP protocols.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.5 mg/m2 IV once on day 1
====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 	Shorter OS
Persky et al. 2014 (SWOG S0313)	2004-2008 	Phase 2 	 	
Note: this was a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV over 1 to 2 minutes once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV over 1 to 2 minutes once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 3 cycles
====Subsequent treatment====
*SWOG S0313: IFRT, then ibritumomab tiuxetan consolidation
*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====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
21-day cycle for 4 cycles
====Subsequent treatment====
*Bonnet et al. 2007: IFRT consolidation x 4000 cGy versus no further 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-142. CHOP-14	Seems to have shorter OS
Pfreundschuh et al. 2004 (NHL-B1)	1993-2000 	Phase 3 (C)	3. CHOEP-21 	Shorter EFS
Pfreundschuh et al. 2004 (NHL-B2)	1993-2000 	Phase 3 (C)	1. CHOEP-14 	Did not meet primary endpoint of EFS
Pfreundschuh et al. 2004 (NHL-B2)	1993-2000 	Phase 3 (C)	2. CHOEP-21 	Did not meet primary endpoint of EFS
Pfreundschuh et al. 2004 (NHL-B2)	1993-2000 	Phase 3 (C)	3. CHOP-14 	Shorter 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 	Shorter OS
====Preceding treatment====
*NHL-B1 and NHL-B2: Vincristine & Prednisone pre-phase
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Per NHL-B1 and NHL-B2: At the discretion of ordering physician: Filgrastim (Neupogen) by the following weight-based criteria:
**Less than 75 kg: 300 mcg SC once per day on days 4 to 13
**75 kg or more: 480 mcg 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 3600 cGy 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 longer OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 50 mg/m2 PO once per day on days 1 to 5
28-day cycle for 6 cycles
===Regimen variant #6, 6 to 8 cycles===
Study 	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 shorter FFS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
====Supportive therapy====
*Filgrastim (Neupogen) "recommended according to guidelines"
21-day cycle for 6 to 8 cycles
====Subsequent treatment====
*ECOG E4494, patients with CR/PR: Rituximab maintenance versus observation
===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 shorter OS
Coiffier et al. 2002 (LNH 98-5)	1998-2000 	Phase 3 (C)	R-CHOP 	Shorter OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
====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
Fisher et al. 1993 (SWOG-8516/Intergroup 0067)	1986-1991 	Phase 3 (C) 	2. m-BACOD 	Did not meet endpoint of OS
Fisher et al. 1993 (SWOG-8516/Intergroup 0067)	1986-1991 	Phase 3 (C) 	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 shorter 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====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV over 1 to 2 minutes once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV over 1 to 2 minutes once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 8 cycles
===Regimen variant #9, 8 cycles, uncapped vincristine, 100 mg prednisone===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Gams et al. 1985	1977-1981 	Phase 3 (E-switch-ic)	BCOP 	Might have longer OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 8 cycles
===Regimen variant #10, 8 cycles, uncapped vincristine, 100 mg/m2 prednisone===
Study 	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 shorter EFS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycle for 8 cycles
===Regimen variant #11, 9 cycles, uncapped vincristine===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Andersen et al. 1990	1983-1985 	Phase 3 (C)	CisEBP 	Higher CR rate
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
28-day cycle for 9 cycles
===References===
# McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
## 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 EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00005089
##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 EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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. Epub 2005 May 2. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
## 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. Epub 2010 Jun 14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
## 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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. Epub 2011 Sep 21. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00003150
# MISTRAL: Betticher DC, Martinelli G, Radford JA, Kaufmann M, Dyer MJ, Kaiser U, Aulitzky WE, Beck J, von Rohr A, Kovascovics T, Cogliatti SB, Cina S, Maibach R, Cerny T, Linch DC. Sequential high dose chemotherapy as initial treatment for aggressive sub-types of non-Hodgkin lymphoma: results of the international randomized phase III trial (MISTRAL). Ann Oncol. 2006 Oct;17(10):1546-52. Epub 2006 Aug 3. link to original article EuroPMC NCT00003215
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00133302
# SWOG S0313: Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. Epub 2014 Nov 13. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
21-day cycle for 6 to 8 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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====
*Cyclophosphamide (Cytoxan) 1600 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 65 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 11, or until ANC is greater than 10,000/μL
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====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 70 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 11
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 	Shorter EFS
Pfreundschuh et al. 2004 (NHL-B1) 	1993-2000 	Phase 3 (E-esc)	2. CHOEP-21 3. CHOP-21	Seems to have longer OS
Pfreundschuh et al. 2008 (RICOVER-60)	2000-2005 	Phase 3 (C) 	1. CHOP-14 x 8 	Seems to have shorter EFS
Pfreundschuh et al. 2008 (RICOVER-60)	2000-2005 	Phase 3 (C) 	2. R-CHOP-14 x 6 	Shorter OS
Pfreundschuh et al. 2008 (RICOVER-60)	2000-2005 	Phase 3 (C) 	3. R-CHOP-14 x 8 	Shorter PFS
====Preceding treatment====
*Vincristine & Prednisone pre-phase (recommended in NHL-B1 and mandatory in RICOVER-60)
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*(per Pfreundschuh et al. 2004):
*Filgrastim (Neupogen) by the following weight-based criteria:
**Less than 75 kg: 300 mcg SC once per day on days 4 to 13
**75 kg or more: 480 mcg 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 3600 cGy 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 longer EFS
Pfreundschuh et al. 2008 (RICOVER-60)	2000-2005 	Phase 3 (E-esc)	2. R-CHOP-14 x 6	Not reported
Pfreundschuh et al. 2008 (RICOVER-60)	2000-2005 	Phase 3 (E-esc)	3. R-CHOP-14 x 8	Not reported
====Preceding treatment====
*Vincristine & Prednisone pre-phase
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Filgrastim (Neupogen) by the following weight-based criteria:
**Less than 75 kg: 300 mcg SC once per day on days 4 to 13
**75 kg or more: 480 mcg 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 3600 cGy to areas of initial bulky disease
===References===
