Phase I study of recombinant human tumor necrosis factor

Cancer Chemother Pharmacol. 1987;20(3):223-9. doi: 10.1007/BF00570490.


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.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Blood Cells / drug effects
  • Blood Pressure / drug effects
  • Clinical Trials as Topic
  • Drug Evaluation
  • Female
  • Humans
  • Kidney / drug effects
  • Leukocyte Count
  • Liver / drug effects
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Platelet Count
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / therapeutic use
  • Recombinant Proteins / toxicity
  • Tumor Necrosis Factor-alpha / pharmacokinetics
  • Tumor Necrosis Factor-alpha / therapeutic use*
  • Tumor Necrosis Factor-alpha / toxicity


  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha