title: A phase I clinical trial of recombinant human tumor necrosis factor given daily for five days.
abstract: A phase I trial of human recombinant tumor necrosis factor (rH-TNF) has been carried out in patients with advanced solid tumors. Sixty-six courses of the drug were given by 1 h IV infusion, daily for 5 days to 33 patients at doses of 5, 10, 20, 30, 45, 60, and 80 x 10(4) U/m2/day. All patients received isotonic saline (up to 21/day) and either indomethacin or ketoprofen. Acute toxicity resembled that seen with the phase I study of a single dose (5). Dose limiting toxicity was acute, rapidly reversible, hepatic dysfunction and hypotension. Hypertension during drug infusion and dyspnea were marked in some patients. There was one complete and one minor response, both in patients with renal cell carcinoma. The dose of 80 x 10(4) U/m2/day x 5 was poorly tolerated and the recommended starting dose for phase II studies is 60 x 10(4) U/m2/day x 5. Caution is recommended in treating patients with pre-existing hepatic function abnormalities, hypertension, hypotension or significant obstructive airway disease.
authors.affiliation: Department of Clinical Pharmacology, Roswell Park Memorial Institute, New York State Department of Health, Buffalo.
authors.forename: P J
authors.initials: PJ
authors.lastname: Creaven
authors.forename: D E
authors.initials: DE
authors.lastname: Brenner
authors.forename: J W
authors.initials: JW
authors.lastname: Cowens
authors.forename: R P
authors.initials: RP
authors.lastname: Huben
authors.forename: R M
authors.initials: RM
authors.lastname: Wolf
authors.forename: H
authors.initials: H
authors.lastname: Takita
authors.forename: S G
authors.initials: SG
authors.lastname: Arbuck
authors.forename: M S
authors.initials: MS
authors.lastname: Razack
authors.forename: A D
authors.initials: AD
authors.lastname: Proefrock
mesh_terms: D000328:Adult; D000368:Aged; D001773:Blood Cells / Q000187:drug effects; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha