HIV-associated lymphoma

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CODOX-M/IVAC

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

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

Part 1: CODOX-M

• Cyclophosphamide (Cytoxan) 800 mg/m2 IV on day 1; 200 mg/m2 IV on days 2-5
• Vincristine (Oncovin) 1.5 mg/m2 (max dose of 2 mg) IV on days 1, 8
• Doxorubicin (Adriamycin) 40 mg/m2 IV on day 1
• Cytarabine (Cytosar) 70 mg intrathecal on days 1, 3

Age 65 years or younger:

• Methotrexate (MTX) 300 mg/m2 IV over 1 hour on day 10
• Methotrexate (MTX) 2700 mg/m2 IV over next 23 hours on day 10

Age more than 65 years:

• Methotrexate (MTX) 100 mg/m2 IV over 1 hour on day 10
• Methotrexate (MTX) 900 mg/m2 IV over next 23 hours on day 10

• 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

• Methotrexate (MTX) 12 mg intrathecal on day 15
• Folinic acid (Leucovorin) 15 mg PO once 24 hours after intrathecal methotrexate

Supportive medications:

• Filgrastim (Neupogen) 5 mcg/kg SQ daily, starting on day 13 and continuing until ANC >1,000/uL

Part 2: IVAC

Age 65 years or younger:

• Cytarabine (Cytosar) 2 g/m2 IV over 3 hours Q12H on days 1,2 (4 doses)
• Etoposide (Vepesid) 60 mg/m2 IV over 1 hour on days 1-5
• Ifosfamide (Ifex) 1500 mg/m2 IV over 1 hour on days 1-5
• Mesna (Mesnex) 300 mg/m2 (mixed with ifosfamide) over 1 hour, then 300mg/m2 IV every four hours x 2, on days 1-5

Age more than 65 years:

• Cytarabine (Cytosar) 1 g/m2 IV over 3 hours Q12H on days 1,2 (4 doses)
• Etoposide (Vepesid) 60 mg/m2 IV over 1 hour on days 1-5
• Ifosfamide (Ifex) 1000 mg/m2 IV over 1 hour on days 1-5
• Mesna (Mesnex) 200 mg/m2 (mixed with ifosfamide) over 1 hour, then 200mg/m2 IV every four hours x 2, on days 1-5

• Methotrexate (MTX) 12 mg intrathecal on day 5
• Folinic acid (Leucovorin) 15 mg PO once 24 hours after intrathecal methotrexate

Supportive medications:

• Filgrastim (Neupogen) 5 mcg/kg SQ daily, starting on day 7 and continuing until ANC >1,000/uL

References

1. Magrath I, Adde M, Shad A, Venzon D, Seibel N, Gootenberg J, Neely J, Arndt C, Nieder M, Jaffe E, Wittes RA, Horak ID. Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol. 1996 Mar;14(3):925-34. link to original article contains verified protocol PubMed
2. Wang ES, Straus DJ, Teruya-Feldstein J, Qin J, Portlock C, Moskowitz C, Goy A, Hedrick E, Zelenetz AD, Noy A. Intensive chemotherapy with cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer. 2003 Sep 15;98(6):1196-205. link to original article PubMed

DR-COP

DR-COP: Doxil (pegylated liposomal doxorubicin), Rituximab, Cyclophosphamide, Oncovin, Prednisone

Levels of Evidence: Phase II

Regimen

• Doxorubicin liposomal (Doxil) 40 mg/m2 IV on day 1
• Rituximab (Rituxan) 375 mg/m2 IV on day 1
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV on day 1
• Vincristine (Oncovin) 1.4 mg/m2/day (capped at 2mg) IV on day 1
• Prednisone (Sterapred) 100 mg PO daily on days 1-5
• Antiretroviral therapy is given concomitantly

21 to 28 day cycles up to 6 cycles

Supportive medications:

• Filgrastim (Neupogen) OR Pegfilgrastim (Neulasta) OR Sargramostim (Leukine) starting on day 3 until beyond nadir
• Trimethoprim/Sulfamethoxazole (Bactrim DS) or other PCP/PJP prophylaxis
• Oral quinaolone if CD4 cell count < 100 at entry or during treatment

References

1. Levine AM, Noy A, Lee JY, Tam W, Ramos JC, Henry DH, Parekh S, Reid EG, Mitsuyasu R, Cooley T, Dezube BJ, Ratner L, Cesarman E, Tulpule A. Pegylated Liposomal Doxorubicin, Rituximab, Cyclophosphamide, Vincristine, and Prednisone in AIDS-Related Lymphoma: AIDS Malignancy Consortium Study 047. J Clin Oncol. 2012 Nov 19. [Epub ahead of print] link to original article contains verified protocol PubMed

R-CODOX-M/IVAC

Regimen

To be completed

References

1. Kassam S, Bower M, Lee SM, de Vos J, Fields P, Gandhi S, Nelson M, Montoto S, Tenant-Flowers M, Burns F, Marcus R, Edwards SG, Cwynarski K. A retrospective, multi-center analysis of treatment intensification for HIV-positive patients with high-risk diffuse large B-cell lymphoma. Leuk Lymphoma. 2012 Dec 3. [Epub ahead of print] link to original article PubMed

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

1. 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