Non-Hodgkin lymphoma
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Follicular lymphoma
BR
BR: Bendamustine, Rituximab
Regimen #1, Rummel, et al. 2005
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
Cycle 1 is started 7 days after the first dose of rituximab
- Bendamustine (Treanda) 90 mg/m2 IV over 30 minutes on days 1 & 2 of cycles 1-4
- Rituximab (Rituxan) 375 mg/m2 IV on day 1 of cycles 1-5
28-day cycles x 5 cycles
Regimen #2, Rummel, et al. 2012 - StiL NHL1
- Bendamustine (Treanda) 90 mg/m2 IV on days 1 & 2
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
28-day cycles x up to 6 cycles
References
- Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A, Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol. 2005 May 20;23(15):3383-9. link to original article contains protocol PubMed
- Mathias J. Rummel, Norbert Niederle, Georg Maschmeyer, Andre G. Banat, Ulrich von Gruenhagen, Christoph Losem, Dorothea Kofahl-Krause, Gerhard Heil, Manfred Welslau, Christina Balser, Ulrich Kaiser, Eckhart Weidmann, Heinz A. Duerk, Harald Ballo, Martina Stauch, Juergen Barth, Axel Hinke, Wolfram Brugger, Study Group Indolent Lymphomas (StiL). Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL): Updated results from the StiL NHL1 study. 2012 ASCO Annual Meeting abstract 3. link to abstract ASCO Post article ASCO plenary session video
BVR
BVR: Bendamustine, Velcade, Rituximab
Regimen #1, Friedberg, et al. 2011
- Bendamustine (Treanda) 90 mg/m2 IV over 30-60 minutes on days 1 & 4, given last
- Bortezomib (Velcade) 1.3 mg/m2 IV push on days 1, 4, 8, 11, given first
- Rituximab (Rituxan) 375 mg/m2 IV on day 1, given after bortezomib and before bendamustine
28-day cycles x 6 cycles
Supportive medications:
- Premedications, antiemetic therapy, and growth factor support per institutional guidelines
- No routine antibiotic or antiviral prophylaxis was given
Regimen #2, Fowler, et al. 2011
- Bendamustine (Treanda) 50-90 mg/m2 IV over 60 minutes on days 1 & 2, given after bortezomib and before rituximab
- Bortezomib (Velcade) 1.6 mg/m2 IV on days 1, 8, 15, 22, given first
- Rituximab (Rituxan) 375 mg/m2 IV on days 1, 8, 15, 22 of cycle 1, then 375 mg/m2 IV on day 1 of cycles 2-5; given last
35-day cycles x 5 cycles
Supportive medications:
- Antiviral prophylaxis at physician discretion
References
- Friedberg JW, Vose JM, Kelly JL, Young F, Bernstein SH, Peterson D, Rich L, Blumel S, Proia NK, Liesveld J, Fisher RI, Armitage JO, Grant S, Leonard JP. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Blood. 2011 Mar 10;117(10):2807-12. Epub 2011 Jan 14. link to original article contains protocol PubMed
- Fowler N, Kahl BS, Lee P, Matous JV, Cashen AF, Jacobs SA, Letzer J, Amin B, Williams ME, Smith S, Saleh A, Rosen P, Shi H, Parasuraman S, Cheson BD. Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. J Clin Oncol. 2011 Sep 1;29(25):3389-95. Epub 2011 Aug 1. link to original article contains protocol PubMed
CVP
CVP: Cyclophosphamide, Vincristine, Prednisone
Synonyms: COP, COP protocol 2, VCP
Structured Concept: C9573 (NCI-T), C0056633 (NCI-MT/UMLS)
Regimen
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
- Prednisone (Sterapred) 40 mg/m2 PO on days 1-5
21-day cycles x up to 8 cycles
References
- Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. link to original article contains protocol PubMed
Cyclophosphamide (Cytoxan)
Regimen
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO daily, with dose modifications according to WBC and platelet count as listed in table 1 of Peterson, et al. 2003
References
- Peterson BA, Petroni GR, Frizzera G, Barcos M, Bloomfield CD, Nissen NI, Hurd DD, Henderson ES, Sartiano GP, Johnson JL, Holland JF, Gottlieb AJ. Prolonged single-agent versus combination chemotherapy in indolent follicular lymphomas: a study of the cancer and leukemia group B. J Clin Oncol. 2003 Jan 1;21(1):5-15. link to original article contains protocol PubMed
CHOP -> Tositumomab & I-131 (Bexxar)
CHOP: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
Regimen
CHOP
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
- Prednisone (Sterapred) 100 mg PO on days 1-5
21-day cycles x 6 cycles
Supportive medications:
- Allopurinol (Aloprim) 300 mg PO daily for patients with bulky disease
Tositumomab & I-131 (Bexxar) dosimetric step
- On Day 0, infusions of:
- Tositumomab 450 mg IV over 1 hour
- Tositumomab 35 mg labeled with 5 mCi of Iodine-131 IV over 20 minutes
- First scan of whole body dosimetry & redistribution
- Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
- Day 6 or 7: Third scan of whole body dosimetry & redistribution
Tositumomab & I-131 (Bexxar) therapeutic step
- Any day from day 7-14, infusions of:
- Tositumomab 450 mg IV over 1 hour
- Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body IV over 20 minutes
- 65 cGy total body dose used for patients with platelet counts of 100-150,000/mm3
Calculated dose of I-131 is based on information from serial total-body gamma-camera counts
Supportive medications:
- Acetaminophen (Tylenol) 650 mg PO as premedication for tositumomab
- Diphenhydramine (Benadryl) 50 mg PO as premedication for tositumomab
- Potassium iodide 4 drops PO TID, Lugol solution 20 drops PO TID, or potassium iodide tablets 130 mg PO daily starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion
References
- Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, LeBlanc M, Gaynor ER, Rivkin SE, Fisher RI. A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin lymphoma: Southwest Oncology Group Protocol S9911. Blood. 2003 Sep 1;102(5):1606-12. Epub 2003 May 8. link to original article contains protocol PubMed
- Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, Leblanc M, Fisher RI; Southwest Oncology Group. Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin's lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol. 2006 Sep 1;24(25):4143-9. Epub 2006 Aug 8. link to original article PubMed
FCMR
FCMR: Fludarabine, Cyclophosphamide, Mitoxantrone, Rituximab
Regimen
- Fludarabine (Fludara) 25 mg/m2 IV over 30 minutes on days 1-3
- Cyclophosphamide (Cytoxan) 200 mg/m2 IV over 4 hours on days 1-3
- Mitoxantrone (Novantrone) 8 mg/m2 IV over 30 minutes on day 1
- Rituximab (Rituxan) 375 mg/m2 IV on day 0
28-day cycles x 4 cycles
References
- Forstpointner R, Dreyling M, Repp R, Hermann S, Hänel A, Metzner B, Pott C, Hartmann F, Rothmann F, Rohrberg R, Böck HP, Wandt H, Unterhalt M, Hiddemann W; German Low-Grade Lymphoma Study Group. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004 Nov 15;104(10):3064-71. Epub 2004 Jul 29. link to original article contains protocol PubMed
Fludarabine (Fludara) & Rituximab (Rituxan)
Regimen
- Rituximab (Rituxan) 375 mg/m2 IV on days 1 & 4
Cycle 1 begins 72 hours after the second dose of rituximab
- Fludarabine (Fludara) 25 mg/m2 IV on days 1-5 of cycles 1-6
- Rituximab (Rituxan) 375 mg/m2 IV given 72 hours before cycle 2 day 1, 72 hours before cycle 4 day 1, and 72 hours before cycle 6 day 1
- Rituximab (Rituxan) 375 mg/m2 IV on days 1 & 4 of cycle 7
28-day cycles x 7 cycles
References
- Czuczman MS, Koryzna A, Mohr A, Stewart C, Donohue K, Blumenson L, Bernstein ZP, McCarthy P, Alam A, Hernandez-Ilizaliturri F, Skipper M, Brown K, Chanan-Khan A, Klippenstein D, Loud P, Rock MK, Benyunes M, Grillo-Lopez A, Bernstein SH. Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma. J Clin Oncol. 2005 Feb 1;23(4):694-704. link to original article contains protocol PubMed
Rituximab (Rituxan), Ibritumomab tiuxetan & Yttrium-90 (Zevalin)
Regimen #1, Morschhauser, et al. 2008
Consolidation therapy for patients in complete or partial remission after first-line therapy
- Rituximab (Rituxan) 250 mg/m2 IV on days 1 & 8
- Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 14.8 MBq/kg (maximum dose of 1184 MBq) IV slow push over 10 minutes on day 8 immediately following rituximab
8-day course of therapy
Regimen #2, Witzig, et al. Aug 2002
For patients with rituximab-refractory disease
- Rituximab (Rituxan) 250 mg/m2 IV on days 1 & 8
- Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes on day 8 immediately following rituximab
8-day course of therapy
Regimen #3, Witzig, et al. May 2002
For patients with relapsed or refractory disease
- Rituximab (Rituxan) 250 mg/m2 IV on days 1 & 8
- Ibritumomab tiuxetan 1.6 mg & Indium-111 5 mCi IV over 10 minutes on day 1
- Ibritumomab tiuxetan & Yttrium-90 (Zevalin) 0.4 mCi/kg (15 MBq/kg) (maximum dose of 32 mCi/1.2 GBq) IV over 10 minutes on day 8 immediately following rituximab
8-day course of therapy
References
- Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-López AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. link to original article contains protocol PubMed
- Witzig TE, Flinn IW, Gordon LI, Emmanouilides C, Czuczman MS, Saleh MN, Cripe L, Wiseman G, Olejnik T, Multani PS, White CA. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. J Clin Oncol. 2002 Aug 1;20(15):3262-9. link to original article contains protocol PubMed
- Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, Huijgens PC, Kolstad A, d'Amore F, Gonzalez Diaz M, Petrini M, Sebban C, Zinzani PL, van Oers MH, van Putten W, Bischof-Delaloye A, Rohatiner A, Salles G, Kuhlmann J, Hagenbeek A. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5156-64. Epub 2008 Oct 14. link to original article contains protocol PubMed
R-CHOP
R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
Regimen #1, Hiddemann, et al. 2005
Level of Evidence: Phase III Improved OS Increased toxicity
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
- Prednisone (Sterapred) 100 mg/m2 PO on days 1-5
- Rituximab (Rituxan) 375 mg/m2 IV on day 0
21-day cycles x 6-8 cycles
Regimen #2, Czuczman, et al. 1999 & 2004
Level of Evidence: Phase II
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
- Prednisone (Sterapred) 100 mg/m2 PO on days 1-5
- Rituximab (Rituxan) doses given by the following schedule:
- Rituximab (Rituxan) 375 mg/m2 IV on days -6 & -1 of cycle 1 (7 and 2 days before cycle 1 day 1)
- Rituximab (Rituxan) 375 mg/m2 IV 2 days before cycle 3 day 1; and 2 days before cycle 5 day 1
- Rituximab (Rituxan) 375 mg/m2 IV 8 days and 15 days after completion of cycle 6 (i.e. what would be cycle 7 days 8 & 15)
21-day cycles x 6 cycles
References
- Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan;17(1):268-76. link to original article contains protocol PubMed
- Czuczman MS, Weaver R, Alkuzweny B, Berlfein J, Grillo-López AJ. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin's lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol. 2004 Dec 1;22(23):4711-6. Epub 2004 Oct 13. link to original article PubMed
- Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, Reiser M, Metzner B, Harder H, Hegewisch-Becker S, Fischer T, Kropff M, Reis HE, Freund M, Wörmann B, Fuchs R, Planker M, Schimke J, Eimermacher H, Trümper L, Aldaoud A, Parwaresch R, Unterhalt M. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005 Dec 1;106(12):3725-32. Epub 2005 Aug 25. link to original article contains protocol PubMed
R-CVP
R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone
Level of Evidence: Phase III Improved OS Similar toxicity
Regimen
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
- Prednisone (Sterapred) 40 mg/m2 PO on days 1-5
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
21-day cycles x up to 8 cycles
References
- Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, Solal-Celigny P, Offner F, Walewski J, Raposo J, Jack A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005 Feb 15;105(4):1417-23. link to original article contains protocol PubMed
- Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, Offner FC, Gomez-Codina J, Belch A, Cunningham D, Wassner-Fritsch E, Stein G. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008 Oct 1;26(28):4579-86. Epub 2008 Jul 28. link to original article PubMed
R-FND
R-FND: Rituximab, Fludarabine, Novantrone, Dexamethasone
Regimen
Primary reference was not able to be obtained to verify this regimen
- Fludarabine (Fludara) 25 mg/m2 IV on days 1-3
- Mitoxantrone (Novantrone) 10 mg/m2 IV on day 1
- Dexamethasone (Decadron) 20 mg PO/IV on days 1-5
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
28-day cycles x up to 8 cycles
Supportive medications:
- Prophylactic trimethoprim/sulfamethoxazole, acyclovir (Zovirax), and fluconazole
References
- McLaughlin P, Hagemeister FB, Rodriguez MA, Sarris AH, Pate O, Younes A, Lee MS, Dang NH, Romaguera JE, Preti AH, McAda N, Cabanillas F. Safety of fludarabine, mitoxantrone, and dexamethasone combined with rituximab in the treatment of stage IV indolent lymphoma. Semin Oncol. 2000 Dec;27(6 Suppl 12):37-41. PubMed
- P. McLaughlin, M. A. Rodriguez, F. B. Hagemeister, J. Romaguera, A. H. Sarris, A. Younes, N. H. Dang, A. Goy, F. Samaniego, M. Hess, et al. Stage IV indolent lymphoma: A randomized study of concurrent vs. sequential use of FND chemotherapy (fludarabine, mitoxantrone, dexamethasone) and rituximab (R) monoclonal antibody therapy, with interferon maintenance. 2003 ASCO Annual Meeting Abstract 2269. link to abstract
- Hagemeister F, Cabanillas F, Coleman M, Gregory SA, Zinzani PL. The role of mitoxantrone in the treatment of indolent lymphomas. Oncologist. 2005 Feb;10(2):150-9. link to original article PubMed
- Liu Q, Fayad L, Cabanillas F, Hagemeister FB, Ayers GD, Hess M, Romaguera J, Rodriguez MA, Tsimberidou AM, Verstovsek S, Younes A, Pro B, Lee MS, Ayala A, McLaughlin P. Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center. J Clin Oncol. 2006 Apr 1;24(10):1582-9. link to original article PubMed
- G. E. Manoukian, F. B. Hagemeister, P. McLaughlin, L. Fayad, F. Samaniego, A. Goy, J. E. Romaguera, B. Pro, F. Cabanillas, M. A. Rodriguez. Rituximab, fludarabine, mitoxantrone, and dexamethasone (R-FND) for patients with relapsed indolent B-cell lymphoma (RIL). 2010 ASCO Annual Meeting Abstract 8078. link to abstract
Rituximab (Rituxan)
Regimen
- Rituximab (Rituxan) 375 mg/m2 IV weekly x 4 weeks; initial infusion rate of 50 mg/H, then increased as tolerated by 50 mg/H every 30 minutes, to a maximum rate of 300 mg/H
4-week course
Supportive medications:
- Acetaminophen (Tylenol) 650 mg PO 30 minutes prior to each dose of rituximab
- Diphenhydramine (Benadryl) 50 mg PO 30 minutes prior to each dose of rituximab
Maintenance regimen (Salles, et al. 2011)
Starts 8 weeks after the last induction treatment
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
8-week cycles x 12 cycles
References
- Colombat P, Salles G, Brousse N, Eftekhari P, Soubeyran P, Delwail V, Deconinck E, Haïoun C, Foussard C, Sebban C, Stamatoullas A, Milpied N, Boué F, Taillan B, Lederlin P, Najman A, Thièblemont C, Montestruc F, Mathieu-Boué A, Benzohra A, Solal-Céligny P. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood. 2001 Jan 1;97(1):101-6. link to original article contains protocol PubMed
- Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7. link to original article contains protocol PubMed
- Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011 Jan 1;377(9759):42-51. Epub 2010 Dec 20. link to original article contains protocol PubMed
Tositumomab & I-131 (Bexxar)
Regimen
Dosimetric step
- On Day 0, infusions of:
- Tositumomab 450 mg IV over 1 hour
- Tositumomab 35 mg labeled with 5 mCi of Iodine-131 IV over 20 minutes
- First scan of whole body dosimetry & redistribution
- Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
- Day 6 or 7: Third scan of whole body dosimetry & redistribution
Therapeutic step
- Any day from day 7-14, infusions of:
- Tositumomab 450 mg IV over 1 hour
- Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body IV over 20 minutes
- 65 cGy total body dose used for patients with platelet counts of 100-150,000/mm3
Calculated dose of I-131 is based on information from serial total-body gamma-camera counts
Supportive medications:
- Acetaminophen (Tylenol) 650 mg PO as premedication for tositumomab
- Diphenhydramine (Benadryl) 50 mg PO as premedication for tositumomab
- Potassium iodide 2 drops PO TID starting at least 24 hours before the dosimetric step and continuing for 14 days after the therapeutic infusion; may also use Lugol’s solution or potassium iodide tablets
References
- Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L, Lister TA, Stagg RJ, Tidmarsh GF, Kroll S, Wahl RL, Knox SJ, Vose JM. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2001 Oct 1;19(19):3918-28. link to original article contains protocol PubMed
- Kaminski MS, Tuck M, Estes J, Kolstad A, Ross CW, Zasadny K, Regan D, Kison P, Fisher S, Kroll S, Wahl RL. 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med. 2005 Feb 3;352(5):441-9. link to original article contains protocol PubMed
- Fisher RI, Kaminski MS, Wahl RL, Knox SJ, Zelenetz AD, Vose JM, Leonard JP, Kroll S, Goldsmith SJ, Coleman M. Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin's lymphomas. J Clin Oncol. 2005 Oct 20;23(30):7565-73. Epub 2005 Sep 26. link to original article PubMed
- Tositumomab and I-131 (Bexxar) package insert
Mantle cell lymphoma
BR
BR: Bendamustine, Rituximab
- Regimen is the same as BR in follicular lymphoma, Regimen #2, Rummel, et al. 2012 - StiL NH1
CALGB 59909
Regimen
Treatments 1-2, R-M-CHOP
- Rituximab (Rituxan) 375 mg/m2 IV on day 1 (rituximab withheld if circulating mantle cells are >10,000 cells/uL)
- Methotrexate (MTX) 300 mg/m2 IV over 4 hours on day 2
- Folinic acid (Leucovorin) 50 mg/m2 IV every 6 hours x 3 doses, starting 24 hours after completion of methotrexate, then 10 mg/m2 IV/PO every 6 hours until serum methotrexate level <0.05 uM
- Cyclophosphamide (Cytoxan) 2000 mg/m2 IV over 2 hours on day 3
- Doxorubicin (Adriamycin) 50 mg/m2 IV on day 3
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg for patients >40 years old) IV on day 3
- Prednisone (Sterapred) 100 mg/m2 PO on days 3-7
Interval between treatment 1 & 2 based on count recovery. Median days between treatment 1 & 2 was 23 days, with a range of 16-41 days observed.
