PHASE-I STUDY OF RECOMBINANT BETA-SER 17 INTERFERON IN THE TREATMENT OF CANCER

Abstract

Fifteen patients with advanced malignancy were treated with escalating doses of recombinant .beta. ser 17 interferon (IFN). Dose ranging from 0.006 to 500 .times. 106 units/m2 were administered according to a dosage escalation scheme by iv push twice weekly (starting 1 week after an initial dose) for a planned minimum of 5 weeks, to be continued as a function of response. Toxic effects were broad in scope but generally low in grade. They included fever, malaise, leukopenia, proteinuria, nausea/vomiting, diarrhea, and mild elevations of serum transaminases and creatinine. In one patient, transient hypotension with bradycardia ensued. Malaise and fever increased somewhat with increasing dose. Doses of up to 500 .times. 106 units/m2 were tolerated without severe toxicity. A maximum tolerated dose was not defined. IFN pharmacokinetics followed a biphasic decay curve, with a distribution phase .alpha.-half-life of 9 minutes and an elimination phase .beta.-half-life of 103 patients. Anti-IFN antibodies by the ELISA technique were present in seven of 15 patients. Presence of antibody did not correlate with toxicity or response. 2'',5''-Adenylate synthetase levels were increase 2 and 24 hours after the initial dose, with a trend toward higher increments with higher doses. Minimal antitumor responses were seen in two patients with melanoma.