PHASE-I STUDY OF 24-HOUR CONTINUOUS INTRAVENOUS-INFUSION OF RECOMBINANT HUMAN-TUMOR NECROSIS FACTOR

Abstract

Sixteen patients with cancer were treated with a 24-h continuous intravenous infusion of recombinant human tumor necrosis factor (rHuTNF) to investigate the spectrum of side-effects, the maximum tolerated dose, the pharmacokinetics, and possible antitumor effects. Fever, chills, and flu-like symptoms were the most common side-effects. The maximum tolerated dose was 6 .times. 105 U/m2 (261 .mu.g/m2). Severe hypotension, fluid retention, watery diarrhea, and central nervous deficits culminated in a profound prostration as the dose-limiting toxicity. No allergic reactions, positive skin tests, or antibodies against rHuTNF were observed. Plasma levels of rHuTNF were detected at doses of .gtoreq. 3 .times. 105 U/m2. Maximal plasma levels were 19 U/ml (8.2 ng/ml). No objective tumor responses were observed.