PHASE I II TRIAL OF FILGRASTIM (R-METHUG-CSF), CEOP CHEMOTHERAPY AND ANTIRETROVIRAL THERAPY IN HIV-RELATED NON-HODGKINS-LYMPHOMA/

Background: A phase I/II trial determined the maximum tolerated dose ( MTD) of CEOP for AIDS-related non-Hodgkin's lymphoma (NHL) with concur rent filgrastim and antiretroviral therapy. Patients and methods: Four teen AIDS-NHL patients, chemotherapy-naive and ECOG performance status <2 received filgrastim 1.0 mu g/kg s.c. daily for 3-7 days to assess neutrophil response, followed by CEOP with filgrastim support 10 mu g/ kg s.c. daily, day 2-14, continued if the absolute neutrophil count (A NC) <1.2 x 10(9)/1. Two CEOP dose cohorts were used: cohort 1 (5 patie nts)-cyclophosphamide (C) 500 mg/m(2), epirubicin (E) 37.5 mg/m(2), vi ncristine (O)2 mg and prednisolone (P) 75 mg/m(2) daily on days 1-5; c ohort 2 (9 patients) - C 750 mg/m(2), E 50 mg/m(2), same doses of O an d P. Antiretroviral therapy was maintained (zidovudine-10, ddI-3, both -1). Results: In cohort 1, 4/5 patients received at least 3 courses of CEOP with one complete response after five cycles and four progressio ns. Four have died (3-21 months after entry) with 1 alive at 40 months . Dose limiting toxicity (DLT - grade IV febrile neutropenia in cycle 1) occurred in 1 patient. In cohort 2, 5/9 completed greater than or e qual to 5 cycles with 6 complete responses, 1 partial response and 2 p rogressions, 6 deaths and 3 alive at >33 months. DLT (evaluable in 8 p atients) occurred in two patients. Median survival for both cohorts wa s 17 months. Mean relative dose intensity was >85%. Conclusions: The d osages of CEOP in cohort 1 defined the MTD however the cohort 2 doses with filgrastim and antiretroviral therapy gave an encouraging respons e, acceptable toxicities and merit further study.