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting on day 4, to continue until ANC >10000 once or >5000 twice
- Levofloxacin (Levaquin) 500 mg PO daily, starting on day 6, to continue until ANC ≥1500
- Fluconazole (Diflucan) 200 mg PO daily, starting on day 6, to continue until ANC ≥1500
Patients with ≤15% involvement by disease in bone marrow biopsy after treatment 2 proceed to treatment 3. If bone marrow biopsy after treatment 2 has >15% involvement by disease, repeat treatment 2 (identified as "treatment 2.5"). Patients with >15% bone marrow involvement by disease after treatment 2.5 were removed from protocol.
Treatment 3, "EAR"
EAR: Etoposide, Ara-C, Rituximab
Treatment 3 begins 4 weeks after treatment 2, if ANC ≥1000, platelets ≥100,000/uL, Cr <2 mg/dL, total bilirubin <2x upper limit of normal, and AST <3x upper limit of normal.
- Etoposide (Vepesid) 10 mg/kg/day (40 mg/kg total dose) IV continuous infusion over 96 hours on days 1-4
- Cytarabine (Cytosar) 2000 mg/m2 IV over 2 hours BID on days 1-4 (8 total doses)
- Rituximab (Rituxan) 375 mg/m2 IV on days 6 & 13
- Daily leukapheresis to start when WBC ≥5000/uL
Supportive medications:
- Filgrastim (Neupogen) 10 mcg/kg SC daily starting on day 14, to continue until peripheral blood stem cell collection is complete
- Levofloxacin (Levaquin) 500 mg PO daily, starting on day 7, to continue until ANC ≥500
- Fluconazole (Diflucan) 200 mg PO daily, starting on day 6, to continue until ANC ≥500
- Acyclovir (Zovirax) 200 mg PO TID, starting on day 6, to continue until 1 year after autologous stem cell transplant (ASCT)
- Note: Text specified that Trimethoprim/Sulfamethoxazole (Bactrim DS) prophylaxis started during treatment 3 (see dose/schedule in treatment 4)--although table 1 did not list it--to continue until 3 months after ASCT.
Treatment 4, "CBV"
CBV: Cyclophosphamide, BiCNU, VP-16
- Carmustine (BiCNU) 15 mg/kg (maximum dose of 550 mg/m2) IV over 1 hour on day -6
- Etoposide (Vepesid) 60 mg/kg IV over 4 hours on day -4
- Cyclophosphamide (Cytoxan) 100 mg/kg IV over 2 hours on day -2
- Autologous blood stem cells infused on day 0.
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily starting on day +4, to continue until ANC >5000 once or >1500 twice
- Levofloxacin (Levaquin) 500 mg PO daily, starting on day +2, to continue until ANC ≥500
- Fluconazole (Diflucan) 200 mg PO daily, starting on day +1, to continue until ANC ≥500
- Acyclovir (Zovirax) 200 mg PO TID, starting on day -2, to continue until 1 year after ASCT
- Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO BID on Saturday and Sunday, to continue until 3 months after ASCT
Treatment 5, Rituximab
- Rituximab (Rituxan) 375 mg/m2 IV weekly x 2 doses, 6 and 7 weeks after ASCT
Additional considerations
If cerebrospinal fluid (CSF) contained disease with CSF WBC ≤5 cells/uL:
- Methotrexate (MTX) 12 mg intrathecal x 10 total doses during treatments 1-3; not given concurrently with intrathecal methotrexate or cytarabine
If CSF contained >5 cells/uL:
- In addition to intrathecal chemotherapy above, patient also received 2 Gy x 12 fractions (total dose 24 Gy) cranial radiation
If any patient appeared to be experiencing carmustine-induced pneumonitis:
- Prednisone (Sterapred) 0.5 mg/kg PO BID x 2 weeks, then tapered over 4 weeks
References
- Damon LE, Johnson JL, Niedzwiecki D, Cheson BD, Hurd DD, Bartlett NL, Lacasce AS, Blum KA, Byrd JC, Kelly M, Stock W, Linker CA, Canellos GP. Immunochemotherapy and autologous stem-cell transplantation for untreated patients with mantle-cell lymphoma: CALGB 59909. J Clin Oncol. 2009 Dec 20;27(36):6101-8. Epub 2009 Nov 16. link to original article contains protocol PubMed
Hyper-CVAD & Rituximab (Rituxan)
CVAD: Cyclophosphamide, Vincristine, Adriamycin, Dexamethasone
Regimen
Part A (cycles 1, 3, 5, 7):
- Cyclophosphamide (Cytoxan) 300 mg/m2 IV over 3 hours Q12H on days 2-4 (6 total doses)
- Mesna (Mesnex) 600 mg/m2/day IV continuous infusion on days 2-4, starting 1 hour before cytoxan and completed 12 hours after the last dose of cytoxan
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV piggyback on day 5, 12 hours after the last dose of cyclophosphamide, and on day 12
- Doxorubicin (Adriamycin) 16.6-16.7 (note: reference had slightly different dosages in the text vs. table 1) mg/m2/day IV continuous infusion over 72 hours on days 5-7
- Dexamethasone (Decadron) 40 mg PO/IV on days 2-5, 12-15
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
- Patients with peripheral blood involvement could have the cycle 1 dose of rituximab delayed or omitted by clinician discretion
21-day cycles, alternating every 21 days with Part B, for a total of 4 cycles of Part A and 4 cycles of Part B
Part B (cycles 2, 4, 6, 8):
- Methotrexate (MTX) 200 mg/m2 IV over 2 hours, then 800 mg/m2 IV over 22 hours on day 2
- Patients with a Cr >1.5 mg/dL received a 50% reduced dose of methotrexate
- Cytarabine (Cytosar) 3000 mg/m2 (1000 mg/m2 for patients >60 years old or with Cr >1.5) IV over 2 hours Q12H on days 3 & 4 (4 total doses)
- Folinic acid (Leucovorin) 50 mg PO x1 12 hours after methotrexate is complete, then 15 mg PO Q6H x 8 doses. If serum methotrexate level at 24 hours is >1 umol/L or at 48 hours is >0.1 umol/L, dose of folinic acid is increased to 100 mg IV Q3H.
