Hodgkin lymphoma, nodular lymphocyte-predominant

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Untreated

ABVD

ABVD: Adriamycin, Bleomycin, Vinblastine, Dacarbazine

Regimen

• Doxorubicin (Adriamycin) 25 mg/m2 IV once on days 1 & 15
• Bleomycin (Blenoxane) 10 units/m2 IV once on days 1 & 15 (1 unit test dose with cycle 1 doses, 60 minutes prior to remainder of full dose)
• Vinblastine (Velban) 6 mg/m2 IV once on days 1 & 15
• Dacarbazine (DTIC) 375 mg/m2 IV once on days 1 & 15
• +/- Rituximab (Rituxan); schedule & number of cycles is not well-established. One potential option is 375 mg/m2 IV weekly x 4 weeks on cycle 1 (see single agent rituximab). Use in subsequent cycles is not well-documented.

28-day cycles x 2 to 6 cycles based on stage, response, and whether radiation therapy is used.

References

1. Savage KJ, Skinnider B, Al-Mansour M, Sehn LH, Gascoyne RD, Connors JM. Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood. 2011 Oct 27;118(17):4585-90. link to original article PubMed

CHOP

CHOP: Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone

Regimen

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2mg per cycle) IV once on day 1
• Prednisone (Sterapred) 100 mg PO once daily on days 1 to 5

21-day cycles x 6 to 8 cycles (number of cycles for CHOP in NLPHL is not well-established)

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--this was for diffuse large B-cell lymphomas; no primary reference available for use of CHOP in LPHL PubMed

CVP

CVP: Cyclophosphamide, Vincristine, Prednisone

Regimen

• Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2mg per cycle) IV once on day 1
• Prednisone (Sterapred) 40 mg/m2 PO once daily on days 1 to 5

21-day cycles x up to 8 cycles (number of cycles for CVP in NLPHL is not well-established)

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--this was for follicular lymphoma; no primary reference available for use of CVP in LPHL PubMed

EPOCH

EPOCH: Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin

Regimen #1, Wilson et al. 1993 - original EPOCH protocol

• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m2 total) IV continuous infusion on days 1 to 4
• Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 5 (regimen originally was days 1 to 6, but now is just days 1 to 5)
• Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m2 total) (sometimes capped at maximum total dose of 2mg per cycle) IV continuous infusion on days 1 to 4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m2 total) IV continuous infusion on days 1 to 4
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 5 (regimen originally was day 6, but now is day 5)

Supportive medications:

• PCP prophylaxis (choose one)
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID 3 days per week
  • Atovaquone (Mepron) 1500 mg 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

21-day cycles x 6 to 8 cycles

Regimen #2, Wilson et al. 2002 - dose-adjusted EPOCH

• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m2 total) IV continuous infusion on days 1 to 4
• Prednisone (Sterapred) 60 mg/m2 PO BID on days 1 to 5
• Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m2 total) (not capped in the paper, but sometimes capped at a maximum total dose of 2mg per cycle) IV continuous infusion on days 1 to 4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m2 total) IV continuous infusion on days 1 to 4
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 5

Supportive medications:

• PCP prophylaxis (choose one)
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID 3 days per week
  • Atovaquone (Mepron) 1500 mg 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

21-day cycles x 6 to 8 cycles

Dose-adjustments for EPOCH protocol:

• Start cycle 1 as described above
• Obtain twice per week CBCs for nadir measurements
• If nadir ANC >500, increase Etoposide (Vepesid), Doxorubicin (Adriamycin), and Cyclophosphamide (Cytoxan) 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 (Vepesid), Doxorubicin (Adriamycin), and Cyclophosphamide (Cytoxan) by 20% compared to previous cycle.
• And/or if nadir platelet count <25 on at least 1 measurement, decrease Etoposide (Vepesid), Doxorubicin (Adriamycin), and Cyclophosphamide (Cytoxan) 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 content property of HemOnc.org
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-CHOP

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone

Regimen

• Rituximab (Rituxan) 375 mg/m2 IV once on day 1
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
• Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2mg per cycle) IV once on day 1
• Prednisone (Sterapred) 100 mg PO once daily on days 1 to 5

21-day cycles x 6 to 8 cycles (number of cycles for R-CHOP in NLPHL is not well-established)

References

See references for CHOP

R-CVP

R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

Regimen

• Rituximab (Rituxan) 375 mg/m2 IV once on day 1
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m2 (maximum dose of 2mg per cycle) IV once on day 1
• Prednisone (Sterapred) 40 mg/m2 PO once daily on days 1 to 5

21-day cycles x up to 8 cycles (number of cycles for R-CVP in NLPHL is not well-established)

References

See references for CVP

R-EPOCH

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

Regimen #1, Wilson et al. 1993 - original EPOCH protocol (which did not include rituximab)

• Rituximab (Rituxan) 375 mg/m2 IV once per cycle (usually given as outpatient due to reimbursement issues)
• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m2 total) IV continuous infusion on days 1 to 4
• Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 5 (regimen originally was days 1 to 6, but now is just days 1 to 5)
• Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m2 total) (sometimes capped at maximum total dose of 2mg per cycle) IV continuous infusion on days 1 to 4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m2 total) IV continuous infusion on days 1 to 4
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 5 (regimen originally was day 6, but now is day 5)

Supportive medications:

• PCP prophylaxis (choose one)
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID 3 days per week
  • Atovaquone (Mepron) 1500 mg 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

21-day cycles x 6 to 8 cycles

Regimen #2, Wilson et al. 2002 - dose-adjusted EPOCH

• Rituximab (Rituxan) 375 mg/m2 IV once per cycle (usually given as outpatient due to reimbursement issues)
• Etoposide (Vepesid) 50 mg/m2/day (200 mg/m2 total) IV continuous infusion on days 1 to 4
• Prednisone (Sterapred) 60 mg/m2 PO BID on days 1 to 5
• Vincristine (Oncovin) 0.4 mg/m2/day (1.6 mg/m2 total) (not capped in the paper, but sometimes capped at a maximum total dose of 2mg per cycle) IV continuous infusion on days 1 to 4
• Doxorubicin (Adriamycin) 10 mg/m2/day (40 mg/m2 total) IV continuous infusion on days 1 to 4
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 minutes on day 5

Supportive medications:

• PCP prophylaxis (choose one)
  • Trimethoprim/Sulfamethoxazole (Bactrim DS) (160/800 mg) PO BID 3 days per week
  • Atovaquone (Mepron) 1500 mg 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

21-day cycles x 6 to 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

Rituximab (Rituxan)

Regimen

• Rituximab (Rituxan) 375 mg/m2 IV weekly x 4 weeks

Supportive medications:

• Acetaminophen (Tylenol) 650 mg PO 30 minutes prior to each dose of Rituximab (Rituxan)
• Diphenhydramine (Benadryl) 25 mg PO 30 minutes prior to each dose of Rituximab (Rituxan)

One course of 4 week therapy

References

1. Ekstrand BC, Lucas JB, Horwitz SM, Fan Z, Breslin S, Hoppe RT, Natkunam Y, Bartlett NL, Horning SJ. Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. Blood. 2003 Jun 1;101(11):4285-9. link to original article contains protocol PubMed
2. Ibom VK, Prosnitz RG, Gong JZ, Moore JO, DeCastro CM, Prosnitz LR, Rizzieri DA, Gockerman JP. Rituximab in lymphocyte predominance Hodgkin's disease: a case series. Blood. 2003 Jun 1;101(11):4285-9. link to original article contains protocol PubMed
3. Schulz H, Rehwald U, Morschhauser F, Elter T, Driessen C, Rüdiger T, Borchmann P, Schnell R, Diehl V, Engert A, Reiser M. Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood. 2008 Jan 1;111(1):109-11. link to original article contains protocol PubMed