# SWOG 9349: Blayney DW, LeBlanc ML, Grogan T, Gaynor ER, Chapman RA, Spiridonidis CH, Taylor SA, Bearman SI, Miller TP, Fisher RI; SWOG. Dose-intense chemotherapy every 2 weeks with dose-intense cyclophosphamide, doxorubicin, vincristine, and prednisone may improve survival in intermediate- and high-grade lymphoma: a phase II study of the Southwest Oncology Group (SWOG 9349). J Clin Oncol. 2003 Jul 1;21(13):2466-73. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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. Epub 2008 Jan 15. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 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====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once per day on days 1, 22, 43
*Doxorubicin (Adriamycin) 40 mg/m2 IV once per day on days 1, 22, 43
*Vincristine (Oncovin) 1.5 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36, 43
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 28, 43 to 47
9-week course
====Subsequent treatment====
*6-MP & MTX maintenance
===References===
# Link MP, Shuster JJ, Donaldson SS, Berard CW, Murphy SB. Treatment of children and young adults with early-stage non-Hodgkin's lymphoma. N Engl J Med. 1997 Oct 30;337(18):1259-66. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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 was designed for elderly patients and is of lower intensity than standard CHOP.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1 mg IV once on day 1
====Glucocorticoid therapy====
*Prednisolone (Millipred) 20 mg PO twice per day on days 1 to 5
21-day cycle for 6 cycles
===References===
# CLG NH 3003: Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 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
Jones et al. 1979	1974-1977 	Phase 3 (E-esc)	2. COP-Bleo	Might have higher CR rate
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/mg2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/mg2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/mg2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Immunotherapy====
*BCG vaccine 1 ampule SC once per day on days 8 & 15
21- to 28-day cycle for 8 cycles
===References===
# Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Butler JJ, Byrne GE Jr, Moon TE, Fisher R, Haskins CL, Coltman CA Jr; SWOG. Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study. Cancer. 1979 Feb;43(2):417-25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
==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
Jones et al. 1979 	1974-1977 	Phase 3 (E-esc) 	2. COP-Bleo	Might have higher CR rate
Newcomer et al. 1982 	Not reported in abstract	Randomized, fewer than 20 patients (E-de-esc)	ACOMLA 	Seems to have longer RFS
Bajetta et al. 1988 	1976-1984 	Phase 3 (E-esc) 	CVP 	Seems to have longer FFFP
Meyer et al. 1993 	1982-1989 	Phase 3 (C) 	esc-BACOP 	Did not meet efficacy endpoints
Note: The full manuscript for Newcomer et al. 1982 was not available for review.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
*Bleomycin (Blenoxane) 4 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 8 cycles
===References===
# Rodriguez V, Cabanillas F, Burgess MA, McKelvey EM, Valdivieso M, Bodey GP, Freireich EJ. Combination chemotherapy ("CHOP-Bleo") in advanced (non-Hodgkin) malignant lymphoma. Blood. 1977 Mar;49(3):325-33. link to original article EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
# 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. EuroPMC
# 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 EuroPMC
# 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 EuroPMC
==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 	Shorter OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Teniposide (Vumon) 60 mg/m2 IV over 60 minutes once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
21- to 28-day cycle for 8 cycles
===References===
# EORTC 20751: Burgers JM, Somers R, Quasim MM, van Glabbekke M. Report on the EORTC 20751 lymphoma trial. Int J Radiat Oncol Biol Phys. 1983 Jan;9(1):11-5. link to original article EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==CHVmP-VB==
CHVmP-VB: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vm26 (Teniposide), Prednisone, Vincristine, Bleomycin
===Regimen variant #1, BSA-based dosing===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Carde et al. 1991	1980-1986 	Phase 3 (E-esc)	CHVP 	Longer OS
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Teniposide (Vumon) 60 mg/m2 IV over 60 minutes once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 15
*Bleomycin (Blenoxane) 6 mg/m2 IV once on day 15
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
21-day cycle for 8 cycles
===Regimen variant #2, flat dosing===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Somers et al. 1994 (EORTC 20855)	1986-1991 	Phase 3 (C)	ProMACE-MOPP	Lower ORR
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Teniposide (Vumon) 60 mg/m2 IV over 60 minutes once on day 1
*Vincristine (Oncovin) 2 mg IV once on day 15
*Bleomycin (Blenoxane) 10 mg IV once on day 15
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
21-day cycle for 8 cycles
===References===
# Carde P, Meerwaldt JH, van Glabbeke M, Somers R, Monconduit M, Thomas J, de Wolf-Peeters C, de Pauw B, Tanguy A, Kluin-Nelemans JC, Noordijk EM, Regnier R, Bron D, Lustman-Marechal J, Caillou B, Bosq J, van Heerde P, van Unnik JAM, Burgers MV, Hayat M, Cosset JM, van der Schueren E, Wagener J, Hagenbeek A, Cattan A, Duez N, Tubiana M; EORTC Lymphoma Group. Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade non-Hodgkin's lymphoma (NHL): the 1980-1985 EORTC trial. Ann Oncol. 1991 Jun;2(6):431-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# EORTC 20855: 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==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====
*Cyclophosphamide (Cytoxan) 650 mg/m2 IV once per day on days 1 & 8
*Vincristine (Oncovin) 1.4 mg/m2 IV once per day on days 1 & 8
*Procarbazine (Matulane) 100 mg/m2 PO once per day on days 1 to 14
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
28-day cycle for 6 cycles
===References===
# Stein RS, Moran EM, Desser RK, Miller JB, Golomb HM, Ultmann JE. Combination chemotherapy of lymphomas other than Hodgkin's disease. Ann Intern Med. 1974 Nov;81(5):601-8. link to original article EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==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	Not reported 	Phase 2 	 	
Pavlovsky et al. 1992a 	1985-1988 	Phase 3 (E-switch-ic)	CHOP 	Did not meet endpoint of OS1Median OS: 1801 vs 932 d(RR 0.93, 95% CI 0.68-1.27)
1Reported efficacy for Pavlovsky et al. 1992a is based on the 1995 update.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 50 mg/m2 PO once per day on days 1 to 5
21- to 28-day cycle for varying durations: 6 cycles (Sonneveld & Michiels 1990); 6 to 8 cycles (Pavlovsky et al. 1992a)
===References===
# Sonneveld P, Michiels JJ. Full dose chemotherapy in elderly patients with non-Hodgkin's lymphoma: a feasibility study using a mitoxantrone containing regimen. Br J Cancer. 1990 Jul;62(1):105-8. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
==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====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1 mg IV once on day 1
====Glucocorticoid therapy====
*Prednisolone (Millipred) 20 mg PO twice per day on days 1 to 5
21-day cycle for 6 cycles
===References===
# CLG NH 3003: Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 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====
*Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg/m2 (maximum dose of 2 mg) IV once per day on days 3, 10, 17, 24
*Methotrexate (MTX) 180 mg/m2 IV push once on day 12, then 120 mg/m2 IV over 4 hours (total dose: 300 mg/m2)
====Glucocorticoid therapy====
*Prednisone (Sterapred) 15 mg/m2 (maximum dose of 15 mg) PO four times per day on days 3 to 30, then tapered off over days 31 to 37
====CNS therapy, prophylaxis====
*Methotrexate (MTX) 6.25 mg/m2 IT once per day on days 5, 31, 34
37-day course
====Subsequent treatment====
*COMP maintenance
===References===
# Anderson JR, Wilson JF, Jenkin DT, Meadows AT, Kersey J, Chilcote RR, Coccia P, Exelby P, Kushner J, Siegel S, Hammond D. Childhood non-Hodgkin's lymphoma: the results of a randomized therapeutic trial comparing a 4-drug regimen (COMP) with a 10-drug regimen (LSA2-L2). N Engl J Med. 1983 Mar 10;308(10):559-65. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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-BCG2. CHOP-B	Might have lower 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====
*Cyclophosphamide (Cytoxan) 125 mg/m2 PO once per day on days 1 to 14
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once per day on days 1 & 8
*Bleomycin (Blenoxane) 4 mg/m2 IV once per day on days 1 & 8
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
28-day cycles
===References===
# Coltman CA Jr, Luce JK, McKelvey EM, Jones SE, Moon TE; SWOG. Chemotherapy of non-Hodgkin's lymphoma: 10 years' experience in the Southwest Oncology Group. Cancer Treat Rep. 1977 Sep;61(6):1067-78. EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
==CVP==
CVP: Cyclophosphamide, Vincristine, Prednisone
COP: Cyclophosphamide, Oncovin (Vincristine), Prednisone
VCP: Vincristine, Cyclophosphamide, Prednisone
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hoogstraten et al. 1969	Not reported 	Phase 3 (E-esc)	1. Cyclophosphamide	Higher CR rate
Hoogstraten et al. 1969	Not reported 	Phase 3 (E-esc)	2. CVP; lower-dose 	Not reported
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 15 mg/kg IV once on day 1
*Vincristine (Oncovin) 25 mcg/kg IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 1 mg/kg PO once per day on days 1 to 7
7-day cycle for 6 cycles
===Regimen variant #2===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Benjamin et al. 1976	1970-1973 	Randomized, fewer than 20 pts (E-de-esc)	MOPP 	Not reported
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1500 mg/m2 IV once on day 1
*Vincristine (Oncovin) 2 mg IV once per day on days 1 & 8
====Glucocorticoid therapy====
*Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 14
28-day cycles
===Regimen variant #3===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Bagley et al. 1972 	1967-1970 	Phase 2 	 	
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 shorter FFFP
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycles
===References===
# Hoogstraten B, Owens AH, Lenhard RE, Glidewell OJ, Leone LA, Olson KB, Harley JB, Townsend SR, Miller S, Spurr CL. Combination chemotherapy in lymphosarcoma and reticulum cell sarcoma. Blood. 1969 Feb;33(2):370-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 does not contain dosing details EuroPMC
==Cyclophosphamide monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Hoogstraten et al. 1969	Not reported 	Phase 3 (C)	CVP 	Lower CR rate
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 15 mg/kg IV once on day 1
7-day cycle for 4 to 6 cycles
===References===
# Hoogstraten B, Owens AH, Lenhard RE, Glidewell OJ, Leone LA, Olson KB, Harley JB, Townsend SR, Miller S, Spurr CL. Combination chemotherapy in lymphosarcoma and reticulum cell sarcoma. Blood. 1969 Feb;33(2):370-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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====
*Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
*Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2) 
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 5
*Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2 PO twice per day on days 1 to 5
====Supportive therapy====
*Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/μL past nadir
*PCP prophylaxis with ONE of the following:
**Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day 3 days per week 
**Atovaquone (Mepron) 1500 mg PO once per day 
**Pentamidine (Nebupent) 300 mg nebulized every 28 days
21-day cycle for 6 to 8 cycles; 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===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==DICEP==
DICEP: Dose Intensive Cyclophosphamide, Etoposide, Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence
Stewart et al. 2006	1998-2004 	Phase 2
====Preceding treatment====
*CHOP induction x 1
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 1750 mg/m2 IV over 2 hours once per day on days 1 to 3
*Etoposide (Vepesid) 350 mg/m2 IV over 2 hours once per day on days 1 to 3
*Cisplatin (Platinol) 35 mg/m2 IV over 2 hours once per day on days 1 to 3
====Supportive therapy====
*Mesna (Mesnex) 1750 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose: 5250 mg/m2)
*Filgrastim (Neupogen) by the following weight-based criteria:
**Less than 70 kg: 300 mcg SC once per day, started on day 14 and continued until stem cell collection completed
**70 to 100 kg: 480 mcg SC once per day, started on day 14 and continued until stem cell collection completed
**More than 70 kg: 600 mcg SC once per day, started on day 14 and continued until stem cell collection completed
One course
====Subsequent treatment====
*BEAM, then auto HSCT consolidation
===References===
# Stewart DA, Bahlis N, Valentine K, Balogh A, Savoie L, Morris DG, Jones A, Brown C, Russell JA. Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2006 Jun 15;107(12):4623-7. Epub 2006 Feb 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC 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	1980-01 to 1986-12 	Non-randomized
Infanti et al. 1996	1991-1996 	Non-randomized
Note: Enrollment dates for Amadori et al. 1985 are reported based on the 1991 update.
====Chemotherapy====
*Fluorouracil (5-FU) 15 mg/kg IV over 6 hours once on day 2 (hours 36 to 42)
*Methotrexate (MTX) 500 mg/m2 IV over 6 hours once on day 6 (hours 60 to 66)
*Cytarabine (Ara-C) 1000 mg/m2 IV over 6 hours once on day 3 (hours 42 to 48)
*Cyclophosphamide (Cytoxan) 800 mg/m2 IV bolus once on day 2 (hour 36)
*Doxorubicin (Adriamycin) 60 mg/m2 IV bolus once on day 3 (hour 48)
*Vincristine (Oncovin) 0.5 mg/m2 IV bolus twice per day on day 1 (hours 0 and 12)
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 14
====Supportive therapy====
*Leucovorin (Folinic acid) 20 mg/m2 IV bolus at hours 84, 96, 108, 120
21-day cycle for 6 cycles
===References===
