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Phase I study of recombinant human tumor necrosis factor

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  • Human Tumor Necrosis Factor
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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.

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Authors and Affiliations

  1. Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsurumaicho, Showaku, 466, Nagoya, Japan

    Ryuzo Ohno

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  1. Kiyoji Kimura
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  2. Tetsuo Taguchi
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  3. Ichiro Urushizaki
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  4. Ryuzo Ohno
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  5. Osahiko Abe
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  6. Hisashi Furue
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  15. Yozo Suzuoki
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  17. Kazumasa Yamada
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The A-TNF Cooperative Study Group

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Kimura, K., Taguchi, T., Urushizaki, I. et al. Phase I study of recombinant human tumor necrosis factor. Cancer Chemother. Pharmacol. 20, 223–229 (1987). https://doi.org/10.1007/BF00570490

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  • DOI: https://doi.org/10.1007/BF00570490

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