Combination therapy with interferon alfa-2a and interleukin-2 for the treatment of metastatic cancer

Purpose: Here we report the long-term follow-up evaluation of a phase I/II study of toxicity and response of combination interferon alfa-2a (IFNα) and interleukin-2 (IL-2) in patients with metastatic cancer. Patients and Methods: From November 1987 through October 1990, 189 patients were treated with 379 courses. IFNα (3 x 10⁶ U/m²) was administered three times per day as an intravenous (IV) bolus with IV IL-2 2.6 x 10⁶ IU/m² (six patients, group 1), 7.8 x 10⁶ IU/m² (32 patients, group 2), or 11.7 x 10⁶ IU/m² (26 patients, group 3). Subsequently, IFNα dose was escalated to 6 x 10⁶ U/m² plus IL-2 11.7 x 10⁶ IU/m² (22 patients, group 4). Two further dosage schedules of IL-2 were tested at 7.8 x 10⁶ IU/m² (29 patients, group 5) and 15.6 x 10⁶ IU/m² (74 patients, group 6); however, because of IFNα-related toxicity, these two groups received IFNα once per day (6 x 10⁶ U/m²). A treatment course consisted of two cycles (maximum, 15 doses per cycle) separated by a 10-day interval. Results: All patients were assessable for response: 82 patients had melanoma, 75 renal cell carcinoma (RCC), and 16 colorectal cancer. There were two treatment-related deaths. The objective response rate was 23% (43 patients). Response rates were 17%, 19%, 19%, 32%, 41%, and 16%, respectively, for groups 1 through 6. Ten responses are still ongoing (nine in RCC patients) at 57 to 74 months, and 21 patients are alive, for an overall 5-year survival rate of 11%. The median potential follow-up period was 65 months. Although a significantly higher response rate was noted for group 4 (highest dose of IFNα three times per day), no benefit for survival and increased toxicity were noted in this group. Conclusion: Based on these findings, we conclude that further studies of this combination treatment are not warranted.