# Amadori S, Guglielmi C, Anselmo AP, Cimino G, Ruco LP, Papa G, Biagini C, Mandelli F. Treatment of diffuse aggressive non-Hodgkin's lymphomas with an intensive multi-drug regimen including high-dose cytosine arabinoside (F-MACHOP). Semin Oncol. 1985 Jun;12(2 Suppl 3):218-22. EuroPMC 
## 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 EuroPMC
## 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. EuroPMC 
## 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==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 phase 3 RCT	 	
====Chemotherapy====
*Doxorubicin (Adriamycin) as follows:
**Cycles 1 to 6: 80 mg/m2 IV once on day 1
**Cycle 7: 70 mg/m2 IV once on day 1 (for a cumulative dose of 550 mg/m2)
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
14- to 21-day cycles
===References===
# McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 EuroPMC 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====
*Cyclophosphamide (Cytoxan) 250 mg/m2 IV once per day on days 1, 15, 29
*Doxorubicin (Adriamycin) 25 mg/m2 IV once per day on days 1, 15, 29
*Vincristine (Oncovin) 1.2 mg/m2 (maximum dose of 2 mg) IV once per day on days 8, 22, 36
*Bleomycin (Blenoxane) 10 units/m2 IV once per day on days 8, 22, 36
====Glucocorticoid therapy====
*Prednisone (Sterapred) as follows:
**Cycle 1: 50 mg PO once per day on days 1 to 42
**Cycle 2: 50 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41
====Supportive therapy====
*Cotrimoxazole
*Cimetidine (Tagamet)
*Ketoconazole (Nizoral)
42-day cycle for 2 cycles
===References===
# O'Reilly SE, Klimo P, Connors JM. Low-dose ACOP-B and VABE: weekly chemotherapy for elderly patients with advanced-stage diffuse large-cell lymphoma. J Clin Oncol. 1991 May;9(5):741-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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. CHOP2. 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 to not reported	Phase 3 (C) 	High-dose sequential therapy 	Shorter EFS
====Chemotherapy====
*Methotrexate (MTX) 400 mg/m2 IV once on day 8
*Doxorubicin (Adriamycin) 50 mg/m2 IV once per day on days 1 & 15
*Cyclophosphamide (Cytoxan) 350 mg/m2 IV once per day on days 1 & 15
*Vincristine (Oncovin) 1.4 mg/m2 IV once per day on days 8 & 22
*Bleomycin (Blenoxane) 10 units/m2 IV once on day 22
====Glucocorticoid therapy====
*Prednisone (Sterapred) as follows:
**Cycles 1 & 2: 75 mg PO once per day on days 1 to 28
**Cycle 3: 75 mg PO once per day on days 1 to 14, then tapered over last 15 days (schedule not reported)
====CNS therapy, prophylaxis====
*(for patients with bone marrow involvement):
*Methotrexate (MTX) 12 mg IT
====Supportive therapy====
*Trimethoprim-Sulfamethoxazole (Bactrim DS) 2 tablets (not specified if SS or DS) PO twice per day
28-day cycle for 3 cycles
===References===
# Klimo P, Connors JM. MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med. 1985 May;102(5):596-602. link to original article EuroPMC
## Update: Klimo P, Connors JM. Updated clinical experience with MACOP-B. Semin Hematol. 1987 Apr;24(2 Suppl 1):26-34. EuroPMC
# 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 EuroPMC
## 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 EuroPMC
# 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 EuroPMC
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
## 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. Epub 2011 Sep 21. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==m-BACOD==
m-BACOD: methotrexate (moderate dose), Bleomycin, Adriamycin (Doxorubicin), Cyclophosphamide, Oncovin (Vincristine), Dexamethasone
===Regimen variant #1===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Gordon et al. 1992 	1984-1988 	Phase 3 (E-esc)	CHOP 	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====
*Methotrexate (MTX) 200 mg/m2 IV once per day on days 8 & 15
*Bleomycin (Blenoxane) 4 units/m2 IV once on day 1
*Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 6 mg/m2 PO once per day on days 1 to 5
====Supportive therapy====
*Leucovorin (Folinic acid) 10 mg/m2 IV or PO once every 6 hours for 6 doses, starting 24 hours after each dose of methotrexate
21-day cycle for 8 cycles
===Regimen variant #2===
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
Fisher et al. 1993 (SWOG-8516/Intergroup 0067)	1986-1991 	Phase 3 (E-esc)	1. CHOP2. MACOP-B 3. ProMACE-CytaBOM	Did not meet endpoint of OS
====Chemotherapy====
*Methotrexate (MTX) 200 mg/m2 IV once per day on days 8 & 15
*Bleomycin (Blenoxane) 4 units/m2 IV once on day 1
*Doxorubicin (Adriamycin) 45 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 6 mg/m2 (no route specified) once per day on days 1 to 5
====Supportive therapy====
*Leucovorin (Folinic acid) 10 mg/m2 IV or PO every 6 hours on days 9 & 10, 16 & 17, starting 24 hours after each methotrexate
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===
# 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 EuroPMC
# 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. does not contain dosing details in abstract EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
## 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==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
Note: The abstract does not contain treatment details, and the original manuscript is not available online.
====Chemotherapy====
*Methotrexate (MTX)
*Bleomycin (Blenoxane)
*Mitoxantrone (Novantrone)
*Cyclophosphamide (Cytoxan)
*Vincristine (Oncovin)
====Glucocorticoid therapy====
*Dexamethasone (Decadron)
===References===
# Gherlinzoni F, Guglielmi C, Mazza P, Amadori S, Mandelli F, Tura S. Phase III comparative trial (m-BACOD v m-BNCOD) in the treatment of stage II to IV non-Hodgkin's lymphomas with intermediate- or high-grade histology. Semin Oncol. 1990 Dec;17(6 Suppl 10):3-8. does not contain dosing details in abstract EuroPMC
==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 was intended for elderly persons (65+ years of age). Although the original paper described this as an 8-week protocol, we express it here in cyclic fashion.
====Glucocorticoid therapy====
*Prednisone (Sterapred) 50 mg/day PO on days 1 to 10
====Chemotherapy====
*Doxorubicin (Adriamycin) as follows:
**Cycles 1 & 3: 40 mg/m2 IV once per day on days 1 & 8
*Vincristine (Oncovin) 1.2 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 300 mg/m2 IV once on day 1
*Etoposide (Vepesid) as follows:
**Cycle 2: 50 mg/m2 IV once on day 1, then 100 mg/m2 PO once per day on days 2 to 5
21-day cycle for 3 cycles
===References===
# O'Reilly SE, Connors JM, Howdle S, Hoskins P, Klasa R, Klimo P, Stuart DS. In search of an optimal regimen for elderly patients with advanced-stage diffuse large-cell lymphoma: results of a phase II study of P/DOCE chemotherapy. J Clin Oncol. 1993 Nov;11(11):2250-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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 longer 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====
*Prednisolone (Millipred) as follows:
**Cycles 1 to 4: 50 mg PO once per day
**Cycles 5 to 12: 50 mg PO once every other day
====Chemotherapy====
*Doxorubicin (Adriamycin) as follows:
**Cycles 1, 3, 5, 7, 9, 11: 35 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) as follows:
**Cycles 1, 3, 5, 7, 9, 11: 300 mg/m2 IV once on day 1
*Etoposide (Vepesid) as follows:
**Cycles 1, 3, 5, 7, 9, 11: 150 mg/m2 IV once on day 1
*Bleomycin (Blenoxane) as follows:
