Aggressive Non-Hodgkin lymphoma

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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

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

Supportive medications:

14-day cycles x 2 cycles, beginning 4 weeks after completion of induction, then

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

14-day cycles x 2 cycles, beginning 2 weeks after completion of REI

References

  1. 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

21-day cycles x 8 cycles

Regimen #2, Pfreundschuh, et al. 2004 & Verdonck, et al. 2007

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

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

21-day cycles x 8 cycles

Supportive medications:

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

References

  1. 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
  2. Jones SE, Grozea PN, Metz EN, Haut A, Stephens RL, Morrison FS, Butler JJ, Byrne GE Jr, Moon TE, Fisher R, Haskins CL, Coltman CA Jr. 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
  3. 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
  4. 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
  5. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. link to original article contains verified protocol PubMed
  6. 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
  7. 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
  8. 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
  9. 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

14-day cycles x up to 6 cycles

Supportive medications:

Regimen #2, Verdonck, et al. 2007 - I-CHOP

Level of Evidence: Phase III Equivalent OS Increased toxicity

14-day cycles x 6 cycles

Supportive medications:

Regimen #3, Pfreundschuh, et al. 2004 - CHOP-14

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

  1. Blayney DW, LeBlanc ML, Grogan T, Gaynor ER, Chapman RA, Spiridonidis CH, Taylor SA, Bearman SI, Miller TP, Fisher RI; Southwest Oncology Group. Dose-intense chemotherapy every 2 weeks with dose-intense cyclophosphamide, doxorubicin, vincristine, and prednisone may improve survival in intermediate- and high-grade lymphoma: a phase II study of the Southwest Oncology Group (SWOG 9349). J Clin Oncol. 2003 Jul 1;21(13):2466-73. link to original article contains verified protocol PubMed
  2. Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. link to original article contains verified protocol PubMed
  3. 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

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

  1. 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

CODOX-M/IVAC

CODOX-M: Cyclophosphamide, Oncovin, DOXorubicin, M ethotrexate

IVAC: Ifosfamide, Vepesid (etoposide), AC Ara-C (cytarabine)

Part 1: CODOX-M

Age 65 years or younger:

Age more than 65 years:

  • Folinic acid (Leucovorin) 15 mg/m2 IV Q3H, starting 36 hours after start of IV methotrexate until 48 hours, then Q6H until methotrexate level undetectable

Supportive medications:

Part 2: IVAC

Age 65 years or younger:

Age more than 65 years:

Supportive medications:

References

  1. Mead GM, Barrans SL, Qian W, Walewski J, Radford JA, Wolf M, Clawson SM, Stenning SP, Yule CL, Jack AS; UK National Cancer Research Institute Lymphoma Clinical Studies Group; Australasian Leukaemia and Lymphoma Group. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial). Blood. 2008 Sep 15;112(6):2248-60. doi: 10.1182/blood-2008-03-145128. Epub 2008 Jul 8. 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

Supportive medications:

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

Supportive medications:

21-day cycles x 6-8 cycles

References

  1. 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
  2. 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

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

  1. 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
  2. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. link to original article PubMed

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

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:

References

  1. 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
  2. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. link to original article PubMed

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

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

21-day cycles x 6 cycles

Supportive medications:

References

  1. 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
  2. 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
  3. Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. link to original article contains verified protocol PubMed
  4. 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
  5. 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
  6. 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

7-day course, then

Main regimen

14-day cycles x 6-8 cycles (8 doses of rituximab regardless of total # of cycles)

Supportive medications:

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

  1. 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

21-day cycles x up to 8 cycles

References

See references for CVP

R-EPOCH

R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin

Synonyms: EPOCH-R, REPOCH

Structured Concept: C63461 (NCI-T), C1882521 (NCI-MT/UMLS)

Regimen

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:
  • 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

  1. Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, Steinberg SM, Little RF, Janik J, Gutierrez M, Raffeld M, Staudt L, Cheson BD, Longo DL, Harris N, Jaffe ES, Chabner BA, Wittes R, Balis F. Dose-adjusted EPOCH chemotherapy for untreated large B-cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002 Apr 15;99(8):2685-93. link to original article contains verified protocol PubMed
  2. 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
  3. 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
  4. 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
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