title: Recombinant tumour necrosis factor alpha administered subcutaneously or intramuscularly for treatment of advanced malignant disease: a phase I trial.
abstract: The pharmacokinetics, toxicity and biological effects of subcutaneous and intramuscular treatment of cancer patients with recombinant tumour necrosis factor alpha (rTNF-alpha) was investigated. 17 patients suffering from refractory malignant disease were treated with either 1.0 micrograms/m2, 10 micrograms/m2 or 100 micrograms/m2 rTNF-alpha. Vital signs, peripheral blood cell counts, TNF and interferon (IFN) gamma serum levels, neopterin, beta 2-microglobulin, C reactive protein (CRP) and cortisol levels were measured immediately before and 2, 12, 24, 48 and 168 h after the first administration of rTNF-alpha. Tumour response was evaluated after 4 and 12 weeks of treatment. The pharmacokinetics followed the same characteristics as those reported for other cytokines. Major toxicities were dose dependent and comprised fever, constitutional symptoms and hypotension. TNF dependent changes were observed in serum levels of IFN-alpha, CRP, neopterin, beta 2-microglobulin, cortisol and white blood cell counts. No objective tumour response was observed. This study indicated that rTNF-alpha administered subcutaneously or intramuscularly results in measurable TNF serum levels, significant toxicity and biological response in absence of clinical efficacy in patients with advanced cancer.
authors.affiliation: IIIrd Department of Internal Medicine, Johannes Gutenberg University Mainz, Germany.
authors.forename: W E
authors.initials: WE
authors.lastname: Aulitzky
authors.forename: H
authors.initials: H
authors.lastname: Tilg
authors.forename: G
authors.initials: G
authors.lastname: Gastl
authors.forename: R
authors.initials: R
authors.lastname: Mull
authors.forename: R
authors.initials: R
authors.lastname: Flener
authors.forename: W
authors.initials: W
authors.lastname: Vogel
authors.forename: M
authors.initials: M
authors.lastname: Herold
authors.forename: M
authors.initials: M
authors.lastname: Berger
authors.forename: G
authors.initials: G
authors.lastname: Judmaier
authors.forename: C
authors.initials: C
authors.lastname: Huber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004341:Drug Evaluation; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha