Could Interferon Still Play a Role in Metastatic Renal Cell Carcinoma? A Randomized Study of Two Schedules of Sorafenib Plus Interferon-Alpha 2a (RAPSODY)

Background: Sorafenib has proven efficacy in metastatic renal cell carcinoma (mRCC). Interferon (IFN) has antiangiogenic activity that is thought to be both dose-and administration-schedule dependent. Objective: To compare two different schedules of IFN combined with sorafenib. Design, setting, and participants: Single-stage, prospective, noncomparative, randomized, open-label, multicenter, phase 2 study on previously untreated patients with mRCC and Eastern Cooperative Oncology Group performance status 0-2. Intervention: Sorafenib 400 mg twice daily plus subcutaneous IFN, 9 million units (MU) three times a week (Arm A) or 3 MU five times a week (Arm B). Outcome measurements and statistical analysis: Primary end points were progression-free survival (PFS) for each arm and safety. Data were evaluated according to an intent-to-treat analysis. Results and limitations: A total of 101 patients were evaluated. Median PFS was 7.9 mo in Arm A and 8.6 mo in Arm B (p = 0.049) and the median duration of response was 8.5 and 19.2 mo, respectively (p = 0.0013). Nine partial responses were observed in Arm A, and three complete and 14 partial responses were observed in Arm B (17.6% vs 34.0%; p = 0.058); 24 and 21 patients (47% and 42%), respectively, achieved stable disease. The most common grade 3-4 toxicities were fatigue plus asthenia (28% vs 16%; p = 0.32) and hand-foot skin reactions (20% vs 18%). Conclusions: Sorafenib plus frequent low-dose IFN showed good efficacy and tolerability. Further investigations should be warranted to identify a possible positioning of this intriguing regimen (6% complete response rate) in the treatment scenario of mRCC. (C) 2012 Published by Elsevier B. V. on behalf of European Association of Urology.