A phase I study of recombinant interferon gamma administered by s.c. injection three times per week in patients with...

Human recombinant DNA interferon gamma (IFN-G), with a specific activity of 2 X 10(6) IU/mg protein, was administered s.c. 3 days per week for 2 months to patients with solid tumors. The maximum tolerated dose (MTD) was 10 X 10(6) IU/m2 (5.0 mg/m2) per injection, and six patients were treated at the MTD. Two of these ceased treatment because of severe subjective toxicity (headache, rigors and pyrexia) and three patients developed WHO grade 3 leucopenia. Subjective toxicity varied considerably between patients and some patients at low dose levels experienced severe constitutional symptoms whilst others treated at the MTD had few side effects. These differences were unrelated to pharmacokinetic parameters. Bioavailability of this IFN-G administered s.c. was very variable from one patient to another at the same dose level. We therefore counsel caution in using this IFN-G preparation s.c. in phase II studies.