PHASE-I TRIAL OF RECOMBINANT INTERFERON GAMMA BY 1-HOUR IV INFUSION

  • 1 May 1986
    • journal article
    • research article
    • Vol. 70  (5) , 609-614
Abstract
Fifteen patients with advanced malignancy were treated with recombinant interferon gamma (rIFN-.gamma.) (specific activity .apprx. 2 .times. 107 units/mg, purity > 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 per 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 per 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.