A prospective, non-randomised phase 1-2 trial of VACOP-B with filgrastim support for HIV-related non-Hodgkin's lymphoma.

Abstract

Non-Hodgkin's lymphoma (NHL) remains an important complication of associated HIV infection despite advances in antiretroviral therapy (ART), and the optimum chemotherapy regimen for this disease remains to be defined. A dose-escalation trial was performed to determine the maximum tolerated doses of etoposide and doxorubicin as part of the 12-week VACOP-B regimen, supported by filgrastim (r-metHuG-CSF). Patients with aggressive histology HIV-related NHL who were previously untreated with chemotherapy, and who had no active opportunistic infection were eligible for the study. Chemotherapy consisted of cyclophosphamide 350 mg/m2, vincristine 2 mg, bleomycin 10 U/m2; and prednisone 100 mg q2 days x 12 weeks, with increasing doses of doxorubicin 25-50 mg/m2 and etoposide 25-50 mg/m2 intravenously and 50-100 mg/m2 orally. Central nervous system prophylaxis (intrathecal cytarabine 50 mg x 4 doses), antifungal, and Pneumocystis carinii prophylaxis were used, and filgrastim was administered to prevent neutropenic complications. One dose level was expanded to permit the concomitant use of ART. Endpoints were determination of maximum tolerated dose of doxorubicin and etoposide, treatment tolerability, and survival. Forty-seven patients were enrolled, most with diffuse large-cell or immunoblastic NHL. Protocol-defined maximum tolerated dose was not reached and the limits of dose-limiting toxicity were not exceeded, even in patients receiving ART. Thirty-two cycles (4.9%) were delayed >6 days because of toxicity; 30 patients (64%) completed all 12 weeks of treatment. After completion of therapy, 14 patients had a complete response (30%), and 4 had a partial response (8%). Median time to progression was 9 months. At 42 months, progression-free survival was 25% and overall survival was 28%.

• Authors: Carol Anne Sawka, Frances A Shepherd, Edmee Franssen, Joseph Brandwein, Dale A Dotten, Jean-Pierre G Routy, Irwin R Walker, Jean St-Louis, Marianne Taylor, Karen Arts, Michael Crump, MaryAnn Foote
• Journal: Biotechnology annual review (Biotechnol Annu Rev) Vol. 11 Pg. 381-9 ( 2005) ISSN: 1387-2656 [Print] Netherlands
• PMID: 16216784 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Recombinant Proteins
• Bleomycin
• Granulocyte Colony-Stimulating Factor
• Vincristine
• Etoposide
• Doxorubicin
• Cyclophosphamide
• Filgrastim
• Prednisone

Topics

• Administration, Oral
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Bleomycin (adverse effects, therapeutic use)
• CD4 Lymphocyte Count
• Cyclophosphamide (adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Doxorubicin (administration & dosage, adverse effects, therapeutic use)
• Etoposide (administration & dosage, adverse effects, therapeutic use)
• Female
• Filgrastim
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Humans
• Injections, Intravenous
• Injections, Subcutaneous
• Lymphoma, AIDS-Related (drug therapy)
• Lymphoma, Non-Hodgkin (drug therapy)
• Male
• Middle Aged
• Prednisone (adverse effects, therapeutic use)
• Prospective Studies
• Recombinant Proteins
• Survival Analysis
• Treatment Outcome
• Vincristine (adverse effects, therapeutic use)