A phase II study of interferon alpha and low-dose subcutaneous interleukin-2 in advanced renal cell carcinoma

The activity of the drugs employed in the treatment of metastatic renal cell carcinoma, including biological response modifiers, is limited; one of the aims of clinical research in this area is to maintain the benefits of treatment whilst reducing its toxicity to a minimum level. We have evaluated toxicity and response of the combined administration of recombinant interferon alpha (IFN alpha) and low-dose subcutaneous (s.c.) recombinant interleukin-2 (IL-2) in patients with advanced renal cell carcinoma. A group of 20 previously untreated patients with advanced renal cell carcinoma were included in the study. Treatment consisted of 3 MU/m2 recombinant IFN alpha daily i.m. continuously, and 0.5 MU/m2 recombinant IL-2 twice a day s.c. on days 1-5 for the first week, followed by 1 MU/m2 twice a day for 5 days in the following weeks. For IL-2, a 1-week rest was allowed after 4 weeks of treatment. Response was assessed after 3 months of therapy. Three objective responses were seen, one complete and two partial. Eight patients had stable disease. The median time to progression was 6 months; the median survival for all patients was 14 months. Side-effects were low, limited to grades 1 and 2 in the majority of patients, and included fever, anemia, leukopenia, dyspnea, and abnormalities of liver and renal function tests. Any flu-like syndrome was judged moderate in most patients; however, one-third of the patients refused treatment mostly because of the flu-like syndrome. One of these was the patient experiencing a complete response, who virtually received IFN alpha alone. This regimen, similar to others employed in the treatment of advanced renal cell carcinoma, produced a 15% response rate (95% confidence interval, 0-31%) with 14 months median survival, moderate toxicity and low cost, and required no hospitalization. These data seem to indicate an effectiveness comparable to, and a toxicity lower than, that of regimens employing higher doses of IL-2.