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Cancer Chemotherapy and Pharmacology

, Volume 20, Issue 3, pp 223–229 | Cite as

Phase I study of recombinant human tumor necrosis factor

  • Kiyoji Kimura
  • Tetsuo Taguchi
  • Ichiro Urushizaki
  • Ryuzo Ohno
  • Osahiko Abe
  • Hisashi Furue
  • Takao Hattori
  • Hidehito Ichihashi
  • Kiyoshi Inoguchi
  • Hisashi Majima
  • Hisanobu Niitani
  • Kazuo Ota
  • Tatsuo Saito
  • Shoji Suga
  • Yozo Suzuoki
  • Akira Wakui
  • Kazumasa Yamada
  • The A-TNF Cooperative Study Group
Original Articles Human Tumor Necrosis Factor

Summary

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 1x105 units/m2. The dose was escalated up to 16x105 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 16x105 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 12x105 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 5x105 units/m2.

Keywords

Cancer Research Tumor Necrosis Interferon Tumor Necrosis Factor Single Dose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • Kiyoji Kimura
  • Tetsuo Taguchi
  • Ichiro Urushizaki
  • Ryuzo Ohno
    • 1
  • Osahiko Abe
  • Hisashi Furue
  • Takao Hattori
  • Hidehito Ichihashi
  • Kiyoshi Inoguchi
  • Hisashi Majima
  • Hisanobu Niitani
  • Kazuo Ota
  • Tatsuo Saito
  • Shoji Suga
  • Yozo Suzuoki
  • Akira Wakui
  • Kazumasa Yamada
  • The A-TNF Cooperative Study Group
  1. 1.Department of Internal MedicineNagoya University School of MedicineNagoyaJapan

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