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
- Urine alkalinized to pH of 6.8 or more prior to the start of methotrexate and kept within that range until methotrexate is cleared
- Prednisolone 1% ophthalmic solution 2 drops in each eye 4 times per day on days 3-9was started on the day of the start of cytarabine infusion and was continued for 7 days to prevent chemical conjunctivitis.
21-day cycles, alternating every 21 days with Part A, for a total of 4 cycles of Part A and 4 cycles of Part B
Supportive medications (for both Part A and Part B):
All medications given for 10 days, starting 24-36 hours after doxorubicin infusion is complete
- Filgrastim (Neupogen) 5 mcg/kg SC daily
- Valacyclovir (Valtrex) 500 mg PO daily
- Fluconazole (Diflucan) 100 mg PO daily
- Levofloxacin (Levaquin) 500 mg PO daily or Ciprofloxacin (Cipro) (reference did not specify dose/frequency)
- "Erythropoietin was permitted throughout therapy"
References
- Romaguera JE, Fayad L, Rodriguez MA, Broglio KR, Hagemeister FB, Pro B, McLaughlin P, Younes A, Samaniego F, Goy A, Sarris AH, Dang NH, Wang M, Beasley V, Medeiros LJ, Katz RL, Gagneja H, Samuels BI, Smith TL, Cabanillas FF. High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol. 2005 Oct 1;23(28):7013-23. Epub 2005 Sep 6. link to original article contains protocol PubMed
Nordic regimen, maxi-CHOP, HiDAC, Rituximab (Rituxan)
CHOP: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
HiDAC: High Dose Ara-C
Regimen
Protocol originally started rituximab during cycle 4, but the protocol was amended to start it on cycle 2.
Cycle 1 uses maxi-CHOP, cycle 2 uses HiDAC, cycle 3 uses maxi-CHOP, etc.
- Rituximab (Rituxan) 375 mg/m2 IV on day 1 of cycles 2-5, and 375 mg/m2 IV on days 1 & 9 of cycle 6
maxi-CHOP
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 75 mg/m2 IV on day 1
- Vincristine (Oncovin) 2 mg IV on day 1
- Prednisone (Sterapred) 100 mg PO on days 1-5
21-day cycles, alternating with high-dose cytarabine, for a total of 3 cycles of maxi-CHOP and 3 cycles of high-dose cytarabine
HiDAC/HDAC, high-dose Cytarabine (Cytosar)
- Cytarabine (Cytosar) 3000 mg/m2 IV over 3 hours Q12H on days 1 & 2 (4 total doses)
- Patients >60 years old received Cytarabine (Cytosar) 2000 mg/m2 IV over 3 hours Q12H on days 1 & 2 (4 total doses)
21-day cycles, alternating with maxi-CHOP, for a total of 3 cycles of maxi-CHOP and 3 cycles of high-dose cytarabine
Supportive medications:
- Filgrastim (Neupogen) given during cycle 6 as part of stem cell mobilization, with at least 2 million CD34+ cells/kg harvested
High-dose chemotherapy with BEAM or BEAC started 1-2 weeks after completion of cycle 6, followed by stem cell transplant. If transplant was delayed, an additional 1-2 cycles of chemotherapy with maxi-CHOP or HiDAC could be given.
References
- Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordström M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundström C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. Epub 2008 Jul 14. link to original article PubMed
Marginal zone lymphoma (including MALT lymphomas)
Bortezomib monotherapy
Regimen
- Bortezomib (Velcade) 1.3 mg/m2 IV on days 1, 4, 8, 11
21-day cycles x up to 6 cycles
Supportive medications:
- No routine growth factors, antibiotic, or antiviral prophylaxis was given
References
- Conconi A, Martinelli G, Lopez-Guillermo A, Zinzani PL, Ferreri AJ, Rigacci L, Devizzi L, Vitolo U, Luminari S, Cavalli F, Zucca E; International Extranodal Lymphoma Study Group (IELSG). Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group (IELSG). Ann Oncol. 2011 Mar;22(3):689-95. link to original article contains verified protocol PubMed
Rituximab monotherapy
Level of Evidence: Phase II
Regimen
- Rituximab (Rituxan) 375 mg/m2 IV on days 1, 8, 15, 21
References
- Conconi A, Martinelli G, Thiéblemont C, Ferreri AJ, Devizzi L, Peccatori F, Ponzoni M, Pedrinis E, Dell'Oro S, Pruneri G, Filipazzi V, Dietrich PY, Gianni AM, Coiffier B, Cavalli F, Zucca E. Clinical activity of rituximab in extranodal marginal zone B-cell lymphoma of MALT type. Blood. 2003 Oct 15;102(8):2741-5. link to orginal article contains protocol PubMed
- Martinelli G, Laszlo D, Ferreri AJ, Pruneri G, Ponzoni M, Conconi A, Crosta C, Pedrinis E, Bertoni F, Calabrese L, Zucca E. Clinical activity of rituximab in gastric marginal zone non-Hodgkin's lymphoma resistant to or not eligible for anti-Helicobacter pylori therapy. J Clin Oncol. 2005 Mar 20;23(9):1979-83. link to original article contains protocol PubMed
Aggressive lymphoma (primarily diffuse large B-cell lymphoma)
ACVBP-R
ACVBP-R: Adriamycin, Cyclophosphamide, Vindesine, Bleomycin, Prednisone, Rituximab
Synonyms: R-ACVBP
Structured Concept: none
Level of Evidence: Phase III Improved OS Increased toxicity
Induction Regimen
- Cyclophosphamide (Cytoxan) 1200 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 75 mg/m2 IV on day 1
- Vindesine (Eldisine) 2 mg/m2 IV on days 1 & 5
- Bleomycin (Blenoxane) 10 units IV on days 1 & 5
- Prednisone (Sterapred) 60 mg/m2 PO on days 1-5
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
- Methotrexate (MTX) 15 mg intrathecal on day 1 for CNS prophylaxis
14-day cycles x 4 cycles
Supportive medications:
- Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC daily on days 6-13
Consolidation Regimen
- Methotrexate (MTX) 3000 mg/m2 IV on day 1
Supportive medications:
14-day cycles x 2 cycles, beginning 4 weeks after completion of induction, then
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
- Etoposide (Vepesid) 300 mg/m2 IV on day 1
- Ifosfamide (Ifex) 1500 mg/m2 IV on day 1
