Diffuse large B-cell lymphoma
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109 regimens on this page
165 variants on this page
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Untreated
ACVBP-R
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ACVBP-R: Adriamycin (Doxorubicin), Cyclophosphamide, Vindesine, Bleomycin, Prednisone, Rituximab
Synonyms: R-ACVBP
Structured Concept: none
Regimen
Study | Evidence | Comparator | Efficacy | Toxicity |
Récher et al. 2011 (LNH03-2B) | Phase III | R-CHOP | Improved OS | Increased toxicity |
Ketterer et al. 2013 (LNH03-1B) | Phase III | ACVBP |
Induction Regimen
- Doxorubicin (Adriamycin) 75 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV once on day 1
- Vindesine (Eldisine) 2 mg/m2 IV once per day on days 1 & 5
- Bleomycin (Blenoxane) 10 units IV once per day on days 1 & 5
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 5
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
CNS prophylaxis:
- Methotrexate (MTX) 15 mg intrathecal on day 1
Supportive medications:
- Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients ≥75 kg) SC once per day on days 6 to 13
14-day cycle x 4 cycles
Consolidation Regimen, part 1
- Methotrexate (MTX) 3000 mg/m2 IV once on day 1
Supportive medications:
14-day cycle x 2 cycles, beginning 4 weeks after completion of induction, then
Consolidation Regimen, part 2
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Etoposide (Vepesid) 300 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 1500 mg/m2 IV once on day 1
14-day cycle x 4 cycles, beginning 2 weeks after completion of MTX, then
Consolidation Regimen, part 3
- Cytarabine (Cytosar) 100 mg/m2 SC once per day on days 1 to 4
14-day cycle x 2 cycles, beginning 2 weeks after completion of REI
References
- Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. link to original article contains verified protocol PubMed
- Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. link to original article PubMed
CHOP
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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Synonyms: CHOP-21, ACOP, CAVP, COPA, VACP, VCAP
Structured Concept: C9549 (NCI-T), C0055598 (NCI-MT/UMLS)
Regimen #1
Study | Evidence | Comparator | |
Elias et al. 1978 | Non-randomized | ||
Fisher et al. 1993 (SWOG-8516/Intergroup 0067) | Phase III | MACOP-B; m-BACOD; ProMACE-CytaBOM | |
Miller et al. 1998 | Phase III | CHOP x 3 -> RT |
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV bolus over 1 to 2 minutes once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV bolus over 1 to 2 minutes once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle x 8 cycles
Regimen #2
Study | Evidence | Comparator |
Pfreundschuh et al. 2004 (NHL-B1) | Phase III | CHOEP-14 CHOEP-21 CHOP-14 |
Verdonck et al. 2007 | Phase III | I-CHOP |
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications (only listed in Pfreundschuh et al. 2004):
- At the discretion of ordering physician: Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13
21-day cycle x 6 cycles
Regimen #3, CHOP x3 -> XRT
Study | Evidence | Comparator |
Miller et al. 1998 | Phase III | CHOP x 8 |
Reyes et al. 2005 | Phase III | ACVBP |
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV bolus over 1 to 2 minutes once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV bolus over 1 to 2 minutes once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle x 3 cycles, then followed by radiation therapy
Radiation therapy, starting 3 weeks after cycle 3 of CHOP:
- Involved field radiation therapy, 180-200 cGy fractions, total dose of 4000-5500 cGy. Total dose was often influenced by whether patients had clinical evidence of residual disease after 4000 cGy.
Regimen #4
Study | Evidence | Comparator | |
Coiffier et al. 2002 (LNH-98.5) | Phase III | R-CHOP | |
Tilly et al. 2003 | Phase III | ACVBP |
- 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 per cycle) IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
Supportive medications:
- Filgrastim (Neupogen) used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
21-day cycle x 8 cycles
Regimen #5
Study | Evidence | Comparator | Efficacy |
Habermann et al. 2006 (CALGB 9793) | Phase III | R-CHOP | Might have inferior FFS |
- 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 per cycle: 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
Supportive medications:
- Filgrastim (Neupogen) "recommended according to guidelines"
21-day cycle x 6 to 8 cycles
Patients with CR/PR proceeded to receive maintenance rituximab versus observation.
Regimen #6
Study | Evidence | Comparator |
Pfreundschuh et al. 2004 (NHL-B2) | Phase III | CHOEP-14 CHOEP-21 CHOP-14 |
Pre-phase treatment
Recommended "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle."
- Vincristine (Oncovin) 1 mg IV once (day not specified)
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 7
7-day course, then proceed to main regimen
Main CHOP regimen
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications
- Filgrastim (Neupogen) "at the treating physician's discretion"
21-day cycle x 6 cycles
Radiation therapy for initial bulky disease
"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter =7.5 cm) or extranodal involvement"
- Radiation therapy, 36 Gy to areas of initial bulky disease
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. PubMed
- Elias L, Portlock CS, Rosenberg SA. Combination chemotherapy of diffuse histiocytic lymphoma with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). Cancer. 1978 Oct;42(4):1705-10. link to original article contains verified protocol PubMed
- Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, et al. Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. Ann Oncol. 1992 Mar;3(3):205-9. link to original article PubMed
- Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. link to original article PubMed
- Update: Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate- or high-grade non-Hodgkin's lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study. Ann Oncol. 1994;5 Suppl 2:91-5. PubMed
- Update: Bernstein SH, Unger JM, Leblanc M, Friedberg J, Miller TP, Fisher RI. Natural history of CNS relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 8516 -- the Southwest Oncology Group. J Clin Oncol. 2009 Jan 1;27(1):114-9. Epub 2008 Dec 1. link to original article PubMed
- Tondini C, Zanini M, Lombardi F, Bengala C, Rocca A, Giardini R, Buzzoni R, Valagussa P, Bonadonna G. Combined modality treatment with primary CHOP chemotherapy followed by locoregional irradiation in stage I or II histologically aggressive non-Hodgkin's lymphomas. J Clin Oncol. 1993 Apr;11(4):720-5. link to original article PubMed
- Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2;339(1):21-6. link to original article contains verified protocol PubMed
- Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. link to original article contains verified protocol PubMed
- Update: Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. link to original article contains protocol PubMed
- Update: Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. link to original article contains verified protocol PubMed
- Update: Mounier N, Heutte N, Thieblemont C, Briere J, Gaulard P, Feugier P, Ghesquieres H, Van Den Neste E, Robu D, Tilly H, Bouabdallah R, Safar V, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte (GELA). Ten-year relative survival and causes of death in elderly patients treated with R-CHOP or CHOP in the GELA LNH-985 trial. Clin Lymphoma Myeloma Leuk. 2012 Jun;12(3):151-4. Epub 2012 Feb 1. link to original article PubMed
- Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. Epub 2003 Aug 14. link to original article contains verified protocol PubMed
- Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains verified protocol PubMed
- Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. link to original article contains verified protocol PubMed
- Reyes F, Lepage E, Ganem G, Molina TJ, Brice P, Coiffier B, Morel P, Ferme C, Bosly A, Lederlin P, Laurent G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte (GELA). ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005 Mar 24;352(12):1197-205. link to original article PubMed
- Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains verified protocol PubMed
- Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial (MInT) Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. link to original article contains protocol PubMed
- Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. link to original article contains verified protocol PubMed
- Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thiéblemont C, Fermé C, Quesnel B, Martin C, Gisselbrecht C, Tilly H, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2007 Mar 1;25(7):787-92. Epub 2007 Jan 16. link to original article contains protocol PubMed
- Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. link to original article contains verified protocol PubMed
CHOP Intensified
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CHOP-DI: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Dose Intense
I-CHOP: Intensified Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Synonyms: CHOP-14, CHOP-DI, I-CHOP
Structured Concept: none
Regimen #1
Study | Evidence |
Blayney et al. 2003 (CHOP-DI, SWOG 9349) | Phase II |
- Cyclophosphamide (Cytoxan) 1600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 65 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 11, or until ANC is greater than 10,000
14-day cycles x up to 6 cycles
Regimen #2
Study | Evidence | Comparator |
Verdonck et al. 2007 | Phase III | CHOP |
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 70 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 2 to 11
14-day cycles x 6 cycles
Regimen #3
Study | Evidence | Comparator | |
Pfreundschuh et al. 2004 (NHL-B1) | Phase III | CHOEP-14 | |
Pfreundschuh et al. 2004 (NHL-B1) | Phase III | CHOEP-21 | |
Pfreundschuh et al. 2004 (NHL-B1) | Phase III | CHOP | |
Pfreundschuh et al. 2008 (RICOVER-60) | Phase III | R-CHOP-14 |
Pre-phase treatment
Recommended in Pfreundschuh et al. 2004, but mandatory in Pfreundschuh et al. 2008 "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle." A difference was that the prednisone in Pfreundschuh et al. 2004 could be given for 5 to 7 days.
- Vincristine (Oncovin) 1 mg IV once (day not specified)
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 7
7-day course, then proceed to main CHOP-14 regimen
Main CHOP-14 regimen
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications (per Pfreundschuh et al. 2004):
- Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC once per day on days 4 to 13
14-day cycles x 6 cycles; some patients in Pfreundschuh et al. 2008 received 14-day cycles x 8 cycles
Radiation therapy for initial bulky disease
"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter =7.5 cm) or extranodal involvement"
- Radiation therapy, 36 Gy to areas of initial bulky disease
References
- Blayney DW, LeBlanc ML, Grogan T, Gaynor ER, Chapman RA, Spiridonidis CH, Taylor SA, Bearman SI, Miller TP, Fisher RI; Southwest Oncology Group. Dose-intense chemotherapy every 2 weeks with dose-intense cyclophosphamide, doxorubicin, vincristine, and prednisone may improve survival in intermediate- and high-grade lymphoma: a phase II study of the Southwest Oncology Group (SWOG 9349). J Clin Oncol. 2003 Jul 1;21(13):2466-73. link to original article contains verified protocol PubMed
- Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains verified protocol PubMed
- Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. link to original article contains verified protocol PubMed
- Verdonck LF, Notenboom A, de Jong DD, MacKenzie MA, Verhoef GE, Kramer MH, Ossenkoppele GJ, Doorduijn JK, Sonneveld P, van Imhoff GW. Intensified 12-week CHOP (I-CHOP) plus G-CSF compared with standard 24-week CHOP (CHOP-21) for patients with intermediate-risk aggressive non-Hodgkin lymphoma: a phase 3 trial of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON). Blood. 2007 Apr 1;109(7):2759-66. link to original article contains verified protocol PubMed
- Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. link to original article contains verified protocol PubMed
CHOP Modified
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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence | Comparator | Efficacy |
Bessell et al. 2003 | Phase III | MCOP | Seems not superior |
This regimen is designed for elderly patients and is of lower intensity than standard CHOP.
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg IV once on day 1
- Prednisolone (Millipred) 20 mg PO BID on days 1 to 5
21-day cycles x 6 cycles
References
- Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. link to original article contains verified protocol PubMed
CHOP -> IFRT -> Ibritumomab tiuxetan
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CHOP: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence |
Persky et al. 2014 (SWOG S0313) | Phase II |
This regimen is intended for limited-stage aggressive B-cell NHL; the majority of patients studied had DLBCL.
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 per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle x 3 cycles, followed by:
Radiation therapy
Involved-field radiation therapy to begin 3 weeks after last cycle of CHOP, see paper for details.
Complete course followed in 3 to 6 weeks by:
Consolidation radioimmunotherapy
- Rituximab (Rituxan) 250 mg/m2 IV once on day 1, then another single dose on day 7, 8 or 9
- Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (maximum dose of 32 mCi) IV once, given within four hours of second dose of Rituximab (Rituxan)
References
- Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. Epub 2014 Nov 13. link to original article contains verified protocol PubMed
CNOP, MCOP
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CNOP: Cyclophosphamide, Novantrone (Mitoxantrone), Oncovin (Vincristine), Prednisone
MCOP: Mitoxantrone, Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence | Comparator | Efficacy |
Sonneveld et al. 1990 | Phase II | ||
Pavlovsky et al. 1992 | Phase III | CHOP | |
Bessell et al. 2003 | Phase III | Modified CHOP | Seems not superior |
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once on day 1
- Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg IV once on day 1
- Prednisolone (Millipred) 20 mg PO BID on days 1 to 5
21-day cycles x 6 cycles
References
- Sonneveld P, Michiels JJ. Full dose chemotherapy in elderly patients with non-Hodgkin's lymphoma: a feasibility study using a mitoxantrone containing regimen. Br J Cancer. 1990 Jul;62(1):105-8. link to original article PubMed
- Pavlovsky S, Santarelli MT, Erazo A, Diaz Maqueo JC, Somoza N, Lluesma Goñalons M, Cervantes G, Garcia Vela EL, Corrado C, Magnasco H, et al. Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. Ann Oncol. 1992 Mar;3(3):205-9. link to original article PubMed
- Bessell EM, Burton A, Haynes AP, Glaholm J, Child JA, Cullen MH, Davies JM, Smith GM, Ellis IO, Jack A, Jones EL; Central Lymphoma Group UK. A randomised multicentre trial of modified CHOP versus MCOP in patients aged 65 years and over with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003 Feb;14(2):258-67. link to original article contains verified protocol PubMed
DA-R-EPOCH
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DA-R-EPOCH: Dose Adjusted Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
Synonyms: DA-EPOCH-R, EPOCH-R, REPOCH
Structured Concept: C63461 (NCI-T), C1882521 (NCI-MT/UMLS)
Regimen
Study | Evidence | ||
García-Suárez et al. 2007 | Phase II | ||
Wilson et al. 2008 | Phase II | ||
Wilson et al. 2012 | Phase II | ||
Purroy et al. 2014 | Phase II |
- Rituximab (Rituxan) 375 mg/m2 IV once per cycle or day 1 before the start of EPOCH (depending on reference)
- Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion on days 1 to 4 (total dose of 200 mg/m2)
- Prednisone (Sterapred) 60 mg/m2 PO BID on days 1 to 5
- Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion on days 1 to 4 (total dose of 1.6 mg/m2)
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once over 15 minutes on day 5
- Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion on days 1 to 4 (total dose of 40 mg/m2)
Supportive medications:
- Growth factor support with one of the following:
- Filgrastim (Neupogen) 5 mcg/kg SQ once per day, starting on day 6 and continuing until ANC >5,000/uL past nadir
- Pegfilgrastim (Neulasta) 6 mg SC once on day 6 (option per Purroy et al. 2014)
- PCP prophylaxis with any one of the following:
- Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO BID 3 days per week
- Alternative used only in García-Suárez et al. 2007: cotrimoxazole 480 mg PO BID 3 days per week
- Atovaquone (Mepron) 1500 mg PO once per day
- Pentamidine (Nebupent) 300 mg nebulized every 28 days
- Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO BID 3 days per week
- Only in García-Suárez et al. 2007: Darbepoetin alfa (Aranesp) 2.25 ug/kg SC when hemoglobin concentration was ≤100 g/l.
21-day cycle x 6 to 8 cycles
Dose-adjustments for EPOCH protocol:
- Start cycle 1 as described above.
- Obtain CBCs twice per week for nadir measurements.
- If nadir ANC >500, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
- If nadir ANC <500 on 1 or 2 measurements, use same doses as last cycle.
- If nadir ANC <500 on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
- And/or if nadir platelet count <25 on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
- Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide. The lowest etoposide and doxorubicin would be dosed at is the original cycle 1 dose.
- Can start new cycle every 21 days if ANC >1,000 and platelets >100. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.
References
- García-Suárez J, Bañas H, Arribas I, De Miguel D, Pascual T, Burgaleta C. Dose-adjusted EPOCH plus rituximab is an effective regimen in patients with poor-prognostic untreated diffuse large B-cell lymphoma: results from a prospective observational study. Br J Haematol. 2007 Jan;136(2):276-85. link to original article contains verified protocol PubMed
- Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. link to original article PubMed
- Wilson WH, Jung SH, Porcu P, Hurd D, Johnson J, Martin SE, Czuczman M, Lai R, Said J, Chadburn A, Jones D, Dunleavy K, Canellos G, Zelenetz AD, Cheson BD, Hsi ED; Cancer Leukemia Group B. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Haematologica. 2012 May;97(5):758-65. Epub 2011 Dec 1. link to original article PubMed
- Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, García-Marco JA, Castellví J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma. A phase II study conducted by the Spanish PETHEMA Group. Br J Haematol. 2015 Apr;169(2):188-98. Epub 2014 Dec 18. link to original article contains protocol PubMed
- Retrospective: Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. link to original article PubMed
Helicobacter pylori eradication therapy
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Regimen
This regimen is intended for the treatment of gastric DLBCL only; H. pylori eradication would not be an appropriate treatment for systemic DLBCL.
Before 1996:
- Amoxicillin 500mg PO q6h x 28 days
- Metronidazole (Flagyl) 250mg PO q6h x 28 days
- EITHER bismuth subcitrate 120mg PO q6h x 28 days
- OR Omeprazole (Prilosec) 20mg PO BID x 28 days
After 1996:
- Amoxicillin 500mg PO q6h x 14 days
- Clarithromycin (Biaxin) 500mg PO BID x 14 days
- Omeprazole (Prilosec) 20mg PO BID x 14 days
References
- Kuo SH, Yeh KH, Wu MS, Lin CW, Hsu PN, Wang HP, Chen LT, Cheng AL. Helicobacter pylori eradication therapy is effective in the treatment of early-stage H pylori-positive gastric diffuse large B-cell lymphomas. Blood. 2012 May 24;119(21):4838-44; quiz 5057. Epub 2012 Mar 7. link to original article PubMed
R-CDOP, DRCOP
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R-CDOP: Rituximab, Cyclophosphamide, Doxil (Pegylated liposomal doxorubicin), Oncovin (Vincristine), Prednisone
DRCOP: Doxil (Pegylated liposomal doxorubicin), Rituximab, Cyclophosphamide, Oncovin (Vincristine), Prednisone
Regimen #1
Study | Evidence |
Oki et al. 2014 | Phase II |
- Doxorubicin liposomal (Doxil) 40 mg/m2 (maximum dose of 90 mg) IV over 60 minutes once on day 1
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg per IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
Supportive medications:
- Filgrastim (Neupogen) 5 μg/kg SC once per day from day 2 until ANC > 3000/μl
OR
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2
Dose modifications:
- Dose reduction level 1 (see paper for triggers):
- Doxorubicin liposomal (Doxil) reduced to 35 mg/m2
- Cyclophosphamide (Cytoxan) reduced to 600 mg/m2
- Dose reduction level 2 (see paper for triggers):
- Doxorubicin liposomal (Doxil) reduced to 30 mg/m2
- Cyclophosphamide (Cytoxan) reduced to 450 mg/m2
21-day cycle x 6 to 8 cycles
Regimen #2
Study | Evidence |
Zaja et al. 2006 | Phase II |
Only the dose of liposomal doxorubicin and number of cycles used was specified in the abstract. The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin liposomal (Doxil) 30 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle x 6 cycles
References
- Zaja F, Tomadini V, Zaccaria A, Lenoci M, Battista M, Molinari AL, Fabbri A, Battista R, Cabras MG, Gallamini A, Fanin R. CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2006 Oct;47(10):2174-80. link to original article PubMed
- Oki Y, Ewer MS, Lenihan DJ, Fisch MJ, Hagemeister FB, Fanale M, Romaguera J, Pro B, Fowler N, Younes A, Astrow AB, Huang X, Kwak LW, Samaniego F, McLaughlin P, Neelapu SS, Wang M, Fayad LE, Durand JB, Rodriguez MA. Pegylated liposomal doxorubicin replacing conventional doxorubicin in standard R-CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma: an open label, single arm, phase II trial. Clin Lymphoma Myeloma Leuk. 2015 Mar;15(3):152-8. Epub 2014 Sep 28. link to original article contains verified protocol PubMed
R-CEOP90 (Epirubicin)
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R-CEOP90: Rituximab, Cyclophosphamide, Epirubicin (90 mg/m2 dosing), Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence |
Cai et al. 2014 | Phase II |
This regimen is intended to reduce cardiotoxicity and was not just for patients with contraindicated doxorubicin. Note that the cycle length is not explicitly defined in the paper but was reported as a median of 21 days (range 21 to 33 days).
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 2
- Epirubicin (Ellence) 90 mg/m2 IV once on day 2
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 2
- Prednisolone (Millipred) 100 mg/day on days 2 to 6
21-day cycle x 4 cycles followed by involved field radiotherapy (30-45 Gy) of bulky disease and extranodal and residual masses for patients with stage IA or IIA disease; 6 cycles for all others
References
- Cai QC, Gao Y, Wang XX, Cai QQ, Lin ZX, Bai B, Guo Y, Huang HQ. Long-term results of the R-CEOP90 in the treatment of young patients with chemotherapy-naïve diffuse large B cell lymphoma: a phase II study. Leuk Lymphoma. 2014 Oct;55(10):2387-8. link to original article contains verified protocol PubMed
R-CEOP (Etoposide)
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R-CEOP: Rituximab, Cyclophosphamide, Etoposide, Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence |
Moccia et al. 2009 | Retrospective |
This regimen is intended for patients with a contraindication to anthracyclines. Only the dose of etoposide and number of cycles used was specified in the abstract. The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Etoposide (Vepesid) 50 mg/m2 IV once on day 1; 100 mg/m2 PO once per day on days 2 & 3
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
- Alternate dosing used in the R-CHOP regimens described in Coiffier et al. 2002 & 2010; Feugier et al. 2005; Mounier et al. 2012 - LNH-98.5 is Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
21-day cycles x 3 to 4 cycles +/- radiation therapy for patients with limited stage disease; 6 cycles for patients with advanced stage disease
References
- Retrospective: Abstract: Moccia, Alden A., Schaff, Kimberly, Hoskins, Paul, Klasa, Richard, Savage, Kerry J., Shenkier, Tamara, Gascoyne, Randy D., Connors, Joseph M., Sehn, Laurie H. R-CHOP with Etoposide Substituted for Doxorubicin (R-CEOP): Excellent Outcome in Diffuse Large B Cell Lymphoma for Patients with a Contraindication to Anthracyclines. ASH Annual Meeting Abstracts 2009 114: 408 link to abstract
R-CHMP
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R-CHMP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Marqibo (Vincristine liposomal), Prednisone
Regimen
Study | Evidence |
Hagemeister et al. 2013 | Phase II |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin liposomal (Doxil) 50 mg/m2 IV once on day 1
- Vincristine liposomal (Marqibo) 2 mg/m2 IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycles x 6 cycles; stage I patients with no LN > 5 cm received 3 cycles followed by local XRT
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 contains verified protocol PubMed
R-CHOEP-14
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R-CHOEP-14: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Etoposide, Prednisone, 14-day cycles
Regimen #1
Study | Evidence | Comparator | Efficacy | Toxicity |
Schmitz et al. 2012 (DSHNHL 2002-1) | Phase III | R-MegaCHOEP | Seems not superior | Decreased toxicity |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 0 (cycles 1 to 4, 6, and 8)
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
14-day cycle x 8 cycles
Radiotherapy
- 36 Gy in daily fractions "mandatory" for patients with bulky disease (any mass > 7.5cm in diameter, or extranodal involvement)
Regimen #2, with CNS prophylaxis
Study | Evidence |
Holte et al. 2013 | Phase II |
R-CHOEP
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- 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
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC once per day from day 4 or Pegfilgrastim (Neulasta) 6 mg SC once on day 4
14-day cycle x 8 cycles, followed by:
CNS Prophylaxis
Note that IT treatment was not part of prophylaxis, except that Methotrexate (MTX) 15 mg IT was allowed at time of diagnostic LP.
- Cytarabine (Cytosar) 3000 mg/m2 IV BID for 2 days (4 doses)
- Dose reduced to 2000 mg/m2 for patients aged 60-65 years
Followed 3 weeks later by:
- Methotrexate (MTX) 3000 mg/m2 IV continuous infusion over 24 hours
Supportive medications:
- Folinic acid (Leucovorin) (dose/frequency not specified) starting at 36 hours
One course
Radiotherapy
- "Given at the discretion of the individual centers (36–45 Gy). Indications for giving radiotherapy after the completion of chemotherapy included bulky disease (≥10 cm) at diagnosis, localized PET-positive residual lesions, and residual disease, not eligible for biopsy at a localized site, and potentially curable by radiotherapy."
References
- Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, Viardot A, Bentz M, Peter N, Ehninger G, Doelken G, Ruebe C, Truemper L, Rosenwald A, Pfreundschuh M, Loeffler M, Glass B; for the German High-Grade Lymphoma Study Group (DSHNHL). Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012 Dec;13(12):1250-1259. Epub 2012 Nov 16. link to original article PubMed
- Holte H, Leppä S, Björkholm M, Fluge O, Jyrkkiö S, Delabie J, Sundström C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fosså A, Ostenstad B, Löfvenberg E, Nordström M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. Epub 2012 Dec 17. link to original article contains verified protocol PubMed
R-CHOP
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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Synonyms: R-CHOP-21, CHOP-R
Structured Concept: C9760 (NCI-T), C0393023 (NCI-MT/UMLS)
Regimen #1
Study | Evidence | Comparator |
Offner et al. 2015 | Randomized Phase II | VR-CAP |
This regimen was used for non-germinal center B-cell (non-GCB) DLBCL.
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- 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 per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycle x 6 cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
Coiffier et al. 2002 (LNH-98.5) | Phase III | CHOP | |
Delarue et al. 2013 (LNH03-6B) | Phase III | R-CHOP14 | Seems not superior |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- 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 per cycle) IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
CNS prophylaxis: As described in Delarue et al. 2013 (LNH03-6B):
- Methotrexate (MTX) 15 mg IT once every 21 days x 4 total doses
Supportive medications:
- Filgrastim (Neupogen) used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
21-day cycle x 8 cycles
Regimen #3
Study | Evidence | Comparator | Efficacy | Toxicity |
Pfreundschuh et al. 2006 (MInT) | Phase III | CHOP | Superior EFS | Similar toxicity |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
- Radiation therapy: 30 to 40 Gy given to sites of primary bulky disease; 30 to 40 Gy to primary extranodal disease at physician discretion
Supportive medications:
- Filgrastim (Neupogen) or Lenograstim (Granocyte) used at physician discretion for neutropenia
21-day cycle x 6 cycles
Regimen #4
Study | Evidence | Comparator | Efficacy |
Habermann et al. 2006 (CALGB 9793) | Phase III | CHOP | Might have superior FFS |
- Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m2 IV once per day on days -7 & -3
- Cycle 2 onwards: 375 mg/m2 IV once on day -2
- 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 per cycle: 2 mg) IV once on day 1
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
Supportive medications:
- Filgrastim (Neupogen) "recommended according to guidelines"
21-day cycle x 6 to 8 cycles
This trial also included a randomization to maintenance rituximab versus observation for responders; however an advantage was only seen in the group receiving CHOP upfront, which is no longer standard of care.
Regimen #5
Study | Evidence | Comparator | Efficacy |
Merli et al. 2012 (ANZINTER3) | Phase III | R-miniCEOP | Equivalent RR |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- 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 per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg PO/IV once per day on days 1 to 5
Supportive medications:
- Prophylactic G-CSF used for persisting grade 4 neutropenia or febrile neutropenia.
- Cotrimoxazole (dose/schedule not specified) prophylaxis.
- Erythropoietin use was allowed for hemoglobin <11 g/dL.
21-day cycle x 6 cycles
Radiation therapy
"At the end of chemotherapy, radiotherapy (RT) was scheduled for sites of previous bulky disease or partially responding sites."
Regimen #6
Study | Evidence | Comparator | Efficacy |
Cunningham et al. 2013 | Phase III | R-CHOP-14 | Not superior |
Note: Cunningham et al. 2013 said that it based its regimen on Coiffier et al. 2002, but notably it uses prednisolone instead of prednisone.
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- 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 per cycle) IV once on day 1
- Prednisolone (Millipred) 40 mg/m2 PO once per day on days 1 to 5
CNS prophylaxis: Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
- Methotrexate (MTX) 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
Supportive medications:
- Lenograstim (Granocyte) (dose/route not specified) given on days 4 to 12 at physician discretion
- Allopurinol (Zyloprim) 300 mg PO once per day during cycle 1
- Co-trimoxazole 480 mg (route not specified) BID on 3 days per week, taken throughout therapy, ending 2 weeks after chemotherapy is completed
21-day cycle x 8 cycles
Regimen #7
Study | Evidence |
Persky et al. 2008 (SWOG S0014) | Phase II |
Chemotherapy
- Rituximab (Rituxan) 375 mg/m2 IV once on days -7, 1, 22, 43 (4 doses total)
- 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 per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
21-day cycle x 3 cycles, followed by:
Radiation therapy
Involved-field radiation therapy to begin 3 weeks after last cycle of R-CHOP, see paper for details.
Regimen #8
Study | Evidence |
Vitolo et al. 2011 (IELSG-10) | Phase II |
This regimen is for primary testicular lymphoma. All patients had a diagnostic orchiectomy prior to starting chemotherapy.
Chemotherapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 0 or 1
- 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 per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
CNS Prophylaxis:
- Methotrexate (MTX) 12 mg IT once per week x 4 total doses
21-day cycle x 6 cycles (up to 8 cycles for stage II patients), followed by:
Radiation therapy
25 to 30 Gy to the contralateral testis. For patients with stage II disease, involved-field radiation therapy was added, see paper for details.
References
- Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. link to original article contains verified protocol PubMed
- Update: Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. link to original article contains protocol PubMed
- Update: Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. link to original article contains verified protocol PubMed content property of HemOnc.org
- Update: Mounier N, Heutte N, Thieblemont C, Briere J, Gaulard P, Feugier P, Ghesquieres H, Van Den Neste E, Robu D, Tilly H, Bouabdallah R, Safar V, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte (GELA). Ten-year relative survival and causes of death in elderly patients treated with R-CHOP or CHOP in the GELA LNH-985 trial. Clin Lymphoma Myeloma Leuk. 2012 Jun;12(3):151-4. Epub 2012 Feb 1. link to original article PubMed
- Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains verified protocol PubMed
- Update: Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial (MInT) Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. link to original article contains protocol PubMed
- Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. link to original article contains verified protocol PubMed
- Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP; Southwest Oncology Group. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol. 2008 May 10;26(14):2258-63. Epub 2008 Apr 14. link to original article contains verified protocol PubMed
- Vitolo U, Chiappella A, Ferreri AJ, Martelli M, Baldi I, Balzarotti M, Bottelli C, Conconi A, Gomez H, Lopez-Guillermo A, Martinelli G, Merli F, Novero D, Orsucci L, Pavone V, Ricardi U, Storti S, Gospodarowicz MK, Cavalli F, Sarris AH, Zucca E. First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. J Clin Oncol. 2011 Jul 10;29(20):2766-72. Epub 2011 Jun 6. link to original article contains verified protocol PubMed
- Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari A, Fragasso A, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012 Apr;53(4):581-8. Epub 2011 Nov 15. link to original article contains verified protocol PubMed
- Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. link to original article PubMed
- Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquières H, Hacini M, Fruchart C, Ysebaert L, Fermé C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. Epub 2013 Apr 9. link to original article contains verified protocol PubMed
- Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. link to original article contains verified protocol PubMed
- Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale M, Younes A, Rodriguez MA, Orlowski RZ, Wang M, Ouzounian ST, Samaniego F, Fayad L. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol. 2013 Dec;163(5):611-20. Epub 2013 Oct 1. link to original article contains verified protocol PubMed
- Seymour JF, Pfreundschuh M, Trnený M, Sehn LH, Catalano J, Csinady E, Moore N, Coiffier B; MAIN Study Investigators. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes. Haematologica. 2014 Aug;99(8):1343-9. Epub 2014 Jun 3. link to original article PubMed
- Retrospective: Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. link to original article PubMed
- Offner F, Samoilova O, Osmanov E, Eom HS, Topp MS, Raposo J, Pavlov V, Ricci D, Chaturvedi S, Zhu E, van de Velde H, Enny C, Rizo A, Ferhanoglu B. Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood. 2015 Oct 15;126(16):1893-901. Epub 2015 Jul 31. link to original article link to PMC article contains verified protocol PubMed
R-CHOP Intensified
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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Synonyms: R-CHOP-14, Dose-dense rituximab-CHOP
Structured Concept: none
Regimen #1
Study | Evidence | Comparator |
Pfreundschuh et al. 2014 (SEXIE-R-CHOP-14) | Randomized Phase II | See below |
Main CHOP-14 regimen
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Rituximab
Two arms were assessed; results are pending from this comparison. These higher doses were for males, only.
- Rituximab (Rituxan) 500 mg/m2 IV once every two weeks
OR
- Rituximab (Rituxan) 500 mg/m2 IV once on days -1, 0, 3, 7, 14, 21, 28, 42
14-day cycles x 6 cycles (8 doses of rituximab regardless of total number of CHOP-14 cycles)
Regimen #2
Study | Evidence | Comparator | Efficacy |
Delarue et al. 2013 (LNH03-6B) | Phase III | R-CHOP21 | Seems not superior |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
CNS prophylaxis:
- Methotrexate (MTX) 15 mg IT once every 14 days x 4 total doses
Supportive medications:
- Granulocyte colony-stimulating factor or pegylated G-CSF "according to the treating doctor's decision, fulfilling existing guidelines and product labelling at that time."
14-day cycles x 8 cycles
Regimen #3
Study | Evidence | Comparator | Efficacy |
Cunningham et al. 2013 | Phase III | R-CHOP-21 | Seems not superior |
Main R-CHOP-14 regimen
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- 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
- Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
CNS prophylaxis: Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
- Methotrexate (MTX) 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
Supportive medications:
- Lenograstim (Granocyte) (dose/route not specified) given on days 4 to 12
- Allopurinol (Aloprim) 300 mg PO once per day during cycle 1
- Co-trimoxazole 480 mg (route not specified) BID on 3 days per week, taken throughout therapy, ending 2 weeks after treatment is completed
14-day cycles x 6 cycles; then give additional doses of rituximab as described below
Additional doses of Rituximab
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
14-day cycles x 2 cycles
Regimen #4
Study | Evidence | Comparator |
Pfreundschuh et al. 2008 (RICOVER-60) | Phase III | CHOP-14 |
Pre-phase treatment
- Vincristine (Oncovin) 1 mg IV once (day not specified)
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 7
7-day course, then proceed to main R-CHOP-14 regimen
Main regimen
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications:
- Filgrastim (Neupogen) or Lenograstim (Granocyte) (dose/route/frequency not specified) starting on day 4, to continue until count recovery
14-day cycles x 6 to 8 cycles (8 doses of rituximab regardless of total number of cycles)
Radiation therapy for initial bulky disease
"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter =7.5 cm) or extranodal involvement"
- Radiation therapy, 36 Gy to areas of initial bulky disease
Regimen #5
Study | Evidence |
Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14) | Phase II |
Pre-phase treatment
- Vincristine (Oncovin) 1 mg IV once (day not specified)
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 7
7-day course, then proceed to main SMARTE-R-CHOP-14 regimen
Main regimen
- Rituximab (Rituxan) 375 mg/m2 IV once on days -4, 0, 10, 29, 57, 99, 155, and 239 (independent of CHOP cycles)
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
- Vincristine (Oncovin) 2 mg IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications:
- Filgrastim (Neupogen) or Lenograstim (Granocyte) (dose/route/frequency not specified) starting on day 4, to continue until count recovery
14-day cycles x 6 cycles
Radiation therapy for initial bulky disease
"Initial bulky disease": patients with "lymphoma masses or conglomerates with a diameter =7.5 cm) or extranodal involvement"
- Radiation therapy, 36 Gy to areas of initial bulky disease
References
- Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. link to original article contains verified protocol PubMed
- Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquières H, Hacini M, Fruchart C, Ysebaert L, Fermé C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. Epub 2013 Apr 9. link to original article contains verified protocol PubMed
- Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. link to original article contains verified protocol PubMed
- Abstract: Michael Pfreundschuh, Gerhard Held, Samira Zeynalova, Carsten Zwick, Mathias Haenel, Lorenz Truemper, Martin H. Dreyling, Judith Dierlamm, Markus Loeffler, Norbert Schmitz, Niels Murawski, German High-Grad Non-Hodgkin Lymphoma Study Group (DSHNHL). Increased rituximab (R) doses and effect on risk of elderly male patients with aggressive CD20+ B-cell lymphomas: Results from the SEXIE-R-CHOP-14 trial of the DSHNHL. J Clin Oncol 32:5s, 2014 (suppl; abstr 8501) link to original abstract
- Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N. Optimization of Rituximab for the Treatment of Diffuse Large B-Cell Lymphoma (II): Extended Rituximab Exposure Time in the SMARTE-R-CHOP-14 Trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. link to original article contains verified protocol PubMed
R-CHOP -> Ibritumomab tiuxetan
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R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence |
Witzig et al. 2015 (ECOG3402) | Phase II |
This regimen is intended for stage I-II DLBCL based on CT (not PET-CT) imaging.
Chemotherapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- 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 per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
21-day cycle x 4 to 6 cycles, followed in 3 to 12 weeks by:
Consolidation radioimmunotherapy
- Rituximab (Rituxan) 250 mg/m2 IV once per day on days 1 & 8
- Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 14.8 MBq/kg IV once on day 8
Patients with CT or PET positive disease 12 weeks after radioimmunotherapy underwent 30 Gy of IFRT.
References
- Witzig TE, Hong F, Micallef IN, Gascoyne RD, Dogan A, Wagner H Jr, Kahl BS, Advani RH, Horning SJ. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402. Br J Haematol. 2015 Sep;170(5):679-86. Epub 2015 May 14. link to original article contains verified protocol PubMed
R-CVP
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R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone
Structured Concept: C63473 (NCI-T), C1882520 (NCI-MT/UMLS)
Regimen
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
21-day cycles x up to 8 cycles
References
R-GCVP
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R-GCVP: Rituximab, Gemcitabine, Cyclophosphamide, Vincristine, Prednisolone
Regimen
Study | Evidence |
Fields et al. 2013 | Phase II |
Intended for use in patients unlikely to tolerate anthracyclines due to cardiac comorbidity.
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) as follows:
- Cycle 1: 750 mg/m2 IV over 30 minutes once per day on days 1 & 8
- Cycle 2: 875 mg/m2 IV over 30 minutes once per day on days 1 & 8
- Cycles 3 to 6: 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once on day 1
- Prednisolone (Millipred) 100 mg PO once per day on days 1 to 5
Supportive medications:
- Acetaminophen (Tylenol) 1000 mg (route not specified) prior to Rituximab (Rituxan)
- Chlorpheniramine (Chlor-Trimeton) 10 mg IV prior to Rituximab (Rituxan)
- Pegfilgrastim (Neulasta) 6 mg SC once on day 9
CNS prophylaxis:
- Methotrexate (MTX) 12.5 mg IT x 3 cycles (timing not specified) for patients at high risk of CNS relapse
21-day cycle x 6 cycles
References
- Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P, Jack A, El-Mehidi N, Johnson PW, Radford J, Linch DC, Cunnningham D. De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United kingdom national cancer research institute trial. J Clin Oncol. 2014 Feb 1;32(4):282-7. Epub 2013 Nov 12. link to original article contains verified protocol PubMed
R-HyperCVAD/R-MA
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R-HCVAD: Rituximab, Hyperfractionated Cyclophosphamide, Vincristine, Adriamycin (Doxorubicin), Dexamethasone
R-MA: Rituximab, Methotrexate, Ara-C (Cytarabine)
Regimen
Study | Evidence | Comparator | Efficacy |
Oki et al. 2013 | Phase III | R-CHOP | Seems to have increased CRR |
Intended for high-risk DLBCL (IPI ≥3). The authors report "excellent outcome" in patients ≤45 years old, however patients >45 years old had "unacceptable mortality."
Part A (cycles 1, 3, 5)
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 300 mg/m2 IV Q12H on days 1 to 3 (6 total doses)
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg) IV once per day on days 5 & 12
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 5
- Dexamethasone (Decadron) 40 mg PO/IV once per day on days 2 to 5
Supportive care:
- Mesna (Mesnex) 600 mg/m2/day IV continuous infusion on days 1 to 3
- Filgrastim (Neupogen) or Pegfilgrastim (Neulasta) starting 24 to 48 hours after completion of chemotherapy
- Ciprofloxacin (Cipro) 500 mg PO BID for 10 days after chemotherapy
- Fluconazole (Diflucan) 100 mg PO once per day for 10 days after chemotherapy
- Valacyclovir (Valtrex) 500 mg PO once per day for 10 days after chemotherapy
Dose modifications:
- Vincristine (Oncovin) reduced once by 50% for NCI common toxicity criteria Grade 2+ peripheral neuropathy, omitted if Grade 2+ peripheral neuropathy persists
- Doxorubicin (Adriamycin) and Cyclophosphamide (Cytoxan) reduced by 20% in subsequent A cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC <0.75 × 10^9/L or platelet count <75 × 10^9/L on day 21
Next cycle to start once ANC count is ≥1 x 10^9/L and platelet count is ≥100 x 10^9/L.
Although the protocol does not specify, it is assumed that if these thresholds are not met by day 21, the next cycle will start with the dose reductions as specified.
Part B (cycles 2, 4, 6)
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Methotrexate (MTX) 200 mg/m2 IV over 2 hours then 800 mg/m2 IV over 22 hours on day 1
- Cytarabine (Cytosar) 3000 mg/m2 IV over 2 hours Q12H on days 3 & 4 (4 total doses)
Supportive care:
- Folinic acid (Leucovorin) (dose/timing not specified) until serum methotrexate level <0.1 µM
- Sodium bicarbonate 1300 mg PO BID until methotrexate level <0.1 µM
- Filgrastim (Neupogen) or Pegfilgrastim (Neulasta) starting 24 to 48 hours after completion of chemotherapy
- Ciprofloxacin (Cipro) 500 mg PO BID for 10 days after chemotherapy
- Fluconazole (Diflucan) 100 mg PO once per day for 10 days after chemotherapy
- Valacyclovir (Valtrex) 500 mg PO once per day for 10 days after chemotherapy
Dose modifications:
- Methotrexate (MTX) reduced by 25% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC < 0.75 × 10^9/L or platelet count < 75 × 10^9/L on day 21
- Cytarabine (Cytosar) reduced by 33% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC < 0.75 × 10^9/L or platelet count < 75 × 10^9/L on day 21
21-day cycles
CNS prophylaxis: "recommended in patients with paraspinal disease, paranasal sinus disease, testicular disease, bone marrow disease, diffuse osseous disease or ≥2 sites of extranodal disease. Actual administration of prophylactic intrathecal chemotherapy was at the treating physician's discretion."
References
- Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale M, Younes A, Rodriguez MA, Orlowski RZ, Wang M, Ouzounian ST, Samaniego F, Fayad L. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol. 2013 Dec;163(5):611-20. Epub 2013 Oct 1. link to original article contains verified protocol PubMed
- Retrospective: Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. link to original article PubMed
R-MegaCHOP
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R-MegaCHOP: Rituximab, Mega, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence |
Pardal et al. 2014 | Phase II |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 1500 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 65 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
- Prednisone (Sterapred) 60 mg/m2 once per day on days 1 to 5
Supportive medications:
- Pegfilgrastim (Neulasta) given after each cycle
21-day cycle x 3 cycles
Patients with a negative PET-CT after 3 cycles received another 3 cycles of R-MegaCHOP for a total of 6 cycles; others underwent intensification of treatment with R-IFE.
References
- Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. link to original article contains verified protocol PubMed
R-miniCEOP
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R-miniCEOP: Rituximab, mini, Cyclophosphamide, Epirubicin, O?? (vinblastine), Prednisone
Regimen
Study | Evidence | Comparator | Efficacy |
Merli et al. 2012 (ANZINTER3) | Phase III | R-CHOP | Equivalent RR |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Vinblastine (Velban) 5 mg/m2 IV once on day 1
- Prednisone (Sterapred) 50 mg/m2 PO/IV once per day on days 1 to 5
Supportive medications:
- Prophylactic G-CSF used for persisting grade 4 neutropenia or febrile neutropenia.
- Cotrimoxazole (dose/route/schedule not specified) prophylaxis.
- Erythropoietin use was allowed for hemoglobin <11 g/dL.
21-day cycles x 6 cycles
Radiation therapy
"At the end of chemotherapy, radiotherapy (RT) was scheduled for sites of previous bulky disease or partially responding sites."
References
- Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari A, Fragasso A, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012 Apr;53(4):581-8. Epub 2011 Nov 15. link to original article contains verified protocol PubMed
R-miniCHOP
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R-miniCHOP: Rituximab, mini, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence |
Peyrade et al. 2011 | Phase II |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 400 mg/m2 IV once on day 1
- Doxorubicin (Adriamycin) 25 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1 mg IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
- No dose adjustments for hematologic toxicity. If needed, the subsequent R-miniCHOP cycle was postponed until neutrophil count was = 1.0 x 109/L and platelet count was = 100 x 109/L, with a maximum of 28 days between cycles. Treatment was stopped if patients' counts were not adequate within 28 days.
Supportive medications:
- "Prevention of tumour lysis syndrome by alkalinisation or hypouricaemic drugs was done if necessary."
- Serotonin (5-HT3) antagonist given every cycle.
- Prophylactic G-CSF or erythropoietin was left to treating physician's discretion.
- Patients with severe neutropenia or neutropenic fever received G-CSF (dose not specified) SQ on days 6 to 13 of the subsequent cycle until neutrophils were = 1.0 x 109/L.
21-day cycles x 6 cycles
References
- Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S, Coiffier B, Haioun C, Bologna S, Fitoussi O, Lepeu G, Fruchart C, Bordessoule D, Blanc M, Delarue R, Janvier M, Salles B, André M, Fournier M, Gaulard P, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte (GELA) investigators. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2011 May;12(5):460-8. link to original article contains verified protocol PubMed
R2CHOP, LR-CHOP-21
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R2CHOP: Rituximab, Revlimid (Lenalidomide), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
LR-CHOP-21: Lenalidomide, Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen #1
Study | Evidence |
Vitolo et al. 2014 (REAL07) | Phase II |
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 14
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- 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 per cycle) IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
CNS prophylaxis for "at risk" patients:
- Methotrexate (MTX) 12 mg IT once on day 1 of first 4 cycles
Supportive medications:
- Granulocyte colony-stimulating factors (dose/duration not specified)
- Low-molecular-weight heparins (dose/duration not specified)
- Trimethoprim/Sulfamethoxazole (Bactrim DS) or Pentamidine (Nebupent) (dose/duration not specified)
- Lamivudine (Epivir) (dose/duration not specified) for carriers of hepatitis B virus
21-day cycles x 6 cycles
Regimen #2
Study | Evidence |
Nowakowski et al. 2014 | Phase II |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 10
- 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 per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg/m2 PO once per day on days 1 to 5
Supportive medications:
- Pegfilgrastim (Neulasta) 6 mg SC once on day 2
- Aspirin 81 mg PO once per day unless on therapeutic dose Warfarin (Coumadin) or low molecular weight heparin
21-day cycles x up to 6 cycles
Regimen #3
Study | Evidence |
Chiappella et al. 2013 | Phase II |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Lenalidomide (Revlimid) 15 mg PO once per day on days 1 to 14
- 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 per cycle) IV once on day 1
- Prednisone (Sterapred) 40 mg/m2 PO once per day on days 1 to 5
Supportive medications:
- Granulocyte colony-stimulating factors (dose/duration not specified)
- Low-molecular-weight heparins (dose/duration not specified)
- Trimethoprim/Sulfamethoxazole (Bactrim DS) or Pentamidine (Nebupent)
- Lamivudine (Epivir) for occult hepatitis B carriers
21-day cycles x 6 cycles
References
- Nowakowski GS, LaPlant B, Habermann TM, Rivera CE, Macon WR, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Klebig RR, Reeder CB, Witzig TE. Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study. Leukemia. 2011 Dec;25(12):1877-81. Epub 2011 Jul 1. link to original article contains verified protocol PubMed
- Chiappella A, Tucci A, Castellino A, Pavone V, Baldi I, Carella AM, Orsucci L, Zanni M, Salvi F, Liberati AM, Gaidano G, Bottelli C, Rossini B, Perticone S, De Masi P, Ladetto M, Ciccone G, Palumbo A, Rossi G, Vitolo U. Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated elderly diffuse large B-cell lymphoma patients: phase I study by the Fondazione Italiana Linfomi. Haematologica. 2013 Nov;98(11):1732-8. Epub 2013 Jun 28. link to original article contains verified protocol PubMed
- Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G, Spina M, Pavone V, Ladetto M, Liberati AM, Molinari AL, Zinzani P, Salvi F, Fattori PP, Zaccaria A, Dreyling M, Botto B, Castellino A, Congiu A, Gaudiano M, Zanni M, Ciccone G, Gaidano G, Rossi G; on behalf of the Fondazione Italiana Linfomi. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):730-7. Epub 2014 May 12. link to original article contains verified protocol PubMed
- Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD, Thompson CA, Rivera CE, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Gascoyne RD, Habermann TM, Witzig TE. Lenalidomide Combined With R-CHOP Overcomes Negative Prognostic Impact of Non-Germinal Center B-Cell Phenotype in Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Phase II Study. J Clin Oncol. 2015 Jan 20;33(3):251-7. Epub 2014 Aug 18. link to original article contains verified protocol PubMed
VR-CHOP
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VR-CHOP: Velcade (Bortezomib), Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
Regimen
Study | Evidence |
Ruan et al. 2010 | Phase II |
Doses here are the phase II dose of bortezomib and the R-CHOP protocol as specified in the phase I report by Furman et al. 2010
- Bortezomib (Velcade) 1.3 mg/m2 (route not specified) once per day on days 1 & 4 (day 1 administered prior to R-CHOP)
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- 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 per cycle) IV once on day 1
- Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5
Supportive medications:
- "Standard" Acetaminophen (Tylenol) and Diphenhydramine (Benadryl) prior to Rituximab (Rituxan)
21-day cycle x 6 cycles
References
- Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, Lacasce A, Morrison J, Elstrom R, Ely S, Chadburn A, Cesarman E, Coleman M, Leonard JP. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Feb 20;29(6):690-7. Epub 2010 Dec 28. link to original article contains verified protocol PubMed
Consolidation and/or maintenance after upfront therapy
Observation
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Regimen
Study | Evidence | Comparator | Efficacy |
Jaeger et al. 2015 (NHL13) | Phase III | Rituximab | Seems not superior |
Witzens-Harig et al. 2015 (HD2002) | Phase III | Rituximab | Inferior OS in males |
No further treatment, also variously termed "observation" and "watchful waiting". Preceded by "standard treatment" in HD2002.
References
- Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. link to original article contains verified protocol PubMed
- Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. link to original article PubMed
- Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Ben Yehuda D, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsiao LT, Au WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klingler A, Chott A, Fridrik MA, Greil R. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica. 2015 Jul;100(7):955-63. Epub 2015 Apr 24. link to original article contains verified protocol PubMed
- Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Krämer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma. Results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Oct 9. [Epub ahead of print] link to original article PubMed
Rituximab (Rituxan)
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Regimen #1
Study | Evidence | Comparator | Efficacy |
Jaeger et al. 2015 (NHL13) | Phase III | Observation | Seems not superior |
Treatment preceded by 8 infusions of rituximab (375 mg/m2) and 4 to 8 cycles of CHOP-like chemotherapy. Patients required to be in CR or CRu prior to enrollment. The protocol was amended after the first 69 patients enrolled to increase length of treatment from 1 to 2 years.
- Rituximab (Rituxan) 375 mg/m2 IV once every 2 months
1 to 2 year course
Regimen #2
Study | Evidence | Comparator | Efficacy |
Witzens-Harig et al. 2015 (HD2002) | Phase III | Observation | Superior OS in males |
Preceded by "standard treatment" which was not further described in the paper, beyond that a majority of patient received R-CHOP (see Tables).
- Rituximab (Rituxan) 375 mg/m2 IV once every 3 months
2 year course
References
- Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. link to original article contains verified protocol PubMed
- Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. link to original article PubMed
- Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Ben Yehuda D, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsiao LT, Au WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klingler A, Chott A, Fridrik MA, Greil R. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica. 2015 Jul;100(7):955-63. Epub 2015 Apr 24. link to original article contains verified protocol PubMed
- Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Krämer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma. Results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Oct 9. [Epub ahead of print] link to original article contains verified protocol PubMed
Relapsed/refractory
Blinatumomab (Blincyto)
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Regimen
Study | Evidence |
Viardot et al. 2014 | Phase II |
Two dosing schemas were evaluated; this is the preferred dosing regimen, per the authors.
- Blinatumomab (Blincyto) as follows:
- 9 µg/day IV continuous infusion during week 1, then
- 28 µg/day IV continuous infusion during week 2, then
- 112 µg/day IV continuous infusion for remainder of the 8-week course
Supportive medications:
- Dexamethasone (Decadron) 40 mg (route not specified) before infusion start and 40 mg (route not specified) at infusion start; 24 mg/day (route not specified) on days 1, 2, 8, 15
8-week course, with option for responders to receive a 4-week consolidation cycle after a 4-week treatment-free period.
References
- Abstract: Andreas Viardot, Mariele Goebeler, Georg Hess, Svenja Neumann, Michael Pfreundschuh, Nicole Adrian, Florian Zettl, Martin Libicher, Evelyn Degenhard, Julia Stieglmaier, Alicia Zhang, Dirk Nagorsen and Ralf C. Bargou. Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma with the Bispecific T-Cell Engager (BiTE®) Antibody Construct Blinatumomab: Primary Analysis Results from an Open-Label, Phase 2 Study. ASH Annual Meeting 2014, Abstract 4460 link to abstract
BR
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BR: Bendamustine, Rituximab
Regimen
Study | Evidence | ||
Ohmachi et al. 2013 | Phase II | ||
Vacirca et al. 2013 | Phase II |
Bendamustine was given on days 2 & 3 by Ohmachi et al. and on days 1 & 2 by Vacirca et al.
- Bendamustine (Treanda) 120 mg/m2 IV over 60 minutes once per day on days 1 & 2 OR on days 2 & 3
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Supportive medications:
- "Opportunistic infection prophylaxis with Trimethoprim/Sulfamethoxazole (Bactrim DS) and Acyclovir (Zovirax) was recommended."
21-day cycles x up to 6 cycles
References
- Ohmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, Takahashi N, Takahashi N, Uike N, Eom HS, Chae YS, Terauchi T, Tateishi U, Tatsumi M, Kim WS, Tobinai K, Suh C, Ogura M. Multicenter Phase II Study of Bendamustine Plus Rituximab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2013 Jun 10;31(17):2103-9. Epub 2013 May 6. link to original article contains verified protocol PubMed
- Vacirca JL, Acs PI, Tabbara IA, Rosen PJ, Lee P, Lynam E. Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann Hematol. 2014 Mar;93(3):403-9. Epub 2013 Aug 17. link to original article contains verified protocol PubMed
Brentuximab vedotin (Adcetris)
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Regimen
Study | Evidence | ||
Bartlett et al. 2014 | Phase II | ||
Jacobsen et al. 2015 | Phase II |
Bartlett et al. treated patients with undetectable CD30 by visual assessment using routine IHC. Jacobsen et al. treated patients with CD30+ non-Hodgkin lymphoma, as determined by IHC.
- Brentuximab vedotin (Adcetris) 1.8 mg/kg IV over 30 minutes on day 1
21-day cycles, given until progression or unacceptable toxicity
References
- Abstract: Nancy L. Bartlett, MD, Mitchell R. Smith, MD, Ranjana Advani, MD, Tatyana Feldman, MD, Kerry J. Savage, MD MSc, Maria Corinna Palanca-Wessels, MD, PhD and Tanya Siddiqi, MD. Brentuximab Vedotin Monotherapy in DLBCL Patients with Undetectable CD30: Preliminary Results from a Phase 2 Study. ASH Annual Meeting 2014 Abstract 629 link to abstract
- Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NL. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015 Feb 26;125(9):1394-402. Epub 2015 Jan 8. link to original article contains verified protocol PubMed
DHAP
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DHAP: Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Evidence | Comparator |
Velasquez et al. 1988 | Phase II | |
Philip et al. 1995 (PARMA) | Phase III | DHAP x 2 -> BEAC |
- Dexamethasone (Decadron) 40 mg IV over 15 minutes once per day on days 1 to 4
- Cytarabine (Cytosar)
- 2000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses) in patients younger than 70
- 1000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses) in patients older than 70
- Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1
Supportive medications:
- Metoclopramide (Reglan) 1 mg/kg (route and frequency not indicated)
- Diphenhydramine (Benadryl) 25 mg IV (frequency not indicated)
3 to 4 week cycle "according to the extent of myelosuppression"
Velasquez et al. 1988 report 6 to 10 courses, usually 4 courses beyond maximum response. The PARMA trial collected bone marrow after cycle 1 and then randomized responders (PR/CR) after cycle 2 to 4 more courses of DHAP versus autologous stem-cell transplant (ASCT).
References
- Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. link to original article contains verified protocol PubMed
- Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. link to original article does not contain protocol PubMed
EPOCH
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EPOCH: Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin
Synonyms: CHEOP, DA-EPOCH
Structured Concept: C63779 (NCI-T), C1880475 (NCI-MT/UMLS)
Regimen
Study | Evidence |
Wilson et al. 1993 | Phase II |
- Etoposide (Vepesid) 50 mg/m2/day (total dose of 200 mg/m2) IV continuous infusion on days 1 to 4
- Prednisone (Sterapred) 60 mg/m2 PO on days 1 to 6
- Vincristine (Oncovin) 0.4 mg/m2/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1 to 4
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 6
- Doxorubicin (Adriamycin) 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1 to 4
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SQ once per day, starting on day 6 and continuing until ANC >5,000/uL past nadir
- PCP prophylaxis with any one of the following:
- Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO BID 3 days per week
- Atovaquone (Mepron) 1500 mg PO once per day
- Pentamidine (Nebupent) 300 mg nebulized every 28 days
21-day cycles x 6 to 8 cycles
References
- Wilson WH, Bryant G, Bates S, Fojo A, Wittes RE, Steinberg SM, Kohler DR, Jaffe ES, Herdt J, Cheson BD et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993 Aug;11(8):1573-82 link to original article contains verified protocol PubMed
ESHAP
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ESHAP: Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Evidence | Comparator | Efficacy |
Velasquez et al. 1994 | Phase III | ESHA | Superior RR |
Avilés et al. 2010 | Phase III | R-ESHAP | Seems not superior |
- Etoposide (Vepesid) 40 mg/m2 IV over 1 hour once per day on days 1 to 4
- Methylprednisolone (Solumedrol) 250-500 mg IV over 15 minutes once per day on days 1 to 5
- Cytarabine (Cytosar) 2000 mg/m2 IV over 2 hours once on day 5
- Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion on days 1 to 4 (total dose per cycle: 100 mg/m2)
Supportive medications:
- At least 1 liter normal saline with 25 to 50 g Mannitol once per day throughout chemotherapy
- Metoclopramide (Reglan) 0.5 to 1 mg/kg "given regularly"
21 to 28 day cycles ("after recovery of the toxic effects") x 6 to 8 cycles
References
- Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. link to original article contains verified protocol PubMed
- Avilés A, Neri N, Huerta-Guzmán J, de Jesús Nambo M. ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2010 Apr;10(2):125-8. link to original article PubMed
Everolimus (Afinitor)
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Regimen
Study | Evidence |
Witzig et al. 2011 | Phase II |
- Everolimus (Afinitor) 10 mg PO once per day on an empty stomach
Supportive medications:
- "Patients could receive white blood cell growth factors, if neutropenia developed at physician's discretion. Erythropoietin treatment for anemia was permitted per standard guidelines."
28-day cycles, given until progression or unacceptable toxicity
References
- Witzig TE, Reeder CB, LaPlant BR, Gupta M, Johnston PB, Micallef IN, Porrata LF, Ansell SM, Colgan JP, Jacobsen ED, Ghobrial IM, Habermann TM. A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia. 2011 Feb;25(2):341-7. Epub 2010 Dec 7. link to original article contains verified protocol PubMed
Everolimus & Rituximab
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Regimen
Study | Evidence |
Barnes et al. 2013 | Phase II |
- Everolimus (Afinitor) 5 mg PO once per day on days 1 to 14, increased to 10 mg PO once per day for the remainder of cycle 1 and thereafter, if tolerated
- Rituximab (Rituxan) 375 mg/m2 IV once per week x 4 weeks, then once on day 1 of cycle 2 onwards
28-day cycles x 6 cycles Responders had the option of continuing everolimus for another 6 months.
References
- Barnes JA, Jacobsen E, Feng Y, Freedman A, Hochberg EP, LaCasce AS, Armand P, Joyce R, Sohani AR, Rodig SJ, Neuberg D, Fisher DC, Abramson JS. Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma. Haematologica. 2013 Apr;98(4):615-9. Epub 2012 Nov 9. link to original article contains verified protocol PubMed
Gemcitabine (Gemzar)
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Regimen
Study | Evidence |
Fosså et al. 1999 | Phase II |
- Gemcitabine (Gemzar) as follows:
- Cycle 1: 1250 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
- Subsequent cycles (if no hematologic or nonhematologic toxicities): Optional increase to 1500 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
4-week cycles until progression or intolerance
References
- Fosså A, Santoro A, Hiddemann W, Truemper L, Niederle N, Buksmaui S, Bonadonna G, Seeber S, Nowrousian MR. Gemcitabine as a single agent in the treatment of relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3786-92. link to original article contains verified protocol PubMed
- Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed
GVD
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GVD: Gemcitabine, Vinorelbine, Doxil (Doxorubicin liposomal)
Regimen
Study | Evidence |
Bai et al. 2013 | Retrospective |
- Gemcitabine (Gemzar) 800 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 15 mg/m2 IV once on day 1
- Doxorubicin liposomal (Doxil) 20 mg/m2 IV once on day 1
14-day cycles
References
- Retrospective: Bai B, Huang HQ, Cai QQ, Wang XX, Cai QC, Lin ZX, Gao Y, Xia Y, Bu Q, Guo Y. Promising long-term outcome of gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in 14-day schedule as salvage regimen for patients with previously heavily treated Hodgkin's lymphoma and aggressive non-Hodgkin's lymphoma. Med Oncol. 2013 Mar;30(1):350. Epub 2013 Jan 18. link to original article contains protocol PubMed
Ibrutinib (Imbruvica)
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Regimen
Study | Evidence |
Wilson et al. 2012 | Phase II |
Clinically meaningful responses were observed in the ABC subtype, only. Further clinical trials are currently underway.
- Ibrutinib (Imbruvica) 560 mg PO once per day
Duration not specified
References
- Abstract: Wyndham H. Wilson, MD, PhD, John F. Gerecitano, MD, PhD, Andre Goy, MD, Sven de Vos, MD, PhD, Vaishalee P. Kenkre, MD, Paul M. Barr, MD, Kristie A. Blum, MD, Andrei R. Shustov, MD, Ranjana H. Advani, MD, Jason Lih, PhD, Mickey Williams, PhD, Roland Schmitz, PhD, Yandan Yang, PhD, Stefania Pittaluga, MD, PhD, George Wright, PhD, Lori A. Kunkel, MD, Jesse McGreivy, MD, Sriram Balasubramanian, PhD, Mei Cheng, PhD, Davina Moussa, Joseph J. Buggy, PhD and Louis M. Staudt, MD, PhD. The Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), Has Preferential Activity in the ABC Subtype of Relapsed/Refractory De Novo Diffuse Large B-Cell Lymphoma (DLBCL): Interim Results of a Multicenter, Open-Label, Phase 2 Study. Blood 120, a686 (2012). link to abstract
ICE
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ICE: Ifosfamide, Carboplatin, Etoposide
Regimen
Study | Evidence |
Zelenetz et al. 2003 | Phase II |
Third cycle intended to be followed by peripheral blood stem cell collection
- Ifosfamide (Ifex) 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with mesna
- Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg per cycle) IV bolus once on day 2
- Carboplatin AUC calculated based on a 12-hour creatinine clearance
- Etoposide (Vepesid) 100 mg/m2 IV bolus once per day on days 1 to 3
14-day cycles x 3 cycles
Supportive medications:
- Mesna (Mesnex) 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with Ifosfamide (Ifex)
- Filgrastim (Neupogen) 5 µg/kg SC once per day on days 5 to 12 (10 µg/kg with cycle 3, given until collection of peripheral blood stem cells)
References
- Zelenetz AD, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz CH. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003;14 Suppl 1:i5-10. link to original article contains verified protocol PubMed
- Hertzberg MS, Crombie C, Benson W, Taper J, Gottlieb D, Bradstock KF. Outpatient-based ifosfamide, carboplatin and etoposide (ICE) chemotherapy in transplant-eligible patients with non-Hodgkin's lymphoma and Hodgkin's disease. Ann Oncol. 2003;14 Suppl 1:i11-6. link to original article PubMed
Ifosfamide (Ifex)
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Regimen
Study | Evidence | Comparator | |
Case et al. 1991 (CALGB 8552) | Phase II | ||
Pettengell et al. 2012 | Phase III, <20 in this arm | Pixantrone |
Dose & schedule is as given in Pettengell et al. CALGB 8552 used a different dose & schedule.
- Ifosfamide (Ifex) 3000 mg/m2 IV once per day on days 1 & 2
Supportive medications:
- Mesna (Mesnex) dose not specified
28-day cycles
References
- Case DC Jr, Anderson J, Ervin TJ, Gottlieb A. Phase II trial of ifosfamide and mesna in previously treated patients with non-Hodgkin's lymphoma: Cancer and Leukemia Group B study 8552. Hematol Oncol. 1991 Jul-Oct;9(4-5):189-96. PubMed
- Review: Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. Review. link to original article PubMed
- Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed
Lenalidomide (Revlimid)
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Regimen
Study | Evidence | ||
Wiernik et al. 2008 (NHL-002) | Phase II | ||
Witzig et al. 2011 (NHL-003) | Phase II |
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
28-day cycles until disease progression or unacceptable toxicity
References
- Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008 Oct 20;26(30):4952-7. Epub 2008 Jul 7. link to original article contains verified protocol PubMed
- Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA, Bouabdallah R, Haioun C, Tilly H, Guo P, Pietronigro D, Ervin-Haynes AL, Czuczman MS. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol. 2011 Jul;22(7):1622-7. Epub 2011 Jan 12. link to original article contains verified protocol PubMed
Lenalidomide & Rituximab
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Regimen #1
Study | Evidence |
Zinzani et al. 2011 | Phase II |
Induction
- Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
- Rituximab (Rituxan) 375 mg/m2 IV once per day on days 1 & 21
28-day cycles x 4 cycles; patients with response of stable disease or better received:
Maintenance
- Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
28-day cycles x 8 months
Regimen #2
Study | Evidence |
Wang et al. 2013 | Phase II |
- Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
- Rituximab (Rituxan) 375 mg/m2 IV once per week on weeks 1 to 4 of cycle 1, only
28-day cycles
References
- Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):462-6. Epub 2011 May 4. link to original article contains verified protocol PubMed
- Update: Zinzani PL, Pellegrini C, Derenzini E, Argnani L, Pileri S. Long-term efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma patients. Hematol Oncol. 2013 Dec;31(4):223-4. Epub 2013 Apr 26. link to original article PubMed
- Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, Hagemeister F, Fanale M, Oki Y, Pro B, Shah J, Thomas S, Younes A, Hosing C, Zhang L, Newberry KJ, Desai M, Cheng N, Badillo M, Bejarano M, Chen Y, Young KH, Champlin R, Kwak L, Fayad L. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013 Sep;27(9):1902-9. Epub 2013 Apr 2. link to original article contains verified protocol PubMed
Mitoxantrone (Novantrone)
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Regimen
Study | Evidence |
Bajetta et al. 1988 | Phase II |
- Mitoxantrone (Novantrone) 14 mg/m2 IV over 30 minutes once on day 1
3-week cycles
References
- Bajetta E, Buzzoni R, Valagussa P, Bonadonna G. Mitoxantrone: an active agent in refractory non-Hodgkin's lymphomas. Am J Clin Oncol. 1988 Apr;11(2):100-3. contains protocol PubMed
- Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed
Obinutuzumab (Gazyva)
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Regimen
Study | Evidence |
Morschhauser et al. 2013 (GAUGUIN) | Phase II |
- Obinutuzumab (Gazyva) as follows:
- Cycle 1: 1600 mg (diluted to 10 mg/mL) IV once per day on days 1 & 8
- Cycles 2 to 8: 800 mg IV once on day 1
- Initial infusion rate is 50 mg/hour. In the absence of infusion-related reactions (IRRs), the rate is then increased by 50 mg/hour every 30 minutes, up to a maximum of 400 mg/hour.
Supportive medications:
- Acetaminophen (Tylenol) or paracetamol 650 to 1000 mg PO once 30 minutes prior to Obinutuzumab (Gazyva)
- "An antihistamine" 30 minutes prior to Obinutuzumab (Gazyva); if there were no infusion-related reactions (IRRs) requiring medication or infusion interruption, antihistamine could be omitted for subsequent infusions
- Premedication with corticosteroids recommended for patients at high risk of infusion-related reactions (IRRs)
- Use of G-CSF allowed for severe neutropenia
- Antibiotic prophylaxis allowed
21-day cycle x 8 cycles
References
- Morschhauser FA, Cartron G, Thieblemont C, Solal-Céligny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA. Obinutuzumab (GA101) Monotherapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma or Mantle-Cell Lymphoma: Results From the Phase II GAUGUIN Study. J Clin Oncol. 2013 Aug 10;31(23):2912-9. Epub 2013 Jul 8. link to original article contains verified protocol PubMed
O-DHAP
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O-DHAP: Ofatumumab, Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Evidence |
Matasar et al. 2013 | Phase II |
- Ofatumumab (Arzerra) as follows:
- Cycle 1: 1000 mg IV once per day on days 1 & 8
- Cycles 2 & 3: 1000 mg IV once on day 1
- Dexamethasone (Decadron) 40 mg PO/IV once per day on days 1 to 4
- Cytarabine (Cytosar) 2000 mg/m2 IV Q12H x 2 doses on day 2 (total of 2 doses)
- Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1
Supportive medications:
21-day cycle x 3 cycles
References
- Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. Epub 2013 May 21. link to original article contains verified protocol PubMed
O-ICE
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O-ICE: Ofatumumab, Ifosfamide, Carboplatin, Etoposide
Regimen
Study | Evidence |
Matasar et al. 2013 | Phase II |
- Ofatumumab (Arzerra) as follows:
- Cycle 1: 1000 mg IV once per day on days 1 & 8
- Cycles 2 & 3: 1000 mg IV once on day 1
- Ifosfamide (Ifex) 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with Mesna (Mesnex)
- Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg) IV once on day 1 OR 2 (1 dose, total)
- Carboplatin AUC calculated based on a 12-hour creatinine clearance
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Supportive medications:
- Mesna (Mesnex) 5000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with Ifosfamide (Ifex)
- G-CSF or Neulasta was recommended (no details given).
21-day cycle x 3 cycles
References
- Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. Epub 2013 May 21. link to original article contains verified protocol PubMed
Ofatumumab (Arzerra)
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Regimen
Study | Evidence |
Coiffier et al. 2013 (415 Study) | Phase II |
- Ofatumumab (Arzerra) 300 mg IV on cycle 1 day 1, then 1000 mg IV once per week x 7 weeks (total of 8 doses)
Supportive medications:
- Acetaminophen (Tylenol) 1000 mg or equivalent 30 min to 2 h prior to Ofatumumab (Arzerra)
- Cetirizine (Zyrtec) 10 mg PO or equivalent 30 min to 2 h prior to Ofatumumab (Arzerra)
- Prednisolone (Millipred) 100 mg (route not specified) or equivalent 30 min to 2 h prior to Ofatumumab (Arzerra) for first 2 infusions, only
One course
References
- Coiffier B, Radford J, Bosly A, Martinelli G, Barca G, Davies A, Decaudin D, Gallop-Evans E, Padmanabhan-Iyer S, Van Eygen K, Wu KL, Gupta IV, Lin TS, Goldstein N, Jewell RC, Winter P, Lisby S; 415 study investigators. A multicentre, phase II trial of ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma. Br J Haematol. 2013 Nov;163(3):334-42. Epub 2013 Aug 23. link to original article contains verified protocol PubMed
Oxaliplatin (Eloxatin)
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Regimen
Study | Evidence | Comparator | |
Germann et al. 1999 | Phase II | ||
Oki et al. 2005 | Phase II | ||
Pettengell et al. 2012 | Phase III, <20 in this arm | Pixantrone |
Germann et al. give a range of 100 to 130 mg/m2; Oki et al. used the 130 mg/m2 dosage; Pettengell et al. used the 100 mg/m2 dosage.
- Oxaliplatin (Eloxatin) 100 to 130 mg/m2 IV once on day 1
21-day cycles
References
- Germann N, Brienza S, Rotarski M, Emile JF, Di Palma M, Musset M, Reynes M, Soulié P, Cvitkovic E, Misset JL. Preliminary results on the activity of oxaliplatin (L-OHP) in refractory/recurrent non-Hodgkin's lymphoma patients. Ann Oncol. 1999 Mar;10(3):351-4. link to original article contains verified protocol PubMed
- Review: Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. Review. link to original article PubMed
- Oki Y, McLaughlin P, Pro B, Hagemeister FB, Bleyer A, Loyer E, Younes A. Phase II study of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma. Cancer. 2005 Aug 15;104(4):781-7. link to original article contains verified protocol PubMed
- Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed
Pixantrone (Pixuvri)
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Regimen
Study | Evidence | Comparator | Efficacy |
Pettengell et al. 2012 | Phase III | Etoposide Gemcitabine Ifosfamide Mitoxantrone Oxaliplatin Vinorelbine |
Seems to have superior RR |
- Pixantrone (Pixuvri) 85 mg/m2 IV once per day on days 1, 8, 15
28-day cycle x up to 6 cycles
References
- Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed
R-CVEP
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R-CVEP: Rituximab, Cyclophosphamide, Vorinostat, Etoposide, Prednisone
Regimen
Study | Evidence |
Straus et al. 2014 | Phase II |
The MTD for vorinostat was 300 mg in this phase I/II trial.
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV once per day on days 1 & 8
- Vorinostat (Zolinza) 300 mg PO once per day on days 1 to 10
- Etoposide (Vepesid) 70 mg/m2 IV once on day 1
- Prednisone (Sterapred) 60 mg/m2 PO once per day on days 1 to 10
28-day cycle x 6 cycles
References
- Straus DJ, Hamlin PA, Matasar MJ, Lia Palomba M, Drullinsky PR, Zelenetz AD, Gerecitano JF, Noy A, Hamilton AM, Elstrom R, Wegner B, Wortman K, Cella D. Phase I/II trial of vorinostat with rituximab, cyclophosphamide, etoposide and prednisone as palliative treatment for elderly patients with relapsed or refractory diffuse large B-cell lymphoma not eligible for autologous stem cell transplantation. Br J Haematol. 2015 Mar;168(5):663-70. Epub 2014 Oct 15. link to original article contains protocol PubMed
R-DexaBEAM
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R-DexaBEAM: Rituximab, Dexamethasone, BiCNU (Carmustine), Etoposide, Ara-C (Cytarabine), Melphalan
Regimen
Study | Evidence |
Kirschey et al. 2014 | Phase II |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 24 mg PO TID on days 1 to 10
- Carmustine (BiCNU) 60 mg/m2 IV once on day 2
- Etoposide (Vepesid) 75 mg/m2 IV once per day on days 4 to 7
- Cytarabine (Cytosar) 200 mg/m2 IV BID on days 4 to 7
- Melphalan (Alkeran) 20 mg/m2 IV once on day 3
3- to 4-week cycle x 2 cycles
Patient proceed to undergo high dose therapy and autologous stem cell transplant.
References
- Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains verified protocol PubMed
R-DHAP
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R-DHAP: Rituximab, Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen #1
Study | Evidence | Comparator | Efficacy |
Crump et al. 2014 (NCIC-CTG LY.12) | Phase III | R-GDP | Noninferior RR |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
- Cytarabine (Cytosar) 2000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
- Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1
21-day cycles x up to 3 cycles
Responders proceeded to stem-cell mobilization and autologous stem cell transplant.
Regimen #2
Study | Evidence | Comparator | Efficacy |
Gisselbrecht et al. 2010 (CORAL) | Phase III | R-ICE | Seems not superior |
Note: the paper makes reference to Velasquez et al. 1988 to describe this regimen, although this reference is for DHAP, not R-DHAP. The paper also contains the following regimen information:
- Rituximab (Rituxan) as follows (given first before other chemotherapy):
- Cycle 1: 375 mg/m2 IV once per day on days -1 & 1
- Cycle 2: 375 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
- Cytarabine (Cytosar) 2000 mg/m2 IV over 3 hours Q12H x 2 doses on day 2 (total of 2 doses)
- Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1
Supportive medications:
- G-CSF "depending on site policy, with R-DHAP, but always after the third cycle until the end of leukaphereses"
21-day cycles x 3 cycles
Patients with complete or partial response then received BEAM autologous stem-cell transplant.
Regimen #3
Study | Evidence |
Mey et al. 2006 | Phase II |
The doses here were used after a mid-protocol amendment pertaining to the first cycle.
First cycle
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 40 mg PO once per day on days 3 to 5
- Cytarabine (Cytosar) as follows:
- 1000 mg/m2 IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses) if younger than 60 years old
- 500 mg/m2 IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses) if older than 60 years old
- Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion on days 3 to 5
3-week cycle
Subsequent cycles
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Dexamethasone (Decadron) 40 mg PO once per day on days 3 to 6
- Cytarabine (Cytosar) as follows:
- 2000 mg/m2 IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses) if younger than 60 years old
- 1000 mg/m2 IV over 2 hours Q12H x 2 doses on day 4 (total of 2 doses) if older than 60 years old
- Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion on days 3 to 6
3-week cycle up to 3 cycles (4 cycles, total)
Patients with complete or partial response were allowed to undergo autologous stem-cell transplant.
References
- Hagberg H, Gisselbrecht C; CORAL study group. Randomised phase III study of R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by high-dose therapy and a second randomisation to maintenance treatment with rituximab or not: an update of the CORAL study. Ann Oncol. 2006 May;17 Suppl 4:iv31-2. link to original article PubMed
- Mey UJ, Orlopp KS, Flieger D, Strehl JW, Ho AD, Hensel M, Bopp C, Gorschlüter M, Wilhelm M, Birkmann J, Kaiser U, Neubauer A, Florschütz A, Rabe C, Hahn C, Glasmacher AG, Schmidt-Wolf IG. Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. Cancer Invest. 2006 Oct;24(6):593-600. link to original article contains verified protocol PubMed
- Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol PubMed
- Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains verified protocol PubMed
R-EPOCH
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R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
Regimen
Study | Evidence |
Jermann et al. 2004 | Phase II |
Note: this is not the dose-adjusted R-EPOCH regimen
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
- Etoposide (Vepesid) 65 mg/m2/day (total dose of 195 mg/m2) IV continuous infusion on days 2 to 4
- Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 14
- Vincristine (Oncovin) 0.5 mg/m2/day (total dose of 1.5 mg/m2) IV continuous infusion on days 2 to 4
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 5
- Doxorubicin (Adriamycin) 15 mg/m2/day (total dose of 45 mg/m2) IV continuous infusion on days 2 to 4
21-day cycles x 4 to 6 cycles
References
- Jermann M, Jost LM, Taverna Ch, Jacky E, Honegger HP, Betticher DC, Egli F, Kroner T, Stahel RA. Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Ann Oncol. 2004 Mar;15(3):511-6. link to original article contains verified protocol PubMed
R-ESHAP
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R-ESHAP: Rituximab, Etoposide, Solumedrol (Methylprednisolone) High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
Regimen
Study | Evidence | Comparator | Efficacy |
Martín et al. 2008 | Retrospective | ||
Avilés et al. 2010 | Phase III | ESHAP | Seems not superior |
Regimen details are based on ESHAP paper from 1994. Per retrospective review (Martin et al. 2008), 90% of patients given R-ESHAP received rituximab on day 1, 10% on day 5.
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1 (or day 5)
- Etoposide (Vepesid) 40 mg/m2 IV over 1 hour once per day on days 1 to 4
- Methylprednisolone (Solumedrol) 250 to 500 mg IV over 15 minutes once per day on days 1 to 5
- In Martín et al. 2008, methylprednisolone could either be given on days 1 to 4 or days 1 to 5, with patients receiving total doses of anywhere from 1000 mg per cycle to 2500 mg per cycle
- Cytarabine (Cytosar) 2000 mg/m2 IV over 2 hours once on day 5
- Cisplatin (Platinol) 25 mg/m2/day IV continuous infusion over 96 hours (total dose per cycle: 100 mg/m2) on days 1 to 4
Supportive medications:
- At least 1 liter normal saline with 25 to 50 g Mannitol once per day throughout chemotherapy
- Metoclopramide (Reglan) 0.5 to 1 mg/kg "given regularly"
21 to 28 day cycles ("after recovery of the toxic effects") x 6 to 8 cycles
References
- Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. link to original article contains verified protocol PubMed
- Retrospective: Martín A, Conde E, Arnan M, Canales MA, Deben G, Sancho JM, Andreu R, Salar A, García-Sanchez P, Vázquez L, Nistal S, Requena MJ, Donato EM, González JA, León A, Ruiz C, Grande C, González-Barca E, Caballero MD; Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO Cooperative Group). R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica. 2008 Dec;93(12):1829-36. Epub 2008 Oct 22. link to original article contains verified protocol PubMed
- Avilés A, Neri N, Huerta-Guzmán J, de Jesús Nambo M. ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2010 Apr;10(2):125-8. link to original article PubMed
R-GDP
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R-GDP: Rituximab, Gemcitabine, Dexamethasone, Platinol (Cisplatin)
Regimen #1
Study | Evidence | Comparator | Efficacy |
Crump et al. 2014 (NCIC-CTG LY.12) | Phase III | R-DHAP | Noninferior RR |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
21-day cycle x up to 3 cycles
Responders proceeded to stem-cell mobilization and autologous stem cell transplant.
Regimen #2
Study | Evidence |
Hou et al. 2012 | Non-randomized |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Dexamethasone (Decadron) 40 mg IV once per day on days 1 to 4
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1 to 3
21-day cycle x up to 6 cycles
References
- Hou Y, Wang HQ, Ba Y. Rituximab, gemcitabine, cisplatin, and dexamethasone in patients with refractory or relapsed aggressive B-cell lymphoma. Med Oncol. 2012 Dec;29(4):2409-16. Epub 2012 Apr 3. link to original article PubMed
- Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains verified protocol PubMed
R-GemOx
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R-GemOx: Rituximab, Gemcitabine, Oxaliplatin
Regimen #1 "GEMOX-R"
Study | Evidence |
López et al. 2008 | Phase II |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 100 mg/m2 IV once on day 1
21-day cycles x 6 to 8 cycles
Regimen #2
Study | Evidence |
El Gnaoui et al. 2007 | Phase II |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV at a fixed dose rate of 10 mg/m2/min once on day 2
- Oxaliplatin (Eloxatin) 100 mg/m2 IV over 2 hours once on day 2
Supportive medications:
- Methylprednisolone (Solumedrol) 1 mg/kg IV once prior to Rituximab (Rituxan)
- Acetaminophen (Tylenol) 1000 mg PO once prior to Rituximab (Rituxan)
- Dexchlorpheniramine (Polaramine) 6 mg PO once prior to Rituximab (Rituxan)
- Primary prophylaxis with G-CSF was not permitted
14-day cycles x up to 8 cycles
References
- El Gnaoui T, Dupuis J, Belhadj K, Jais JP, Rahmouni A, Copie-Bergman C, Gaillard I, Diviné M, Tabah-Fisch I, Reyes F, Haioun C. Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol. 2007 Aug;18(8):1363-8. Epub 2007 May 11. link to original article contains verified protocol PubMed
- López A, Gutiérrez A, Palacios A, Blancas I, Navarrete M, Morey M, Perelló A, Alarcón J, Martínez J, Rodríguez J. GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study. Eur J Haematol. 2008 Feb;80(2):127-32. Epub 2007 Nov 20. link to original article contains verified protocol PubMed
- Mounier N, El-Gnaoui T, Tilly H, Canioni D, Sebban C, Casasnovas RO, Delarue R, Sonet A, Beaussart P, Petrella T, Castaigne S, Bologna S, Salles G, Rahmouni A, Gaulard P, Haioun C. Rituximab plus gemcitabine and oxaliplatin in refractory/relapsed patients with diffuse large B-cell lymphoma who are not candidates for high-dose therapy. A phase II Lymphoma Study Association trial. Haematologica. 2013 Nov;98(11):1726-31. Epub 2013 Jun 10. link to original article contains verified protocol PubMed
R-ICE
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R-ICE: Rituximab, Ifosfamide, Carboplatin, Etoposide
Regimen #1
Study | Evidence | Comparator | Efficacy |
Gisselbrecht et al. 2010 (CORAL) | Phase III | R-DHAP | Seems not superior |
Note: the paper refers to the Kewalramani et al. 2004 regimen described below in variant #3, although it has slightly different day numbering. Doses are the same.
- Rituximab (Rituxan) as follows (given first before other chemotherapy):
- Cycle 1: 375 mg/m2 IV once per day on days -1 & 1
- Cycles 2 & 3: 375 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 5,000 mg/m2 IV continuous infusion over 24 hours on day 2
- Carboplatin (Paraplatin) AUC 5 IV (maximum dose of 800 mg per cycle) on day 2
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
Supportive medications:
- Mesna (Mesnex) given with Ifosfamide (Ifex); dose & schedule not specified in the paper
- " Granulocyte colony-stimulating factor was administered after R-ICE"
21-day cycles x 3 cycles
Patients with complete or partial response then received BEAM autologous stem-cell transplant.
Regimen #2
Study | Evidence |
Guo et al. 2014 | Phase II |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 1,600 mg/m2 IV once per day on days 2 to 4
- Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg per cycle) IV once on day 3
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 2 to 4
3 cycles; duration of cycles not specified in the abstract
Regimen #3
Study | Evidence | ||
Zelenetz et al. 2003 | Phase II | ||
Kewalramani et al. 2004 | Phase II |
Third cycle intended to be followed by peripheral blood stem cell collection
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- An additional one-time dose of Rituximab (Rituxan) 375 mg/m2 IV was given 48 hours before the beginning of cycle 1
- Ifosfamide (Ifex) 5,000 mg/m2 IV continuous infusion over 24 hours on day 4, mixed together with Mesna (Mesnex)
- Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg per cycle) IV bolus once on day 4
- Carboplatin AUC calculated based on a 12-hour creatinine clearance
- Etoposide (Vepesid) 100 mg/m2 IV bolus once per day on days 3 to 5
14-day cycles x 3 cycles
Supportive medications (as described by Kewalramani et al. 2004):
- Mesna (Mesnex) 5,000 mg/m2 IV continuous infusion over 24 hours on day 4, mixed together with Ifosfamide (Ifex)
- Acetaminophen (Tylenol) 650 mg PO once as premedication for Rituximab (Rituxan)
- Diphenhydramine (Benadryl) 50 mg IV once as premedication for Rituximab (Rituxan)
- Filgrastim (Neupogen) 5 µg/kg SC once per day on days 7 to 14 (10 µg/kg with cycle 3, given until collection of peripheral blood stem cells)
References
- Zelenetz AD, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz CH. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003;14 Suppl 1:i5-10. link to original article contains verified protocol PubMed
- Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A, O'Connor O, Filippa DA, Teruya-Feldstein J, Gencarelli A, Qin J, Waxman A, Yahalom J, Moskowitz CH. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004 May 15;103(10):3684-8. Epub 2004 Jan 22. link to original article contains regimen PubMed
- Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol PubMed
- Guo Y, Chen Y, Hong X, Yu L, Ma J, Shi Y, Liu T, Jiang W, Zhu J, Jin J, Zou P, Wu D, Shen Z. [A phase II multicenter study to investigate R-ICE as a salvage therapy for relapsed diffuse large B-cell lymphoma]. Zhonghua Xue Ye Xue Za Zhi. 2014 Apr;35(4):314-7. Chinese. link to original article PubMed
RICER
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RICER: Rituximab, Ifosfamide, Carboplatin, Etoposide, Revlimid (Lenalidomide)
Regimen
Study | Evidence |
Feldman et al. 2014 | Phase II |
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with Mesna (Mesnex)
- Carboplatin (Paraplatin) AUC 5 (maximum dose of 800 mg per cycle) IV once on day 2
- Etoposide (Vepesid) 100 mg/m2 IV bolus once per day on days 2 to 4
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 7
Supportive medications:
- Mesna (Mesnex) 5,000 mg/m2 IV continuous infusion over 24 hours on day 2, mixed together with Ifosfamide (Ifex)
- Aspirin 81 mg PO once per day from day 1 until platelets < 50,000
- Low dose LMWH for patients intolerant of Aspirin
- " Granulocyte colony-stimulating factor was administered after R-ICE"
14-day cycle x 2 cycles
Responders received a 3rd cycle with stem cell collection 10 to 14 days afterwards, followed by autologous stem cell transplant.
References
- Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. link to original article contains verified protocol PubMed
R-IFE
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R-IFE: Rituximab, IFosfamide, Etoposide
Regimen
Study | Evidence |
Pardal et al. 2014 | Phase II |
Treatment preceded by R-MegaCHOP x3; these were patients with PET-positive disease at interim assessment.
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Ifosfamide (Ifex) 10,000 mg/m2 IV continuous infusion over 72 hours on days 1 to 3
- Etoposide (Vepesid) 150 mg/m2 IV over 12 hours once per day on days 1 to 3
Supportive medications:
- Mesna (Mesnex) given after R-IFE; details not supplied in manuscript
- Pegfilgrastim (Neulasta) given after each cycle
2 cycles (duration not specified)
Responders proceeded to undergo autologous stem cell transplant.
References
- Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. link to original article contains verified protocol PubMed
R-NIMP
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R-NIMP: Rituximab, Navelbine (Vinorelbine), Ifosfamide, Mitoxantrone, Prednisone
Regimen
Study | Evidence |
Gyan et al. 2013 | Phase II |
BSA was capped at 2 for all dose calculations.
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 15
- Ifosfamide (Ifex) 1,000 mg/m2 IV continuous infusion from day 1 to 5 (total dose 5,000 mg/m2)
- Mitoxantrone (Novantrone) 10 mg/m2 IV once on day 1
- Prednisone (Sterapred) 1 mg/kg (route not specified) once per day on days 1 to 5
Supportive medications:
- Mesna (Mesnex) given with Ifosfamide (Ifex) "at the same dose"; schedule not specified in the paper
- Pegfilgrastim (Neulasta) 6 mg SC once on day 7 was recommended
- Epoietin alpha support was recommended for Hgb < 10 g/dL
28-day cycle x 3 cycles
Responders were recommended to undergo 3 additional cycles or autologous stem cell transplant.
References
- Gyan E, Damotte D, Courby S, Sénécal D, Quittet P, Schmidt-Tanguy A, Banos A, Le Gouill S, Lamy T, Fontan J, Maisonneuve H, Alexis M, Dreyfus F, Tournilhac O, Laribi K, Solal-Céligny P, Arakelyan N, Cartron G, Gressin R; GOELAMS Group. High response rate and acceptable toxicity of a combination of rituximab, vinorelbine, ifosfamide, mitoxantrone and prednisone for the treatment of diffuse large B-cell lymphoma in first relapse: results of the R-NIMP GOELAMS study. Br J Haematol. 2013 Jul;162(2):240-9. Epub 2013 May 21. link to original article contains verified protocol PubMed
Temsirolimus (Torisel)
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Regimen
Study | Evidence |
Smith et al. 2010 | Phase II |
- Temsirolimus (Torisel) 25 mg IV over 30 minutes once per week
28-day cycles x up to 6 cycles
References
- Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. Epub 2010 Sep 13. link to original article contains verified protocol PubMed
TTR
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TTR: Taxol (paclitaxel), Topotecan, Rituximab
Regimen
Study | Evidence |
Westin et al. 2014 | Phase II |
- Paclitaxel (Taxol) 200 mg/m2 IV once on day 2
- Topotecan (Hycamtin) 1 mg/m2 IV once per day on days 2 to 6
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Supportive medications:
- Filgrastim (Neupogen) 5 µg/kg SC once per day from day 7 until neutrophil recovery
- Dexamethasone (Decadron) 20 mg IV once 30 minutes prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 50 mg IV once 30 minutes prior to Paclitaxel (Taxol)
21-day cycle up to a maximum of 6 cycles
References
- Westin JR, McLaughlin P, Romaguera J, Hagemeister FB, Pro B, Dang NH, Samaniego F, Rodriguez MA, Fayad L, Oki Y, Fanale M, Fowler N, Nastoupil L, Feng L, Loyer E, Younes A. Paclitaxel, topotecan and rituximab: long term outcomes of an effective salvage programme for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2014 Oct;167(2):177-84. Epub 2014 Jul 8. link to original article contains verified protocol PubMed
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Regimen
Study | Evidence | Comparator | |
Balzarotti et al. 1996 | Non-randomized, <20 patients in this subgroup | ||
Pettengell et al. 2012 | Phase III, <20 in this arm | Pixantrone |
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1, 8, 15, 22
28-day cycles
References
- Balzarotti M, Santoro A, Tondini C, Fornier M, Bonadonna G. Activity of single agent vinorelbine in pretreated non-Hodgkin's lymphoma. Ann Oncol. 1996 Nov;7(9):970-2. link to original article contains verified protocol PubMed
- Review: Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82. Review. link to original article PubMed
- Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. link to original article contains verified protocol PubMed
Consolidation and/or maintenance after salvage therapy
Autologous stem cell transplant
Regimen #1
Study | Evidence | Comparator | Efficacy |
Philip et al. 1995 (PARMA) | Phase III | DHAP x4 | Increased OS |
Treatment preceded by DHAP x 2. Radiation was also given to sites of bulky disease (>5cm); see paper for details.
- BEAC followed by autologous stem cell transplant
Follow the link for details.
Regimen #2
Study | Evidence | ||
Gisselbrecht et al. 2010 (CORAL) | Non-randomized | ||
Pardal et al. 2014 | Phase II |
Treatment in CORAL preceded by R-ICE x 3 versus R-DHAP x 3. Treatment in Pardal et al. 2014 preceded by R-MegaCHOP x3 and R-IFE x 2.
- BEAM followed by autologous stem cell transplant
Follow the link for details. In CORAL, treatment was followed by maintenance rituximab versus observation.
Regimen #3
Study | Evidence |
Feldman et al. 2014 | Phase II |
Treatment preceded by RICER x 3.
- BEAM followed by autologous stem cell transplant
Follow the link for details. If patients were fully recovered within 90 days, they proceeded to lenalidomide maintenance.
Regimen #4
Study | Evidence |
Kirschey et al. 2014 | Phase II |
Treatment preceded by R-DexaBEAM x 2.
References
- Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. 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 PubMed
- Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. link to original article contains verified protocol PubMed
- Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. link to original article contains verified protocol PubMed
- Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. link to original article contains verified protocol PubMed
- Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized Comparison of Gemcitabine, Dexamethasone, and Cisplatin Versus Dexamethasone, Cytarabine, and Cisplatin Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed and Refractory Aggressive Lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. link to original article contains verified protocol PubMed
- Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. link to original article contains verified protocol PubMed
Lenalidomide (Revlimid)
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Regimen
Study | Evidence |
Feldman et al. 2014 | Phase II |
Treatment preceded by BEAM autologous transplant.
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
28-day cycles for up to 12 months
References
- Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. link to original article contains verified protocol PubMed
Observation
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Regimen
Study | Evidence | Comparator | Efficacy |
Gisselbrecht et al. 2012 (CORAL) | Phase III | Rituximab | Seems not superior |
No further treatment after BEAM autologous stem cell transplant.
References
- Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Dührsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Brière J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. Epub 2012 Oct 22. link to original article contains verified protocol PubMed
Rituximab (Rituxan)
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Regimen
Study | Evidence | Comparator | Efficacy |
Gisselbrecht et al. 2012 (CORAL) | Phase III | Observation | Seems not superior |
Treatment preceded by BEAM autologous stem cell transplant, and begins on day +28.
- Rituximab (Rituxan) 375 mg/m2 IV once every 8 weeks
1 year course
References
- Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Dührsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Brière J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. Epub 2012 Oct 22. link to original article contains verified protocol PubMed
Response criteria
NCI Sponsored International Working Group Criteria (1999)
- Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. link to original article PubMed
Investigational agents
These are drugs under study with at least some promising results for this disease.