INTERFERON-ALPHA AND INTERFERON-GAMMA IN ADVANCED RENAL-CELL CARCINOMA - TREATMENT RESULTS, SURVIVAL, AND PROGNOSTIC FACTORS IN 81 PATIENTS

Background: Treatment with biological response modifiers such as inter ferons resulted in reproducible responses in patients with renal cell carcinoma without proved benefit on survival and quality of life. Two trials were conducted to define the efficacy and the benefit on surviv al of interferons in the treatment of advanced renal cell carcinoma. P atients and Methods: Prospectively, 81 patients were treated subcutane ously (sc.) with interferon-alpha 2B (IFN-alpha) or interferon-gamma ( IFN-gamma). The first trial was randomized; 30 patients received weekl y 200 mu g IFN-gamma alone, and 30 patients were treated with a combin ation of IFN-alpha 2B (3-6 x 10(6) IU/m(2) 3 times weekly) and interle ukin-2 (IL-2) (4.8-19.2 x 10(6) IU/m(2) 5 times weekly) for 6 weeks. I n the second trial, 21 patients received IFN-alpha 2B (10 x 10(6) IU s c.) combined with gradually escalating doses (15-300 mu g sc.) of gran ulocyte-macrophage colony-stimulating factor (GM-CSF) 3 times weekly f or 12 weeks. Results: The overall response proportion was 12% (5 compl ete and 4 partial responses; CR, PR). In the patient groups treated wi th IFN-alpha 2B, the overall response rate increased up to 20%. The me dian response duration was 10.2 months. The median survival duration w as 12.7 months. A univariate statistical analysis on prognostic factor s (age, sex, Karnofsky performance status, prior nephrectomy, lung met astases only, treatment regimen) showed that only prior nephrectomy wa s a significant prognostic factor for survival. Conclusion: Biological response modifiers such as IFN-alpha or IFN-gamma had minimal antitum origenic activity in patients with renal cell carcinoma. Combination t herapies with IFN-alpha 2B resulted in significant higher response rat es, but this did not translate into prolonged survival. Out of these s tudies only prior nephrectomy was identified as the predictor of longt erm survival. Because of these disappointing results the study of new biological response modifiers remains priority.