Phase I trial of recombinant interferon gamma by 1-hour i.v. infusion

Abstract

Fifteen patients with advanced malignancy were treated with recombinant interferon gamma (rIFN-gamma) (specific activity approximately 2 X 10(7) units/mg, purity greater than 99%) given by 1-hour iv infusion three times a week for 6 weeks, at fixed dose levels of 0.1, 0.5, 1.0, or 2.0 mg/m2/day. The common side effects were constitutional symptoms, including fever, chills, myalgias, and headache, but these were less severe than those observed following daily 6-hour iv infusions. Significant changes in blood cell counts and routine serum chemistries were not observed, but there was a dose-dependent increase in serum triglyceride levels. The maximum safely tolerated dose achieved was 1.0 mg/m2/day. Peak serum interferon levels occurred at the midpoint of the infusion and were dose-dependent. rIFN-gamma was rapidly cleared from serum and no detectable activity was found 2 hours after the infusion. Two patients, both with B-cell malignancies, showed objective evidence of tumor regression during the treatment. Treatment was associated with an increase in serum levels of beta 2-microglobulin and the H2O2 secretory capacity of peripheral blood monocytes. We conclude that rIFN-gamma administered by short iv infusion can induce biological activities and causes less toxicity than when given by prolonged iv infusion.