Outpatient treatment with subcutaneous interleukin-2 and interferon alfa administration in combination with fluorouracil in patients with metastatic renal cell carcinoma: results of a sequential nonrandomized phase II study. Subcutaneous Administration Propeukin Program Cooperative Group.

PURPOSE We report the results of the Subcutaneous Administration Propeukin Program (SCAPP) II trial of an outpatient treatment in renal cell carcinoma using interleukin-2 (IL-2) and interferon alfa-2a (IFN-alpha) administered subcutaneously in combination with fluorouracil (5-FU). The objective of this multicenter trial was to confirm that the combination of IL-2, IFN-alpha, and 5-FU leads to a response rate greater than 20%. PATIENTS AND METHODS Patients with metastatic renal cell carcinoma were included in this study. During the induction phase of the treatment, which lasted 10 weeks, IL-2 and IFN-alpha were administered subcutaneously three times a week for 8 weeks at doses of 18 MIU and 9 MIU, respectively. During these 8 weeks, every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. After evaluation, responding patients or patients with stable disease (SD) were given maintenance treatment, until disease progression (PD) or the appearance of unacceptable toxicity. Each maintenance cycle consisted of a 2-week treatment followed by a three-week rest period. During treatment, IL-2 and IFN-alpha were administered subcutaneously three times a week at doses of 18 MIU and 9 MIU, respectively. Every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. RESULTS This trial was closed when the sixth sequential analysis showed the lack of benefit from this combination. At the end of the induction period, of 62 patients, 12 (19%; 95% confidence interval [CI], 10% to 31%) reached an objective response, including one complete response (CR), 16 presented with SD, and 27 showed PD. Twenty-seven patients (43%) developed severe toxicity that required reduction of the planned doses (13 patients), delayed treatment (eight patients), or treatment termination (six patients). Seventeen patients were given maintenance treatment. One- and 2-year survival rates were estimated at 55% and 33%, respectively. The 2-year survival rate was 15% in 11 patients who presented with three poor-prognosis factors and 41% in 51 patients who initially presented with no, one, or two poor-prognosis factors (P = .04). CONCLUSION As in other recently published studies that used 5-FU, IL-2, and IFN-alpha, the multicenter SCAPP II trial in patients with metastatic renal cell carcinoma generated severe toxicity. This sequential trial failed to confirm the favorable results previously obtained by Atzpodien and Sella with this combination of three drugs. Its efficacy, assessed on the response and survival rates, is near to the results observed in programs that used IL-2 alone given subcutaneously.