**Cycles 2, 4, 6, 8, 10, 12: 10 mg/m2 IV once on day 1
*Vincristine (Oncovin) as follows:
**Cycles 2, 4, 6, 8, 10, 12: 1.4 mg/m2 IV once on day 1
*Methotrexate (MTX) as follows:
**Cycles 2, 4, 6, 8, 10, 12: 100 mg/m2 IV once on day 1
7-day cycle for 12 cycles (see note)
===References===
# Linch DC, Smith P, Hancock BW, Hoskin PJ, Cunningham DC, Newland AC, Milligan D, Stevenson PA, Wood JK, Maclennan KA, Vaughan B, Vaughan G, Gregory WM; British National Lymphoma Investigation. A randomized British National Lymphoma Investigation trial of CHOP vs a weekly multi-agent regimen (PACEBOM) in patients with histologically aggressive non-Hodgkin's lymphoma. Ann Oncol. 2000;11 Suppl 1:87-90. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==PEN==
PEN: Prednisone, Etoposide, Novantrone (Mitoxantrone) 
===Regimen===
Study 	Dates of enrollment	Evidence
Goss et al. 1995	1991-1993 	Phase 2
====Glucocorticoid therapy====
*Prednisone (Sterapred) 50 mg PO once per day on days 1 to 14
====Chemotherapy====
*Etoposide (Vepesid) 50 mg PO once per day on days 1 to 14
*Mitoxantrone (Novantrone) 8 mg/m2 IV once on day 1
28-day cycles
===References===
# Goss P, Burkes R, Rudinskas L, King M, Chow W, Myers R, Davidson M, Poldre P, Crump M, Sutton D, Scott G. A phase II trial of prednisone, oral etoposide, and novantrone (PEN) as initial treatment of non-Hodgkin's lymphoma in elderly patients. Leuk Lymphoma. 1995 Jun;18(1-2):145-52. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==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 	Longer 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-CHOP1b. R-CHOEP1c. R-MACOP-B1d. R-PMitCEBO	Shorter EFS1EFS72: 55.8% vs 74.3%
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====
*Mitoxantrone (Novantrone) 7 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 300 mg/m2 IV once on day 1
*Etoposide (Vepesid) 150 mg/m2 IV once on day 1
*Bleomycin (Blenoxane) 10 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
7-day cycle for up to 16 cycles
===References===
# 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00005867
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00064116
## Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. Epub 2011 Sep 21. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==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 longer OS
Fisher et al. 1993 (SWOG-8516/Intergroup 0067)	1986-1991 	Phase 3 (E-esc) 	1. CHOP2. MACOP-B 3. m-BACOD	Did not meet endpoint of OS
====Glucocorticoid therapy====
*Prednisone (Prolix) 60 mg/m2 PO once per day on days 1 to 14
====Chemotherapy====
*Methotrexate (MTX) 120 mg/m2 IV once on day 8
*Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once on day 1
*Cytarabine (Ara-C) 300 mg/m2 IV once on day 8
*Bleomycin (Blenoxane) 5 units/m2 IV once on day 8
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 8
====Supportive therapy====
*Leucovorin (Folinic acid) 25 mg/m2 PO every 6 hours on day 9, starting 24 hours after methotrexate
*Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day throughout the course of treatment
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===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
## 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 EuroPMC
==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 shorter OS
Somers et al. 1994 (EORTC 20855)	1986-1991 	Phase 3 (E-switch-ic)	CHVmP-VB 	Higher ORR
Sertoli et al. 1994 	1987-1991 	Phase 3 (C) 	MACOP-B 	Did not meet endpoint of OS36
====Chemotherapy====
*Methotrexate (MTX) 500 mg/m2 IV once on day 15
*Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
*Etoposide (Vepesid) 120 mg/m2 IV once on day 1
*Mechlorethamine (Mustargen) 6 mg/m2 IV once on day 8
*Vincristine (Oncovin) 1.4 mg/m2 IV once on day 8
*Procarbazine (Matulane) 100 mg/m2 PO once per day on days 8 to 15
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 15
28-day cycle for 8 cycles
===References===
# Fisher RI, DeVita VT Jr, Hubbard SM, Longo DL, Wesley R, Chabner BA, Young RC. Diffuse aggressive lymphomas: increased survival after alternating flexible sequences of proMACE and MOPP chemotherapy. Ann Intern Med. 1983 Mar;98(3):304-9. link to original article EuroPMC
# 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 EuroPMC
# EORTC 20855: 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
==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====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine liposomal (Marqibo) 2 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
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====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine liposomal (Marqibo) 2 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle for 6 cycles
===References===
#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 dosing details in manuscript have been reviewed by our editors EuroPMC
==VABE==
VABE: Vincristine, Adriamycin (Doxorubicin), Bleomycin, Etoposide, Prednisone 
===Regimen===
Study 	Dates of enrollment	Evidence
O'Reilly et al. 1991	1983-1985 	Non-randomized
====Chemotherapy====
*Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg) IV once on day 8
*Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
*Bleomycin (Blenoxane) 5 units/m2 IV once on day 8
*Etoposide (Vepesid) 80 mg/m2 IV once on day 1, then 160 mg/m2 PO once on day 2
====Glucocorticoid therapy====
*Prednisone (Sterapred) as follows:
**Cycles 1 to 3: 50 mg PO once per day on days 1 to 14
**Cycles 4 to 6: 50 mg PO once every other day on days 1, 3, 5, 7, 9, 11, 13
====Supportive therapy====
*Hydrocortisone (Cortef) 100 mg IV once on day 8, given with bleomycin
*Cotrimoxazole
*Cimetidine (Tagamet)
*Ketoconazole (Nizoral)
14-day cycle for 6 cycles
===References===
# O'Reilly SE, Klimo P, Connors JM. Low-dose ACOP-B and VABE: weekly chemotherapy for elderly patients with advanced-stage diffuse large-cell lymphoma. J Clin Oncol. 1991 May;9(5):741-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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 	1985-10 to 1990-11 	Retrospective
Martelli et al. 1993	1988-1990 	Phase 2
====Chemotherapy====
*Etoposide (Vepesid) 100 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 350 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.2 mg/m2 (maximum dose of 2 mg) IV once on day 8
*Bleomycin (Blenoxane) 5 mg/m2 IV once on day 8
====Glucocorticoid therapy====
*Prednisone (Sterapred) 50 mg PO once per day on days 1 to 14
14-day cycle for 6 cycles
===References===
# Retrospective: Pichert G, Peters J, Stahel RA, Dommann C, Joss R, Gebbers JO, Kroner T, Sulser H, Honegger HP, Maurer R, Pampallona S. Chemotherapy with MACOP-B and VACOP-B for intermediate- and high-grade non-Hodgkin's lymphoma: clinical results and analysis of prognostic factors. Ann Oncol. 1992 Sep;3(8):645-9. link to original article EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==VCAP==
VCAP: Vindesine, Cyclophosphamide, Adriamycin (Doxorubicin), Prednisone
===Regimen===
Study 	Dates of enrollment	Evidence
Bernard et al. 2005	1984-1996 	Phase 2
====Chemotherapy====
*Vindesine (Eldisine) 4 mg/m2 IV once on day 1
*Cyclophosphamide (Cytoxan) 1500 mg/m2 IV once on day 2
*Doxorubicin (Adriamycin) 80 mg/m2 IV once on day 2
====Glucocorticoid therapy====
*Prednisone (Sterapred) 80 mg/m2 PO once per day on days 1 to 5
====CNS therapy, prophylaxis====
*Methotrexate (MTX) 15 mg IT once on day not specified (3 doses total)
21-day cycle for 3 cycles
===References===
# Bernard M, Cartron G, Rachieru P, LeMevel A, Branger B, Le Maignan C, Berthou C, Ghandour C, Delwail V, Milpied N, Cassasus P, Celigny PS, Guyotat D, Lamy T, Desablens B; GOELAMS. Long-term outcome of localized high-grade non-Hodgkin's lymphoma treated with high dose CHOP regimen and involved field radiotherapy: results of a GOELAMS study. Haematologica. 2005 Jun;90(6):802-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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====
*Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg) IV once per day on days 1, 8, 15
*Cyclophosphamide (Cytoxan) 350 mg/m2 IV once per day on days 1, 8, 15
*Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Prednisolone (Millipred) 40 mg/m2 PO once per day on days 1 to 3, 8 to 10, 15 to 17
21-day cycle for 2 cycles
===References===
# JCOG8101: Shimoyama M, Ota K, Kikuchi M, Yunoki K, Konda S, Takatsuki K, Ichimaru M, Ogawa M, Kimura I, Tominaga S, Tsugane S, Taguchi H, Minato K, Takenaka T, Tobinai K, Kurita S, Oyama A, Hisano S, Kozuru M, Matsumoto M, Nomura K, Takiguchi T, Sugai S, Yamaguchi K, Hattori T, Kinoshita K, Tajima K, Suemasu K. Chemotherapeutic results and prognostic factors of patients with advanced non-Hodgkin's lymphoma treated with VEPA or VEPA-M. J Clin Oncol. 1988 Jan;6(1):128-41. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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====
*Etoposide (Vepesid) 150 mg/m2 IV once on day 8
*Mitoxantrone (Novantrone) 10 mg/m2 IV once per day on days 1 & 15
*Cyclophosphamide (Cytoxan) 300 mg/m2 IV once per day on days 1 & 15
*Vincristine (Oncovin) 2 mg IV once per day on days 8 & 22
*Bleomycin (Blenoxane) 10 mg/m2 IV once on day 22
====Glucocorticoid therapy====
*Prednisone (Sterapred) as follows:
**Cycle 1: 40 mg IM once per day on days 1 to 28
**Cycle 2: 40 mg IM once per day on days 1 to 14, then tapered over the next 2 weeks
28-day cycle for 2 cycles
===References===
# Zinzani PL, Pavone E, Storti S, Moretti L, Fattori PP, Guardigni L, Falini B, Gobbi M, Gentilini P, Lauta VM, Bendandi M, Gherlinzoni F, Magagnoli M, Venturi S, Aitini E, Tabanelli M, Leone G, Liso V, Tura S. Randomized trial with or without granulocyte colony-stimulating factor as adjunct to induction VNCOP-B treatment of elderly high-grade non-Hodgkin's lymphoma. Blood. 1997 Jun 1;89(11):3974-9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
==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====
*Bortezomib (Velcade) 1.3 mg/m2 IV once per day on days 1 & 4
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
*Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
*Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
====Glucocorticoid therapy====
*Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Cornell 0309006313: "Standard" Acetaminophen (Tylenol) and Diphenhydramine (Benadryl) prior to rituximab
*C05013: Prophylaxis against VZV and PJP were recommended
21-day cycle for 6 cycles
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00151320
# C05013: Leonard JP, Kolibaba KS, Reeves JA, Tulpule A, Flinn IW, Kolevska T, Robles R, Flowers CR, Collins R, DiBella NJ, Papish SW, Venugopal P, Horodner A, Tabatabai A, Hajdenberg J, Park J, Neuwirth R, Mulligan G, Suryanarayan K, Esseltine DL, de Vos S. Randomized phase II study of R-CHOP with or without bortezomib in previously untreated patients with non-germinal center B-cell-like diffuse large B-cell lymphoma. J Clin Oncol. 2017 Nov 1;35(31):3538-3546. Epub 2017 Sep 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00931918
# 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 EuroPMC NCT01324596
=Consolidation after upfront therapy=
==Cyclophosphamide & TBI, then auto HSCT==
Cy/TBI: Cyclophosphamide & Total Body Irradiation
===Regimen===
Study 	Dates of enrollment	Evidence
Takvorian et al. 1987	1982-1987 	Non-randomized
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 60 mg/kg IV once per day on days -3 & -2
====Radiotherapy====
*Total body irradiation (TBI) 1200 cGy in fractions on days –6 to –4 (pulmonary dosage was limited to 800 cGy)
===References===
# Takvorian T, Canellos GP, Ritz J, Freedman AS, Anderson KC, Mauch P, Tarbell N, Coral F, Daley H, Yeap B, Schlossman SF, Nadler LM. Prolonged disease-free survival after autologous bone marrow transplantation in patients with non-Hodgkin's lymphoma with a poor prognosis. N Engl J Med. 1987 Jun 11;316(24):1499-505. link to original article EuroPMC
==Cytarabine & Methotrexate (CYM)==
CYM: CYtarabine, Methotrexate
===Regimen===
Study 	Dates of enrollment	Evidence
Milpied et al. 2004 (GOELAMS 072)	1994-1999 	Non-randomized part of phase 3 RCT
====Preceding treatment====
*Induction CEEP x 2
====Chemotherapy====
*Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 120 hours, started on day 37 (total dose: 500 mg/m2)
*Methotrexate (MTX) 3000 mg/m2 IV once on day 1
65-day course
====Subsequent treatment====
*BEAM with auto HSCT intensification
===References===
# GOELAMS 072: Milpied N, Deconinck E, Gaillard F, Delwail V, Foussard C, Berthou C, Gressin R, Lucas V, Colombat P, Harousseau JL; Groupe Ouest-Est des Leucémies et des Autres Maladies du Sang. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004 Mar 25;350(13):1287-95. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=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 shorter OS
Josting et al. 2005 	Not reported 	Phase 2 	 	
Note: Velasquez et al. 1988 reported 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====
*Dexamethasone (Decadron) 40 mg IV over 15 minutes once per day on days 1 to 4
====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====
*Metoclopramide (Reglan) 1 mg/kg (route and frequency not indicated)
*Diphenhydramine (Benadryl) 25 mg IV (frequency not indicated)
21- to 28-day cycle for 2 cycles (PARMA & Josting et al. 2005) or up to 10 cycles (see note)
====Subsequent treatment====
*PARMA, responders (PR/CR) after cycle 2: DHAP x 4 versus BEAC, then autologous HSCT consolidation
*Josting et al. 2005, responders (PR/CR) after cycle 2: HD-MTX with stem cell mobilization, then HDT, then autologous HSCT consolidation
===References===
# Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, Barlogie B. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
# 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 dosing details in abstract have been reviewed by our editors EuroPMC
==DHAP/VIM==
DHAP/VIM: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin) alternating with VP-16 (Etoposide), Ifosfamide, Methotrexate
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Vellenga et al. 2007 (HOVON-44)	2000-2005 	Phase 3 (C)	R-DHAP/R-VIM	Shorter PFS
Note: per the paper, "in case patients were non-responsive to DHAP but responsive to VIM, it was allowed to repeat the VIM regimen as the third cycle of reinduction chemotherapy." No statement was made as to whether Mesna was used in the VIM protocol.
