title: Biological and clinical effects of interferon-beta ser at two doses.
abstract: To assess biological response, therapeutic activity, and side effects, a randomized, double-blind trial of two doses of interferon-beta ser (IFN-beta ser), differing by 20-fold 4.5 and 90 x 10(6) units), was undertaken in 64 patients with metastatic renal carcinoma. Patients were treated intravenously with injections daily for 10 days with an 11-day rest before treatment was reinitiated. The trial confirmed the relatively good toleration of IFN-beta ser; in the first cycle only 4/63 patients had anorexia of moderate or greater severity. Median weight change over the duration on study was -1.5 kg; in the first cycle only 7% of patients had performance status decline greater than 1 level. Statistically significant changes (p less than 0.05) occurred in granulocytes, lymphocytes, calcium, cholesterol, alkaline phosphatase, and aspartate transferase (AST); however, except for AST, overall clinical differences in the two doses were not great. Of 60 patients evaluated, 1 developed neutralizing antibody. When assessed 24 h after IFN-beta ser at 4.5 x 10(6) units, significant (p less than 0.05) augmentation had occurred in beta 2-microglobulin, HLA-DR, and HLA-DQ expression on monocytes, 2',5'-oligoadenylate (2-5A) synthetase in peripheral mononuclear cells, and natural killer (NK) and K cells functional activity. Although the 90 x 10(6) unit dose also resulted in stimulation of these responses, little additional augmentation of biological response occurred at the higher dose. Except for a decline in monocyte HLA-DR expression, biological responses remained increased at both doses over the 10-day period of treatment. However, no objective regressions of metastatic disease occurred. In view of objective responses in metastatic renal carcinoma in other trials with IFN-beta ser, consideration should be given to alternative schedules.
authors.affiliation: Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
authors.forename: E C
authors.initials: EC
authors.lastname: Borden
authors.forename: J J
authors.initials: JJ
authors.lastname: Rinehart
authors.forename: B E
authors.initials: BE
authors.lastname: Storer
authors.forename: D L
authors.initials: DL
authors.lastname: Trump
authors.forename: D M
authors.initials: DM
authors.lastname: Paulnock
authors.forename: A P
authors.initials: AP
authors.lastname: Teitelbaum
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood; D000328:Adult; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D006680:HLA Antigens; D006801:Humans; D007167:Immunotherapy; D007370:Interferon Type I / Q000008:administration & dosage*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta; D007680:Kidney Neoplasms / Q000503:physiopathology / Q000556:secondary / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage*
chemical_list: D006680:HLA Antigens; D007370:Interferon Type I; D011994:Recombinant Proteins; D000068576:Interferon beta-1b; D016899:Interferon-beta; D015088:2',5'-Oligoadenylate Synthetase; D000068556:Interferon beta-1a