14-day cycles x 4 cycles, beginning 2 weeks after completion of MTX, then
- Cytarabine (Cytosar) 100 mg/m2 SC on days 1-4
14-day cycles 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
CHOP
CHOP: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
Synonyms: CHOP-21, ACOP, CAVP, COPA, VACP, VCAP
Structured Concept: C9549 (NCI-T), C0055598 (NCI-MT/UMLS)
Regimen #1, Elias, et al. 1978; Jones, et al. 1979; Fisher, et al. 1993; Miller, et al. 1998
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV bolus over 1-2 minutes on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV bolus over 1-2 minutes on day 1
- Prednisone (Sterapred) 100 mg PO on days 1-5
21-day cycles x 8 cycles
Regimen #2, Pfreundschuh, et al. 2004 & Verdonck, et al. 2007
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
- Vincristine (Oncovin) 2 mg IV on day 1
- Prednisone (Sterapred) 100 mg PO on days 1-5
21-day cycles x 6 cycles
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 daily on days 4-13
Regimen #3, Miller, et al. 1998 - CHOP-21 & radiation
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV bolus over 1-2 minutes on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV bolus over 1-2 minutes on day 1
- Prednisone (Sterapred) 100 mg PO on days 1-5
21-day cycles 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, Coiffier, et al. 2002 & 2010, Feugier, et al. 2005 - LNH-98.5
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
- Prednisone (Sterapred) 40 mg/m2 PO on days 1-5
21-day cycles x 8 cycles
Supportive medications:
- Filgrastim (Neupogen) used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
References
- 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. contains verified protocol PubMed
- Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Butler JJ, Byrne GE Jr, Moon TE, Fisher R, Haskins CL, Coltman CA Jr. Superiority of adriamycin-containing combination chemotherapy in the treatment of diffuse lymphoma: a Southwest Oncology Group study. Cancer. 1979 Feb;43(2):417-25. contains verified protocol PubMed
- 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
- 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
- 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
- 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
- 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
- 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
CHOP Intensified
CHOP-DI: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone, Dose Intense
I-CHOP: Intensified Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
Synonyms: CHOP-14, CHOP-DI, I-CHOP
Structured Concept: none
Regimen #1, Blayney, et al. 2003 - CHOP-DI, SWOG 9349
- Cyclophosphamide (Cytoxan) 1600 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 65 mg/m2 IV on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV on day 1
- Prednisone (Sterapred) 100 mg PO on days 1-5
14-day cycles x up to 6 cycles
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily on days 2-11, or until ANC is greater than 10,000
Regimen #2, Verdonck, et al. 2007 - I-CHOP
Level of Evidence: Phase III Equivalent OS Increased toxicity
- Cyclophosphamide (Cytoxan) 1000 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 70 mg/m2 IV on day 1
- Vincristine (Oncovin) 2 mg IV on day 1
- Prednisone (Sterapred) 100 mg PO on days 1-5
14-day cycles x 6 cycles
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SC daily on days 2-11
Regimen #3, Pfreundschuh, et al. 2004 - CHOP-14
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
- Vincristine (Oncovin) 2 mg IV on day 1
- Prednisone (Sterapred) 100 mg PO on days 1-5
14-day cycles x 6 cycles
Supportive medications:
- Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC daily on days 4-13
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
- 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
CHOPE
CHOPE: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone, Etoposide
Synonyms: CHOEP, VAC0P
Structured Concept: C9702 (NCI-T), C0212922(NCI-MT/UMLS)
Regimen
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
- Vincristine (Oncovin) 2 mg IV on day 1
- Prednisone (Sterapred) 100 mg PO on days 1-5
- Etoposide (Vepesid) 100 mg/m2 IV on days days 1-3
- Patients with initial bulky disease (mass conglomerate at least 7.5 cm) received 36 Gy radiation therapy and to extranodal sites of disease when possible
14 or 21-day cycles x 6 cycles, next cycle to start as long as WBC is >2.5 and platelets >80
- CHOEP-14 uses 14-day cycles; CHOEP-21 uses 21-day cycles
Supportive medications:
- For 14-day cycles: Filgrastim (Neupogen) 300 mcg (for patients <75 kg) or 480 mcg (for patients at least 75 kg) SC daily on days 4-13
- Filgrastim (Neupogen) use for 21-day cycles is by discretion of ordering physician
References
- 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
EPOCH
EPOCH: Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin
Synonyms: CHEOP, DA-EPOCH
Structured Concept: C63779 (NCI-T), C1880475 (NCI-MT/UMLS)
Regimen #1, dose-adjusted EPOCH (DA-EPOCH), Wilson, et al. 2002
- Etoposide (Vepesid) 50 mg/m2/day (total dose of 200 mg/m2) IV continuous infusion on days 1-4
- Prednisone (Sterapred) 60 mg/m2 PO BID on days 1-5
- Vincristine (Oncovin) 0.4 mg/m2/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1-4
- Doxorubicin (Adriamycin) 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1-4
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 5
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SQ daily, 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 daily
- Pentamidine (Nebupent) 300 mg nebulized every 28 days
21-day cycles x 6-8 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.
Regimen #2, original EPOCH protocol, Wilson, et al. 1993
- Etoposide (Vepesid) 50 mg/m2/day (total dose of 200 mg/m2) IV continuous infusion on days 1-4
- Prednisone (Sterapred) 60 mg/m2 PO on days 1-6
- Vincristine (Oncovin) 0.4 mg/m2/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1-4
- Doxorubicin (Adriamycin) 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1-4
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 6
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SQ daily, 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 daily
- Pentamidine (Nebupent) 300 mg nebulized every 28 days
21-day cycles x 6-8 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
- Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. link to original article contains verified protocol PubMed
m-BACOD
m-BACOD: methotrexate (moderate dose), Bleomycin, Adriamycin (doxorubicin), Cyclophosphamide, Oncovin (vincristine), Dexamethasone
Structured Concept: C63458 (NCI-T), C1883662 (NCI-MT/UMLS)
Level of Evidence: Phase II
Regimen
- Methotrexate (MTX) 200 mg/m2 IV on days 8 & 15
- Folinic acid (Leucovorin) 10 mg/m2 PO/IV Q6H x 8 doses, starting 24 hours after methotrexate
- Bleomycin (Blenoxane) 4 units/m2 IV on day 1
- Doxorubicin (Adriamycin) 45 mg/m2 IV on day 1
- Cyclophosphamide (Cytoxan) 600 mg/m2 IV on day 1
- Vincristine (Oncovin) 1 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
- Dexamethasone (Decadron) 6 mg/m2 (no route specified) daily on days 1-5
Dose adjustments:
- If nadir WBC <1,000 or nadir platelets <50,000: 50% of cyclophosphamide and doxorubicin
- If WBC <1,000, platelets <50,000, or creatinine >50% of baseline on day of treatment, methotrexate was omitted
21-day cycles x 10 cycles
Supportive medications: none reported
References
- Shipp MA, Yeap BY, Harrington DP, Klatt MM, Pinkus GS, Jochelson MS, Rosenthal DS, Skarin AT, Canellos GP. The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen. J Clin Oncol. 1990 Jan;8(1):84-93. link to original article contains verified protocol PubMed
- 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
ProMACE-CytaBOM
ProMACE-CytaBOM: Prolix (prednisone), Methotrexate, Adriamycin (doxorubicin), Cyclophosphamide, Etoposide, Cytarabine, Bleomycin, Oncovin (vincristine), Methotrexate
Structured Concept: C63460 (NCI-T), C1882461 (NCI-MT/UMLS)
Regimen
- Cyclophosphamide (Cytoxan) 650 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 25 mg/m2 IV on day 1
- Etoposide (Vepesid) 120 mg/m2 IV on day 1
- Cytarabine (Cytosar) 300 mg/m2 IV on day 8
- Bleomycin (Blenoxane) 5 units/m2 IV on day 8
- Vincristine (Oncovin) 1.4 mg/m2 IV on day 8
- Methotrexate (MTX) 120 mg/m2 IV on day 8
- Folinic acid (Leucovorin) 25 mg/m2 PO Q6H x 4 doses, starting 24 hours after methotrexate
- Prednisone (Prolix) 60 mg/m2 PO daily on days 1-14
- Patients with initial bone or bone marrow involvement who achieved a CR were treated with 2,400 cGy prophylactic cranial irradiation.
Dose adjustments:
- "If WBC is ≥4,000, use 100% doses of all drugs
- If WBC count is 3,000 to 3,999, 100% prednisone, bleomycin, vincristine, cytarabine, and methotrexate; 75% cyclophosphamide, Adriamycin, and etoposide
- If WBC count is 2,000 to 2,999, 100% prednisone, bleomycin, vincristine, and methotrexate; 75% etoposide, cytarabine; 50% cyclophosphamide, Adriamycin
- If WBC count is 1,000 to 1,999, 100% prednisone, bleomycin, vincristine and methotrexate; 25% cyclophosphamide, Adriamycin, etoposide, and cytarabine
- If WBC count is 0 to 999, 100% prednisone, vincristine, and bleomycin; 50% methotrexate, no other drugs
- If platelet count is ≥100,000, use 100% doses of all drugs
- If platelet count is 50,000 to 99,000, 100% prednisone, bleomycin, vincristine, and methotrexate; 50% etoposide and cytarabine; 25% cyclophosphamide and Adriamycin
- If platelet count is 0 to 49,000, 100% prednisone, bleomycin, and vincristine; 50% methotrexate, no other drugs"
21-day cycles x 6 cycles or 2 cycles after maximum clinical response
Supportive medications:
- Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO BID throughout the course of treatment
References
- Longo DL, DeVita VT Jr, Duffey PL, Wesley MN, Ihde DC, Hubbard SM, Gilliom M, Jaffe ES, Cossman J, Fisher RI, et al. Superiority of ProMACE-CytaBOM over ProMACE-MOPP in the treatment of advanced diffuse aggressive lymphoma: results of a prospective randomized trial. J Clin Oncol. 1991 Jan;9(1):25-38. Erratum in: J Clin Oncol 1991 Apr;9(4):710. link to original article contains verified protocol PubMed
- 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
R-CHOP
R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
Synonyms: R-CHOP-21, CHOP-R
Structured Concept: C9760 (NCI-T), C0393023 (NCI-MT/UMLS)
Regimen #1, Coiffier, et al. 2002 & 2010; Feugier, et al. 2005 - LNH-98.5
Level of Evidence: Phase III Mixed OS Similar toxicity
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
- Prednisone (Sterapred) 40 mg/m2 PO on days 1-5
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
21-day cycles x 8 cycles
Supportive medications:
- Filgrastim (Neupogen) used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
Regimen #2, Pfreundschuh, et al. 2006 & 2011 - MInT
Level of Evidence: Phase III Improved OS Similar toxicity
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
- Vincristine (Oncovin) 2 mg IV on day 1
- Prednisone (Sterapred) 100 mg PO on days 1-5
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
- Radiation therapy: 30-40 Gy given to sites of primary bulky disease; 30-40 Gy to primary extranodal disease at physician discretion
21-day cycles x 6 cycles
Supportive medications:
- Filgrastim (Neupogen) or lenograstim used at physician discretion for neutropenia
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
- 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
- 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
- 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
- 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
- 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
R-CHOP Intensified
R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
Synonyms: R-CHOP-14
Structured Concept: none
Regimen
Pre-phase
- Vincristine (Oncovin) 1 mg IV on day 1
- Prednisone (Sterapred) 100 mg PO on days 1-7
7-day course, then
Main regimen
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Doxorubicin (Adriamycin) 50 mg/m2 IV on day 1
- Vincristine (Oncovin) 2 mg IV on day 1
- Prednisone (Sterapred) 100 mg PO on days 1-5
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
14-day cycles x 6-8 cycles (8 doses of rituximab regardless of total # of cycles)
Supportive medications:
- Filgrastim (Neupogen) SC daily starting on day 4, to continue until count recovery
Radiation therapy (only for patients meeting criteria)
- Radiation therapy, 36 Gy to areas of initial bulky disease (masses at least 7.5 cm in diameter) or extranodal involvement
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
R-CVP
R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone
Structured Concept: C63473 (NCI-T), C1882520 (NCI-MT/UMLS)
Regimen
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
- Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2 mg per cycle) IV on day 1
- Prednisone (Sterapred) 40 mg/m2 PO on days 1-5
- Rituximab (Rituxan) 375 mg/m2 IV on day 1
21-day cycles x up to 8 cycles
References
R-EPOCH
R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin
Synonyms: EPOCH-R, REPOCH
Structured Concept: C63461 (NCI-T), C1882521 (NCI-MT/UMLS)
Regimen
- 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 (total dose of 200 mg/m2) IV continuous infusion on days 1-4
- Prednisone (Sterapred) 60 mg/m2 PO BID on days 1-5
- Vincristine (Oncovin) 0.4 mg/m2/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1-4
- Doxorubicin (Adriamycin) 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1-4
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 5
21-day cycles x 6-8 cycles
Supportive medications:
- Filgrastim (Neupogen) 5 mcg/kg SQ daily, 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
- Alternative used only in García-Suárez, et al. 2007: cotrimoxazole 480 mg PO BID 3 days per week
- Atovaquone (Mepron) 1500 mg PO daily
- 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.
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.
21-day cycles x 6-8 cycles
Supportive medications:
- EITHER Filgrastim (Neupogen) 5 mcg/kg SQ daily, starting 24 hours after EPOCH is completed and continuing until "neutrophil recovery"--no absolute count specified
- OR Pegfilgrastim (Neulasta) 6 mg SC x1 24 hours after EPOCH is completed
- Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO 3x per week (e.g. Monday, Wednesday, Friday)
- Fluconazole (Diflucan) 100 mg PO daily
- Ciprofloxacin (Cipro) 500 mg PO BID, starting on day 8 and to continue to at least day 15 or postnadir ANC of at least 1000
- Other fluoroquinolone can be used at discretion of physician
References
- Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. link to original article contains verified protocol PubMed
- 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
HIV-associated lymphoma
R-EPOCH, dose-escalated (EPOCH-R)
Regimen
- Rituximab (Rituxan) 375 mg/m2 IV "before each EPOCH cycle"
- Etoposide (Vepesid) 50 mg/m2/day (total dose of 200 mg/m2) IV continuous infusion on days 1-4
- Prednisone (Sterapred) 60 mg/m2 PO BID on days 1-5
- Vincristine (Oncovin) 0.4 mg/m2/day (total dose of 1.6 mg/m2) IV continuous infusion on days 1-4
- Doxorubicin (Adriamycin) 10 mg/m2/day (total dose of 40 mg/m2) IV continuous infusion on days 1-4
- Cyclophosphamide (Cytoxan) 187 mg/m2 (if CD4 count <100/uL) or 375 mg/m2 (if CD4 count >100/uL) IV over 15 minutes on day 5
- In each subsequent cycle, increase dose of Cyclophosphamide (Cytoxan) by 187 mg/m2 if the neutrophil nadir is >500/μL and platelet nadir is >25/μL. Decrease dose of Cyclophosphamide (Cytoxan) by 187 mg/m2 if the neutrophil nadir is <500/μL or platelet nadir is <25/μL.
21-day cycles x 6-8 cycles
Supportive medications:
- EITHER Filgrastim (Neupogen) 5 mcg/kg SC daily, starting 24 hours after EPOCH is completed and continuing until "neutrophil recovery"—no absolute count specified
- OR Pegfilgrastim (Neulasta) 6 mg SC x1 24 hours after EPOCH is completed
- Trimethoprim/Sulfamethoxazole (Bactrim DS) 160/800 mg PO 3x per week (e.g. Monday, Wednesday, Friday)
- Fluconazole (Diflucan) 100 mg PO daily
- Ciprofloxacin (Cipro) 500 mg PO BID, starting on day 8 and to continue to at least day 15 or postnadir ANC of at least 1000
- Other fluoroquinolone can be used at discretion of physician
References
- Sparano JA, Lee JY, Kaplan LD, Levine AM, Ramos JC, Ambinder RF, Wachsman W, Aboulafia D, Noy A, Henry DH, Von Roenn J, Dezube BJ, Remick SC, Shah MH, Leichman L, Ratner L, Cesarman E, Chadburn A, Mitsuyasu R; AIDS Malignancy Consortium. Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood. 2010 Apr 15;115(15):3008-16. Epub 2009 Dec 18. link to original article contains verified protocol PubMed
CNS lymphoma, including prophylaxis
High-dose Methotrexate (MTX) & Ifosfamide
Regimen
- Methotrexate (MTX) 4000 mg/m2 IV over 4 hours on day 1
- Ifosfamide (Ifex) 1500-2000 mg/m2 IV over 3 hours on days 3-5
- Mesna (Mesnex) for prophylaxis of hemorrhagic cystitis
- Folinic acid (Leucovorin) rescue starting 24 hours after start of methotrexate infusion
- Sodium bicarbonate via IV fluid or PO routes used for urine alkalinization to maintain urine pH of at least 8
- Check methotrexate levels 24, 48, and 72 hours after completion of methotrexate infusion.
Methotrexate (MTX) dose adjusted for creatinine clearances <100 mL/min according to the following formula:
- Dose of methotrexate = (creatinine clearance/100) x 4000 mg/m2; the paper did not specify what method was used for calculating creatinine clearance. Patients with creatinine clearance <50 mL/min were excluded from the study.
up to 8 cycles (reference did not list timing/criteria to be used for next cycle of therapy)
References
- Fischer L, Korfel A, Kiewe P, Neumann M, Jahnke K, Thiel E. Systemic high-dose methotrexate plus ifosfamide is highly effective for central nervous system (CNS) involvement of lymphoma. Ann Hematol. 2009 Feb;88(2):133-9. Epub 2008 Aug 5. link to original article contains verified protocol PubMed