Phase I/II trial of filgrastim (r-metHuG-CSF), CEOP chemotherapy and antiretroviral therapy in HIV-related non-Hodgkin's lymphoma

Background: A phase I/II trial determined the maximum tolerated dose (MTD) of CEOP for AIDS-related non-Hodgkin's lymphoma (NHL) with concurrent filgrastim and antiretroviral therapy. Patients and methods: Fourteen AIDS-NHL patients, chemotherapy-naive and ECOG performance status < 2 received filgrastim 1.0 μg/kg s.c. daily for 3-7 days to assess neutrophil response, followed by CEOP with filgrastim support 10 μg/kg s.c. daily, day 2-14, continued if the absolute neutrophil count (ANC) < 1.2 x 10⁹/l. Two CEOP dose cohorts were used: cohort 1 (5 patients) - cyclophosphamide (C) 500 mg/m², epirubicin (E) 37.5 mg/m², vincristine (O) 2 mg and prednisolone (P) 75 mg/m² daily on days 1-5; cohort 2 (9 patients) - C 750 mg/m², E 50 mg/m², same doses of O and 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 progressions. 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 ≤ 5 cycles with 6 complete responses, 1 partial response and 2 progressions, 6 deaths and 3 alive at > 33 months. DLT (evaluable in 8 patients) occurred in two patients. Median survival for both cohorts was 17 months. Mean relative dose intensity was > 85%. Conclusions: The dosages of CEOP in cohort 1 defined the MTD however the cohort 2 doses with filgrastim and antiretroviral therapy gave an encouraging response, acceptable toxicities and merit further study.