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.
Steinmetz
T
T
Medizinische Klinik I, University of Cologne, F.R.G.
Schaadt
M
M
Gähl
R
R
Schenk
V
V
Diehl
V
V
Pfreundschuh
M
M
D000328:Adult; D000368:Aged; D001772:Blood Cell Count; D001777:Blood Coagulation / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D003967:Diarrhea / Q000139:chemically induced; D004341:Drug Evaluation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005334:Fever / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012119:Respiration / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha