Phase II trial of sorafenib plus interferon alfa-2b as first- or second-line therapy in patients with metastatic renal cell cancer

Purpose We undertook this study to determine the activity and tolerability of sorafenib administered with interferon alfa-2b ( IFN-alpha-2b) as first-or second-line therapy in metastatic renal cell cancer ( RCC). Patients and Methods Between November 2004 and October 2006, 40 patients at two sites were enrolled onto a phase II trial of sorafenib plus IFN-alpha-2b. Treatment consisted of 8-week cycles of sorafenib 400 mg orally bid plus IFN-alpha-2b 10 million U subcutaneously three times a week followed by a 2-week break. Patients were eligible to receive additional cycles of therapy until disease progression. Dose reduction of both drugs by 50% was permitted once for toxicity. Results The response rate was 33% ( 95% Cl, 19% to 49%; 13 of 40 patients), including 28% partial responses ( n = 11) and 5% complete responses ( n = 2). Responses were seen in treatment-nai ve and interleukin-2 ( IL-2) -treated patients within the first two cycles. The median duration of response was 12 months. With a median follow-up time of 14 months, median progression-free survival time was 10 months ( 95% Cl, 8 to 18 months), and median overall survival time has not yet been reached. Fatigue, anorexia, anemia, diarrhea, hypophosphatemia, rash, nausea, and weight loss were the most common toxicities. Grade 3 toxicities were uncommon but included hypophosphatemia, neutropenia, rash, fatigue, and anemia. Dose reductions were required in 65% of patients. Conclusion The combination of sorafenib and IFN-alpha-2b has substantial activity in treatment-nai r ve and IL-2 -treated patients with RCC. The toxicity exceeded that of either drug alone, but dose reductions and breaks between cycles allowed for chronic therapy. A larger, randomized trial would determine whether there is any advantage to this regimen compared with sorafenib alone.