Phase I studies of recombinant interferon-gamma.
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.
Laszlo
J
J
American Cancer Society, Atlanta, GA 30329.
Goldstein
D
D
Gockerman
J
J
Hood
L
L
Huang
A T
AT
Triozzi
P
P
Sedwick
W D
WD
Koren
H
H
Ellinwood
E H
EH
Tso
C Y
CY
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
D011994:Recombinant Proteins; D007371:Interferon-gamma; D000324:Adrenocorticotropic Hormone; D015088:2',5'-Oligoadenylate Synthetase; D006854:Hydrocortisone