====Glucocorticoid therapy, DHAP portion (cycles 1 & 3)====
*Dexamethasone (Decadron) 40 mg IV or PO once per day on days 1 to 4
====Chemotherapy, DHAP portion (cycles 1 & 3)====
*Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m2)
*Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours, started on day 1
====Chemotherapy, VIM portion (cycle 2)====
*Etoposide (Vepesid) 90 mg/m2 IV once per day on days 1, 3, 5
*Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 5
*Methotrexate (MTX) 30 mg/m2 IV once per day on days 1 & 5
28-day cycle for 3 cycles
====Subsequent treatment====
*HOVON-44, responders: Stem-cell mobilization, then BEAM with autologous hematopoietic stem cell transplant
===References===
#HOVON-44: Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15;111(2):537-43. Epub 2007 Oct 30. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00012051
==EPIC (carboplatin)==
EPIC: Etoposide, Prednisolone, Ifosfamide, Carboplatin
===Regimen===
Study 	Dates of enrollment	Evidence
Richardson et al. 1994	1991-1993 	Phase 2, fewer than 20 patients
====Chemotherapy====
*Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 4
*Ifosfamide (Ifex) 1000 mg/m2 IV once per day on days 1 to 5
*Carboplatin (Paraplatin) 60 mg/m2 IV once on day 10
====Glucocorticoid therapy====
*Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Mesna (Mesnex)
21-day cycles
===References===
# 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 EuroPMC
==EPIC (cisplatin)==
EPIC: Etoposide, Prednisolone, Ifosfamide, Cisplatin
===Regimen===
Study 	Dates of enrollment	Evidence
Hickish et al. 1993	1989-1991 	Phase 2
====Chemotherapy====
*Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 4
*Ifosfamide (Ifex) 1000 mg/m2 IV once per day on days 1 to 5
*Cisplatin (Platinol) 60 mg/m2 IV once on day 10
====Glucocorticoid therapy====
*Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
====Supportive therapy====
*Mesna (Mesnex)
21-day cycles
===References===
# Hickish T, Roldan A, Cunningham D, Mansi J, Ashley S, Nicolson V, Gore ME, Catovsky D, Smith IE. EPIC: an effective low toxicity regimen for relapsing lymphoma. Br J Cancer. 1993 Sep;68(3):599-604. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
==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====
*Cytarabine (Ara-C) 3000 mg/m2 IV every 12 hours on day 1 (2 doses)
*Mitoxantrone (Novantrone) 10 mg/m2 IV over 15 minutes once per day on days 2 & 3
21-day cycle for 2 cycles
===References===
# Ho AD, del Valle F, Rückle H, Schwammborn J, Schlimok G, Hiddemann W, Meusers P, Thiel E, Dörken B, Hunstein W. Mitoxantrone and high-dose cytarabine as salvage therapy for refractory non-Hodgkin's lymphoma. Cancer. 1989 Oct 1;64(7):1388-92. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==MINE==
MINE: Mesna, Ifosfamide, Novantrone (Mitoxantrone), Etoposide
VIM: Vepesid (Etoposide), Ifosfamide, Mitoxantrone
===Regimen variant #1===
Study 	Dates of enrollment	Evidence
Rodriguez et al. 1995	Not reported 	Phase 2
====Chemotherapy====
*Ifosfamide (Ifex) 1333 mg/m2 IV over 60 minutes once per day on days 1 to 3
*Mitoxantrone (Novantrone) 8 mg/m2 IV once on day 1
*Etoposide (Vepesid) 65 mg/m2 IV over 60 minutes once per day on days 1 to 3
====Supportive 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.
===Regimen variant #2===
Study 	Dates of enrollment	Evidence
Hopfinger et al. 1995	1986-1992 	Phase 2
====Chemotherapy====
*Ifosfamide (Ifex) 650 mg/m2 IV once per day on day 1 to 3
*Mitoxantrone (Novantrone) 3 mg/m2 IV once per day on day 1 to 3
*Etoposide (Vepesid) 65 mg/m2 IV once per day on day 1 to 3
====Supportive therapy====
*Mesna (Mesnex) 300 mg IV three times per day on days 1 to 3
21-day cycles
===References===
# Rodriguez MA, Cabanillas FC, Velasquez W, Hagemeister FB, McLaughlin P, Swan F, Romaguera JE. Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP. J Clin Oncol. 1995 Jul;13(7):1734-41. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==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====
*Dexamethasone (Decadron) 20 mg IV twice per day on days 1 to 4
====Chemotherapy====
*Etoposide (Vepesid) 75 mg/m2 IV once per day on days 1 to 4
*Ifosfamide (Ifex) 1200 mg/m2 IV once per day on days 1 to 4
*Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 4
====Supportive therapy====
*Mesna (Mesnex) 240 mg IV three times per day on days 1 to 4
21-day cycles
===References===
# Haim N, Rosenblatt E, Wollner M, Ben-Shahar M, Epelbaum R, Robinson E. Salvage therapy for non-Hodgkin's lymphoma with a combination of dexamethasone, etoposide, ifosfamide, and cisplatin. Cancer Chemother Pharmacol. 1992;30(3):243-4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=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	Not reported 	Phase 2
====Preceding treatment====
*MINE salvage induction
====Chemotherapy====
*Etoposide (Vepesid) 60 mg/m2 IV over 60 minutes once per day on days 1 to 4
*Cytarabine (Ara-C) 2000 mg/m2 IV over 2 hours once on day 5
*Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 100 mg/m2) 
====Glucocorticoid therapy====
*Methylprednisolone (Solumedrol) 500 mg IV as a short infusion once per day on days 1 to 4
21-day cycle for 3 cycles
===References===
# Rodriguez MA, Cabanillas FC, Velasquez W, Hagemeister FB, McLaughlin P, Swan F, Romaguera JE. Results of a salvage treatment program for relapsing lymphoma: MINE consolidated with ESHAP. J Clin Oncol. 1995 Jul;13(7):1734-41. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
=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====
*Cyclophosphamide (Cytoxan) 600 mg/m2 IV once per day on days 1 & 8
*Etoposide (Vepesid) 70 mg/m2 IV once per day on days 1 to 3
*Procarbazine (Matulane) 60 mg/m2 IV once per day on days 1 to 10
*Bleomycin (Blenoxane) 15 units/m2 (route not specified) once per day on days 1 & 15
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2 IV once per day on days 1 to 10
1-month cycles
====Dose and schedule modifications====
*Cyclophosphamide dose was increased by 50 mg/m2 with each cycle, if prior dose was tolerated
*Etoposide dose was increased by 15 mg/m2 with each cycle, if prior dose was tolerated
===References===
# Chao NJ, Rosenberg SA, Horning SJ. CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin's lymphoma. Blood. 1990 Oct 1;76(7):1293-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==DICE==
DICE: Dexamethasone, Ifosfamide, Cisplatin, Etoposide
===Regimen===
Study 	Dates of enrollment 	Evidence
Goss et al. 1991 	Not reported 	Phase 2
Coleman et al. 2001	Not reported in abstract	Phase 2
Note: The full manuscript for Coleman et al. 2001 was not available for review.
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 10 mg IV bolus four times per day on days 1 to 4
====Chemotherapy====
*Ifosfamide (Ifex) 1000 mg/m2 (maximum dose of 1750 mg) IV over 15 to 20 minutes once per day on days 1 to 4
*Cisplatin (Platinol) 25 mg/m2 IV over 60 minutes once per day on days 1 to 4
*Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 4
====Supportive therapy====
*Mesna (Mesnex)
21- to 28-day cycles
===References===
# Goss PE, Shepherd FA, Scott JG, Warner E, Baker MA, Sutton D, Farquharson HA, Buick S, Sutcliffe S. Dexamethasone/ifosfamide/cisplatin/etoposide (DICE) as therapy for patients with advanced refractory non-Hodgkin's lymphoma: preliminary report of a phase II study. Ann Oncol. 1991 Jan;2 Suppl 1:43-6. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
# 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. EuroPMC
==DICEP==
DICEP: Dose Intensive Cyclophosphamide, Etoposide, Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence
Neidhart et al. 1994	1987-1991 	Phase 2
Note: The cycle length was not reported in the abstract; the full manuscript is not available for online review.
====Chemotherapy====
*Cyclophosphamide (Cytoxan) 2500 mg/m2/day IV on days 1 & 2
*Etoposide (Vepesid) 500 mg/m2/day IV on days 1 to 3
*Cisplatin (Platinol) 50 mg/m2/day IV on days 1 to 3
One or more cycles
===References===
# Neidhart JA, Kubica R, Stidley C, Pfile J, Clark D, Rinehart J. Multiple cycles of dose-intensive cyclophosphamide, etoposide, and cisplatinum (DICEP) produce durable responses in refractory non-Hodgkin's lymphoma. Cancer Invest. 1994;12(1):1-11. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==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====
*Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
*Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2)
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 6
*Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2 PO on days 1 to 6
====Supportive therapy====
*Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC >5000/μL past nadir
*PCP prophylaxis with any one of the following:
**Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO twice per day 3 days per week 
**Atovaquone (Mepron) 1500 mg PO once per day 
**Pentamidine (Nebupent) 300 mg nebulized every 28 days
21-day cycle for 6 to 8 cycles
===References===
# Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD, Chabner BA. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug;11(8):1573-82. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
## 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 EuroPMC
==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 	Higher RR
Avilés et al. 2010 	Not reported 	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====
*Etoposide (Vepesid) 40 mg/m2 IV over 60 minutes once per day on days 1 to 4
*Cytarabine (Ara-C) 2000 mg/m2 IV over 2 hours once on day 5
*Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 100 mg/m2)
====Glucocorticoid therapy====
*Methylprednisolone (Solumedrol) 250 to 500 mg IV over 15 minutes once per day on days 1 to 5
====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===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 EuroPMC
==Etoposide, Ifosfamide, Methotrexate==
IMVP-16: Ifosfamide, Methotrexate, VP-16 (Etoposide)
===Regimen===
Study 	Dates of enrollment	Evidence
Cabanillas et al. 1982	Not reported 	Phase 2
====Chemotherapy====
*Ifosfamide (Ifex) 1000 mg/m2 IV over 60 minutes once per day on days 1 to 5
*Methotrexate (MTX) 30 mg/m2 (route not specified) once per day on days 3 & 10
*Etoposide (Vepesid) 100 mg/m2 IV over 2 hours once per day on days 1 to 3
21-day cycles
===References===
# Cabanillas F, Hagemeister FB, Bodey GP, Freireich EJ. IMVP-16: an effective regimen for patients with lymphoma who have relapsed after initial combination chemotherapy. Blood. 1982 Sep;60(3):693-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==GDP==
GDP: Gemcitabine, Dexamethasone, Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence
Crump et al. 2004	2001-2002 	Phase 2
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
*Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 40 mg IV or PO once per day on days 1 to 4
21-day cycle for up to 6 cycles
===References===
# Crump M, Baetz T, Couban S, Belch A, Marcellus D, Howson-Jan K, Imrie K, Myers R, Adams G, Ding K, Paul N, Shepherd L, Iglesias J, Meyer R; National Cancer Institute of Canada Clinical Trials Group. Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Cancer. 2004 Oct 15;101(8):1835-42. link to original article EuroPMC
==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 was intended to be followed by peripheral blood hematopoietic cell collection. Carboplatin AUC was calculated based on a 12-hour creatinine clearance.
====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
*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	Not reported 	Phase 2, fewer than 20 pts in this subgroup
Note: Third cycle was intended to be followed by peripheral blood hematopoietic cell collection
====Chemotherapy====
*Ifosfamide (Ifex) 1667 mg/m2 IV over 2 hours once per day on days 1 to 3, mixed with mesna
*Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV over 60 minutes once on day 1
*Etoposide (Vepesid) 100 mg/m2 IV over 30 minutes once per day on days 1 to 3
====Supportive therapy====
*Mesna (Mesnex) 1667 mg/m2 IV over 2 hours once per day on days 1 to 3, mixed with ifosfamide
*Filgrastim (Neupogen) 5 mcg/kg SC once per day, started on day 5
21-day cycle for 3 cycles
===References===
# Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lyons N, Agus DB, Goy A, Jurcic J, Noy A, O'Brien J, Portlock CS, Straus DS, Childs B, Frank R, Yahalom J, Filippa D, Louie D, Nimer SD, Zelenetz AD. Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3776-85. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC
==R-INO==
R-INO: Rituximab, INOtuzumab ozogamicin
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Fayad et al. 2013 (B1931004)	2006 to not reported	Phase 1/2 	 	
Dang et al. 2017 (B1931008) 	2011-2013 	Phase 3 (E-switch-ooc)	Investigator's choice of:1a. BR1b. Gemcitabine & Rituximab	Did not meet primary endpoint of OSMedian OS: 9.5 vs 9.5 mo(HR 1.10, 95% CI 0.80-1.40)
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
====Antibody-drug conjugate therapy====
*Inotuzumab ozogamicin (Besponsa) 1.8 mg/m2 IV once on day 2
28-day cycle for up to 8 cycles
===References===
# B1931004: Fayad L, Offner F, Smith MR, Verhoef G, Johnson P, Kaufman JL, Rohatiner A, Advani A, Foran J, Hess G, Coiffier B, Czuczman M, Giné E, Durrant S, Kneissl M, Luu KT, Hua SY, Boni J, Vandendries E, Dang NH. Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. J Clin Oncol. 2013 Feb 10;31(5):573-83. Epub 2013 Jan 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00299494
# B1931008: Dang NH, Ogura M, Castaigne S, Fayad LE, Jerkeman M, Radford J, Pezzutto A, Bondarenko I, Stewart DA, Shnaidman M, Sullivan S, Vandendries E, Tobinai K, Ramchandren R, Hamlin PA, Giné E, Ando K. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2018 Aug;182(4):583-586. Epub 2017 Jul 5. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT01232556
Category:Diffuse large B-cell lymphoma regimens
Category:Historical regimens
Category:Disease-specific pages
Category:Aggressive non-Hodgkin lymphomas
Category:B-cell lymphomas