Recombinant human tumor necrosis factor administered as a 24-hour intravenous infusion. A phase I and pharmacologic study

J Natl Cancer Inst. 1988 Sep 7;80(13):1039-44. doi: 10.1093/jnci/80.13.1039.


Recombinant human tumor necrosis factor (rH-TNF) is a cytokine with direct antitumor properties. In a phase I trial we continuously infused rH-TNF for 24 hours. We gave a total of 115 courses of therapy to 50 patients. Doses ranged from 4.5 to 645 micrograms of rH-TNF/m2. Systemic toxicity, including fever, chills, fatigue, and hypotension, increased with the dose of rH-TNF administered. Doses greater than 454 micrograms/m2 frequently caused severe lethargy and fatigue, which precluded hospital discharge of the patient at the completion of therapy. The dose-limiting toxicity was hypotension, and five patients treated at the two highest dose levels required dopamine treatment. Other organ-specific toxicity was modest and spontaneously resolved after 48 hours. The 24-hour infusions of rH-TNF were associated with significant decreases in serum cholesterol and high-density lipoprotein levels. Pharmacokinetic studies using an enzyme-linked immunosorbent assay demonstrated peak plasma rH-TNF levels of 90-900 pg/mL. Despite continuous infusion of rH-TNF, no steady-state level was achieved. The recommended phase II dose for rH-TNF as a 24-hour continuous infusion is 545 micrograms/m2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Drug Evaluation
  • Humans
  • Hypotension / chemically induced
  • Infusions, Intravenous
  • Middle Aged
  • Neoplasms / therapy*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / blood
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / adverse effects*
  • Tumor Necrosis Factor-alpha / blood


  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha