title: Phase I studies of recombinant interferon-gamma.
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.
authors.affiliation: American Cancer Society, Atlanta, GA 30329.
authors.forename: J
authors.initials: J
authors.lastname: Laszlo
authors.forename: D
authors.initials: D
authors.lastname: Goldstein
authors.forename: J
authors.initials: J
authors.lastname: Gockerman
authors.forename: L
authors.initials: L
authors.lastname: Hood
authors.forename: A T
authors.initials: AT
authors.lastname: Huang
authors.forename: P
authors.initials: P
authors.lastname: Triozzi
authors.forename: W D
authors.initials: WD
authors.lastname: Sedwick
authors.forename: H
authors.initials: H
authors.lastname: Koren
authors.forename: E H
authors.initials: EH
authors.lastname: Ellinwood
authors.forename: C Y
authors.initials: CY
authors.lastname: Tso
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007371:Interferon-gamma / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009369:Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D007371:Interferon-gamma; D000324:Adrenocorticotropic Hormone; D015088:2',5'-Oligoadenylate Synthetase; D006854:Hydrocortisone