Sorafenib with interferon alfa-2b as first-line treatment of advanced renal carcinoma: a phase II study of the Southwest Oncology Group.

PURPOSE: This phase II study evaluated the activity of combined treatment with interferon alfa-2b and sorafenib, a Raf and multiple receptor tyrosine kinase inhibitor, in patients with advanced renal carcinoma. PATIENTS AND METHODS: Eligible patients had metastatic or unresectable renal carcinoma with a clear-cell component, no prior systemic therapy, performance status 0 to 1, and measurable disease. Treatment consisted of interferon alfa-2b 10 x 10(6) U subcutaneously three times weekly and sorafenib 400 mg orally bid. The primary end point was confirmed Response Evaluation Criteria in Solid Tumors response rate. RESULTS: Twelve (19%) of 62 assessable patients achieved an objective confirmed response. An additional 31 (50%) had an unconfirmed partial response or stable disease as best response. The median progression-free survival was 7 months (95% CI, 4 to 11 months). The most common adverse events were fatigue, anorexia, anemia, diarrhea, nausea, rigors/chills, leukopenia, fever, and transaminase elevation. Von Hippel-Lindau gene mutations were detected in four (22%) of 18 archival tumor specimens. CONCLUSION: The confirmed response rate for the combination of sorafenib and interferon in advanced renal carcinoma is greater than expected with either interferon or sorafenib alone. The toxicity of this combination is dominated by adverse events common to interferon that limit further development of this regimen.