BIOLOGICAL AND CLINICAL EFFECTS OF INTERFERON-BETA-SER AT 2 DOSES

To assess biological response, therapeutic activity, and side effects, a randomized, doubleblind 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 > 1 level. Statistically significant changes (p < 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 < 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.