PHASE-I/II STUDY OF RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN PATIENTS WITH ADVANCED MALIGNANCY

The toxicity and hematologic effects of Escherichia coli-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) were studied in 58 treatment cycles in Japanese patients with advanced malignancy as a phase I/II clinical trial. rhGM-CSF in doses from 30 to 250-mu-g/m2/day administered by 24-hour continuous intravenous infusion, 8-hour intravenous, or a daily subcutaneous injection for 14 days. The most common adverse drug events (ADE) were fever, nausea/vomiting, diarrhea, skin eruption, and phlebitis. The frequency of moderate and severe ADE was 2.9, 14.7, 35.3 and 47.1% at 30,60, 125, 250-mu-g/M2/day, respectively. In terms of administration routes, the frequency of ADE was 69% with 24-hour continuous intravenous infusion, 39.1% with 8-hour intravenous infusion and 16.7% with subcutaneous injection. Regarding the hematologic effects of rhGM-CSF, leukopenia improved in a dose-dependent manner. The appropriate dose level to be used in the phase II study was estimated to be in the range between and 250-mu-g/m2/day.