Background: Treatment with biological response modifiers such as interferons 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 survival of interferons in the treatment of advanced renal cell carcinoma. Patients and Methods: Prospectively, 81 patients were treated subcutaneously (sc.) with interferon-α 2B (IFN-α) or interferon-γ (IFN--y). The first trial was randomized; 30 patients received weekly 200 µg IFN-γ alone, and 30 patients were treated with a combination of IFN-α 2B (3-6 ×106 IU/m2 3 times weekly) and interleukin-2 (IL-2) (4.8-19.2 ×106 IU/m2 5 times weekly) for 6 weeks. In the second trial, 21 patients received IFN-α 2B (10 × 10-6 IU sc.) combined with gradually escalating doses (15-300 µg sc.) of granulocyte-macrophage colony-stimulating factor (GM-CSF) 3 times weekly for 12 weeks. Results: The overall response proportion was 12% (5 complete and 4 partial responses; CR, PR). In the patient groups treated with IFN-α 2B, the overall response rate increased up to 20%. The median response duration was 10.2 months. The median survival duration was 12.7 months. A univariate statistical analysis on prognostic factors (age, sex, Karnofsky performance status, prior nephrectomy, lung metastases only, treatment regimen) showed that only prior nephrectomy was a significant prognostic factor for survival. Conclusion: Biological response modifiers such as IFN-α or IFN-γ had minimal antitumorigenic activity in patients with renal cell carcinoma. Combination therapies with IFN-α 2B resulted in significant higher response rates, but this did not translate into prolonged survival. Out of these studies only prior nephrectomy was identified as the predictor of long-term survival. Because of these disappointing results the study of new biological response modifiers re
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