Phase I study of 24-hour continuous intravenous infusion of recombinant human tumor necrosis factor.

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 x 10(5) U/m2 (261 micrograms/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 greater than or equal to 3 x 10(5) U/ml2. Maximal plasma levels were 19 U/ml (8.2 ng/ml). No objective tumor responses were observed.