A PHASE-I TRIAL TO ASSESS THE VALUE OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (R-METHUG-CSF, FILGRASTIM) IN ACCELERATING THE DOSE-RATE OF CHEMOTHERAPY FOR INTERMEDIATE AND HIGH-GRADE NON-HODGKINS-LYMPHOMA (NHL)

In a multi-centre phase I study we investigated the possibility of red ucing the interval between courses of standard CHOP (cyclophosphamide 750 mg/m(,) doxorubicin 50 mg/m(2), vincristine 2 mgs day 1, and predn isolone 40 mg/m(2) days 1-8) from 21 days to 15 days and then 10 days using granulocyte colony stimulating factor (r-MetHuG-CSF (Amgen)-filg rastim) to accelerate neutrophil recovery. Patients received CHOP foll owed by G-CSF 5 mu g/kg s.c. from day 2 to the day before the next cou rse (e.g. days 2-14 for the 15-day interval). A total of 28 patients w ith newly diagnosed intermediate grade or high grade NHL were studied. Four patients were studied at a 21-day interval, six patients were tr eated at a 15-day interval and subsequently six patients at a 10-day i nterval. Following analysis of this initial cohort, a further 12 patie nts were evaluated; four at the 15-day interval, and eight at the 10-d ay interval. No dose-limiting toxicity was seen in the four patients r eceiving 21-day CHOP. Dose-limiting toxicity was seen in 4/10 patients treated at the 15-day interval (M:F 7:3, median age 55.5, range 39-67 years). This consisted of infection in two patients, recurrent infect ion and debility in a third, and mucositis in a fourth. Seven patients experienced one or more infectious episodes requiring antibiotics (me dian number of episodes: 2, range 1-4). Fourteen patients (M:F 4:3, me dian age 47.5, range 25-63 years) were treated at the 10-day interval. Dose-limiting toxicity was seen in six patients. This consisted of se vere mucositis in three patients, neutropenia and thrombocytopenia on two separate occasions in one patient, and steroid-induced gastritis i n two patients. Nine patients had one or more documented infections (m edian: 2, range 1-3) requiring antibiotics, of which six were severe ( WHO grade 3 or 4). One patient died of Pneumocystis carinii (PCP) pneu monia. In summary, G-CSF (filgrastim) will facilitate the shortening o f the dosage interval between cycles of CHOP chemotherapy due to accel erated hematological recovery. However, non-hematological toxicity due to the shorter dosage interval is increased and infective episodes ar e frequent. (C) 1996 by John Wiley & Sons, Ltd.