Phase I clinical trial of recombinant human tumor necrosis factor

A phase I and pharmacokinetic study of recombinant tumor necrosis factor (rH-TNF Asahi) was carried out in 29 patients, who received a total of 72 courses with doses ranging from 1 to 48 X 10(4) units/m2. Drug was given as 1-h i.v. infusions. Acute toxicities, taking the form of fever, chills, tachy...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 1987-10, Vol.20 (2), p.137-144
Main Authors: CREAVEN, P. J, PLAGER, J. E, DUPERE, S, HUBEN, R. P, TAKITA, H, MITTELMAN, A, PROEFROCK, A
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Drug Evaluation
Female
Humans
Hypotension - chemically induced
Liver - drug effects
Liver - enzymology
Male
Medical sciences
Middle Aged
Neoplasms - drug therapy
Neoplasms - metabolism
Other treatments
Recombinant Proteins
Treatment. General aspects
Tumor Necrosis Factor-alpha - adverse effects
Tumor Necrosis Factor-alpha - pharmacokinetics
Tumor Necrosis Factor-alpha - therapeutic use
Tumors
Citations: Items that cite this one
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Summary:A phase I and pharmacokinetic study of recombinant tumor necrosis factor (rH-TNF Asahi) was carried out in 29 patients, who received a total of 72 courses with doses ranging from 1 to 48 X 10(4) units/m2. Drug was given as 1-h i.v. infusions. Acute toxicities, taking the form of fever, chills, tachycardia, hypertension, peripheral cyanosis, nausea and vomiting, headache, chest tightness, low back pain, diarrhea and shortness of breath were seen, but were not dose-limiting or dose-related. Some early rise in SGOT, without any change in serum bilirubin, was noted at the highest doses. Eosinophilia, monocytosis, mild hypocalcemia and an increase in fibrin degradation products were seen in a few patients. The dose-limiting toxicity was hypotension, which occurred after the end of the drug infusion and was seen in all 5 patients treated at the highest dose. There was no mortality or long-term morbidity. There were no responses. Pharmacokinetic studies indicated a rapid plasma clearance and a short plasma half-life, generally less than 0.5 h.
ISSN:0344-5704
1432-0843
DOI:10.1007/bf00253968