Phase I study of recombinant human tumor necrosis factor

Autor: Akira Wakui, Tetsuo Taguchi, Hisashi Majima, Tatsuo Saito, Shoji Suga, Ichiro Urushizaki, Kiyoji Kimura, Ota K, Hisanobu Niitani, Hidehito Ichihashi, Takao Hattori, Osahiko Abe, Kiyoshi Inoguchi, Ryuzo Ohno, Kazumasa Yamada, Hisashi Furue, Yozo Suzuoki
Rok vydání: 1987
Předmět:
Zdroj: Cancer Chemotherapy and Pharmacology. 20:223-229
ISSN: 1432-0843
0344-5704
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: