Phase I study of recombinant human tumor necrosis factor.
A phase I clinical and pharmacokinetic study of recombinant human tumor necrosis factor (rH-TNF) was conducted in a single dose schedule in 33 patients with advanced cancer. rH-TNF was given by i.v. infusion over 30 min with a starting dose of 1 x 10(5) units/m2. The dose was escalated up to 16 x 10(5) units/m2 according to the modified Fibonacci scheme. Toxic effects were similar but not identical to those reported with interferons and interleukin-2, and included fever, rigors, nausea and vomiting and anorexia in a non-dose-dependent manner, and hypotension, leukocytosis, thrombocytopenia and transient elevation of transaminases (SGOT and SGPT) in an approximately dose-dependent manner. DIC syndrome was observed in one patient who had received 16 x 10(5) units/m2. The dose-limiting toxicities were hypotension, thrombocytopenia and hepatotoxicity, and the maximum tolerated dose in a single i.v. infusion of rH-TNF appeared to be 12 x 10(5) units/m2 when thrombocytopenia and elevation of SGOT and SGPT were taken as the dose-limiting toxicities. However, if hypotension was included, the maximum safely tolerated dose appeared to be 5 x 10(5) units/m2.
Kimura
K
K
Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Taguchi
T
T
Urushizaki
I
I
Ohno
R
R
Abe
O
O
Furue
H
H
Hattori
T
T
Ichihashi
H
H
Inoguchi
K
K
Majima
H
H
D000328:Adult; D000368:Aged; D001773:Blood Cells / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002986:Clinical Trials as Topic; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010976:Platelet Count; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha