Clinical and biological effects of recombinant interferon-beta administered intravenously daily in phase I trial

J Interferon Res. 1988 Jun;8(3):357-66. doi: 10.1089/jir.1988.8.357.

Abstract

Interferon-beta serine (IFN-beta ser) was administered intravenously (i.v.) daily for 14 days at doses of 3, 10, 30 X 10(6) units to 19 patients. In this Phase I trial, IFN-beta ser was tolerated without limiting fever or subjective toxicities. At 30 X 10(6) units, 3 patients developed hematologic toxicity and dose escalation was thus terminated. No patient developed detectable binding or neutralizing antibody to IFN-beta. A significant (p less than 0.006) increase in serum beta 2-microglobulin and a significant (less than 0.005) increase in 2',5'-oligoadenylate synthetase (2-5A) in peripheral mononuclear cells were identified. Increase in these proteins did not correlate with dose or with the disappearance of serum IFN over the first 5 h after injection. Two patients, one with renal carcinoma and one with melanoma, had objective responses. This trial further confirms safety and biological potency of this synthetic mutant of IFN-beta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / metabolism
  • Adult
  • Aged
  • Drug Evaluation
  • Female
  • Humans
  • Injections, Intravenous
  • Interferon Type I / administration & dosage*
  • Interferon Type I / adverse effects
  • Interferon Type I / blood
  • Interferon beta-1a
  • Interferon beta-1b
  • Interferon-beta*
  • Male
  • Melanoma / metabolism
  • Melanoma / therapy
  • Middle Aged
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / blood
  • beta 2-Microglobulin / metabolism

Substances

  • Interferon Type I
  • Recombinant Proteins
  • beta 2-Microglobulin
  • Interferon beta-1b
  • Interferon-beta
  • 2',5'-Oligoadenylate Synthetase
  • Interferon beta-1a