Non-Hodgkin lymphoma

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CHOP

Regimen

Q21days x 6-8 cycles

References

  1. 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

R-CHOP

Regimen

Q21days x 6-8 cycles

References

See references for CHOP

CVP

Regimen

Q21days x up to 8 cycles

References

  1. 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

R-CVP

Regimen

Q21days x up to 8 cycles

References

See references for CVP

EPOCH

Regimen

  • Etoposide (Vepesid) 50 mg/m2/day (200 mg/m2 total) continuous IV infusion days 1-4
  • Prednisone (Sterapred) 60 mg/m2/day PO days 1-5 (regimen originally was days 1-6, but now is just days 1-5)
  • Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m2 total) (sometimes capped at maximum total dose of 2mg per cycle) continuous IV infusion days 1-4
  • Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m2 total) continuous IV infusion days 1-4
  • Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 5 (regimen originally was day 6, but now is day 5)
  • PCP prophylaxis (choose one)
    • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID 3 days per week
    • Atovaquone (Mepron) 1500mg PO daily
    • Pentamidine (Nebupent) 300 mg nebulized Q28days
  • Filgrastim (Neupogen) 5 mcg/kg SQ daily start day 6 and continue until ANC >5,000/uL past nadir

Q21days x 6-8 cycles

Dose-adjusted EPOCH protocol

  • Start cycle 1 as described above
  • Obtain twice per week CBCs 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 Q21days 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.

Historic dose adjustments for hematologic toxicity

These adjustments were in the original paper for standard EPOCH, which are much less relevant due to growth factor support.
If ANC on day 1 is:

  • >1,500, full dose cyclophosphamide
  • 1,000-1,500, reduce cyclophosphamide by 187 mg/m2 (equal to 25% dose reduction)
  • <1,000, hold EPOCH
  • If ANC nadir is <500, reduce cyclophosphamide an additional 187 mg/m2
  • If ANC nadir is >500 and patient had previously been dose-reduced, increase cyclophosphamide dose by 187 mg/m2

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 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 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

R-EPOCH

Regimen

  • Rituximab (Rituxan) 375mg/m2 IV once per cycle (usually given as outpatient due to reimbursement issues)
  • Etoposide (Vepesid) 50 mg/m2/day (200 mg/m2 total) continuous IV infusion days 1-4
  • Prednisone (Sterapred) 60 mg/m2/day PO days 1-5 (regimen originally was days 1-6, but now is just days 1-5)
  • Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m2 total) (sometimes capped at maximum total dose of 2mg per cycle) continuous IV infusion days 1-4
  • Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m2 total) continuous IV infusion days 1-4
  • Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 5 (regimen originally was day 6, but now is day 5)
  • PCP prophylaxis (choose one)
    • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID 3 days per week
    • Atovaquone (Mepron) 1500mg PO daily
    • Pentamidine (Nebupent) 300 mg nebulized Q28days
  • Filgrastim (Neupogen) 5 mcg/kg SQ daily start day 6 and continue until ANC >5,000/uL past nadir

Q21days x 6-8 cycles

Dose-adjusted R-EPOCH protocol

  • Start cycle 1 as described above
  • Obtain twice per week CBCs 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 Q21days 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.

Historic dose adjustments for hematologic toxicity

These adjustments were in the original paper for standard EPOCH, which are much less relevant due to growth factor support.
If ANC on day 1 is:

  • >1,500, full dose cyclophosphamide
  • 1,000-1,500, reduce cyclophosphamide by 187 mg/m2 (equal to 25% dose reduction)
  • <1,000, hold EPOCH
  • If ANC nadir is <500, reduce cyclophosphamide an additional 187 mg/m2
  • If ANC nadir is >500 and patient had previously been dose-reduced, increase cyclophosphamide dose by 187 mg/m2

References

See references for EPOCH

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 alkalization for urine pH ≥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.

References

  1. 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 protocol PubMed
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