Phase II trial of capecitabine and rHu-interferon-α-2a in patients with metastatic renal cell carcinoma, limited efficacy, and moderate toxicity

BackgroundCapecitabine is an orally administered fluoropyrimidine that is converted to 5-fluorouracil by thymidine phosphorylase. In view of the recognized synergism of fluoropyrimidines with interferon-α (IFNα), a Phase II study to characterize the toxicity and efficacy of the combination of capecitabine and rHuIFNα-2a for the treatment of patients with renal cell carcinoma (RCC) was conducted.Patients and MethodsEligible patients had metastatic RCC, measurable disease, and no prior systemic therapy. A total of 32 patients were entered into the study. Histologic subtypes included clear cell (n = 28) and nonclear cell (n = 2). Histology was unknown for 2 patients. The first 14 patients were treated with capecitabine 1,000 mg/m2 twice daily on days 1–14 and 22–36, combined with IFNα-2a 3.0 MU/m2 subcutaneously 3 times weekly. Because of toxicity requiring dose reductions during the first cycle, the capecitabine dose was reduced to 825 mg/m2 twice daily on days 1–14 and 22–36 in the subsequent 18 patients.ResultsResponses were seen in 4 of 32 patients (12%) (95% confidence interval 4% to 29%), with 1 complete response and 3 partial responses. There were 3 responses that occurred at the higher capecitabine starting dose level. Median response duration was 12 months (range 4.6–15.0). There were 12 patients (38%) who had stable disease for at least 2 cycles (duration 2.9 to 33.6+ months). One-year survival was 63%. Toxicity was moderate to severe and required dose reductions in 88% of patients. There were 23 patients who had grade ≥3 toxicity.ConclusionThe combination of capecitabine and IFNα-2a has limited activity in metastatic RCC and is associated with moderate-to-severe toxicity.