title: Phase I study of recombinant human tumor necrosis factor-alpha in patients with advanced malignancies.
abstract: A clinical phase I trial with recombinant human tumor necrosis factor-alpha (rTNF-alpha) was performed in 30 patients with advanced malignancies. The maximal tolerated dose (MTD) by 3 times weekly intramuscular (i.m.) application was 150 micrograms m-2. Main subjective toxicities including chills, fever, hypotension, fatigue, and anorexia were dose-related. In addition, transient changes in hematologic parameters and lipid metabolism were noted. Two out of 25 evaluated patients showed a minor tumor response after eight weeks of therapy. There was evidence for an improvement of in vivo immuneresponsiveness as revealed from positive delayed type hypersensitivity (DTH) skin tests of 3 out of 6 pretherapeutically anergic patients. We conclude from this phase I trial that rTNF-alpha can be safely administered at doses up to 150 micrograms m-2 i.m., 3 times weekly, without evidence of cumulative toxicity in long-term treatment.
authors.affiliation: Department of Internal Medicine, University of Göttingen, FRG.
authors.forename: H H
authors.initials: HH
authors.lastname: Bartsch
authors.forename: G A
authors.initials: GA
authors.lastname: Nagel
authors.forename: R
authors.initials: R
authors.lastname: Mull
authors.forename: R
authors.initials: R
authors.lastname: Flener
authors.forename: K
authors.initials: K
authors.lastname: Pfizenmaier
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha