Regimens with or without interferon-alpha as treatment for metastatic melanoma and renal cell carcinoma: an overview of randomized trials

The effect of interferon-alpha (IFN-alpha) as single agent or in combination in the treatment of metastatic malignant melanoma (MM) or of advanced renal cell carcinoma (RCC) has been widely explored in phase II trials. To evaluate the net benefit of IFN-alpha therapy in these diseases, we performed a meta-analysis comprising all available randomized trials comparing regimens with or without IFN-alpha. Data were obtained from the Medline data base, and from the data bases at the National Cancer Institute, Schering-Plough, and Hoffmann-La Roche. A total of six published and five unpublished studies on metastatic MM, as well as six published and two unpublished studies on advanced RCC, comprising altogether 1,164 and 525 patients, respectively, fulfilled our criteria. In MM, the overall response rate for the IFN-alpha-containing regimens was 24% (range, 10-46%), compared with 17% (range, 5-30%) for those without IFN-alpha. In RCC, the overall response rate for IFN-alpha-containing regimens was 14% (range, 4-33%), and 8% (range, 3-27%) for those without IFN-alpha. A meta-analysis showed that regimens including IFN-alpha improved response rates compared with regimens without IFN-alpha. The pooled odds ratio (OR) for improved response with IFN-alpha in metastatic MM was 0.65 95% confidence interval (CI) 0.48 to 0.87], and in advanced RCC the OR was 0.47 (95% CI 0.26-0.85). In five metastatic MM trials and three RCC trials, enough data on survival were reported to estimate a pooled 1-year OR for survival. The pooled OR for improved survival with IFN-alpha was 0.69 (95% CI 0.50-0.94), and 0.46 (95% CI 0.28-0.75), respectively. The data on both metastatic MM and advanced RCC indicate that better response rates and prolonged survival can be achieved with regimens including IFN-alpha. The clinical relevance of these findings will be discussed.