Phase I studies of recombinant interferon-gamma

J Biol Response Mod. 1990 Apr;9(2):185-93.

Abstract

A phase I study of the effects of intravenous administration of interferon-gamma on 31 patients was performed. The effects of dose, schedule, and chronic administration were studied. In the first phase of the study, a dose range of 0.01-500 MU/m2 (0.0002-25 mg/m2) was tested and we found the maximum tolerated dose to be 400 MU/m2; the dose-limiting toxicity with this preparation was hypotension. In the second phase, three different schedules of administration were tested. There were no significant differences in toxicity between a 20 min, a 4 h, or a 24 h infusion of 60 MU/m2 (3 mg/m2). In the third phase, patients received chronic administration of either 1 or 30 MU/m2. Patients given 30 MU/m2 twice a week for 4 weeks showed more symptoms--fever, nausea, and orthostasis--than those treated with 1 MU/m2. No significant changes were seen in natural killer cell activity, antibody-dependent complement cytotoxicity, or monocyte cytotoxicity at any dose. Maximal stimulation of 2',5'-oligodenylate synthetase occurred at low doses (12 MU/m2). Depressed bone marrow colony formation for CFU-GM, BFU-E, and CFU-GEMM in vivo was noted. No objective antitumor responses were noted. This preparation of recombinant interferon-gamma can be given in doses as high as 400 MU/m2. Chronic administration would appear to be limited to 30 MU/m2. However, lower doses may give maximal biologic responses. These studies provide further information on the biologic effects of a wide dose range and a variety of schedules of recombinant interferon-gamma.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 2',5'-Oligoadenylate Synthetase / metabolism
  • Adrenocorticotropic Hormone / blood
  • Adult
  • Aged
  • Antibody-Dependent Cell Cytotoxicity / immunology
  • Bone Marrow Cells
  • Colony-Forming Units Assay
  • Cytotoxicity, Immunologic
  • Dose-Response Relationship, Drug
  • Drug Evaluation
  • Female
  • Humans
  • Hydrocortisone / blood
  • Interferon-gamma / administration & dosage
  • Interferon-gamma / adverse effects*
  • Interferon-gamma / pharmacology
  • Killer Cells, Natural / immunology
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Neoplasms / blood
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Recombinant Proteins

Substances

  • Recombinant Proteins
  • Interferon-gamma
  • Adrenocorticotropic Hormone
  • 2',5'-Oligoadenylate Synthetase
  • Hydrocortisone