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Phase II Trial of Sorafenib Plus Interferon Alfa-2b As First- or Second-Line Therapy in Patients With Metastatic Renal Cell Cancer

Jared A. Gollob, W. Kimryn Rathmell, Tina M. Richmond, Christine B. Marino, Elizabeth K. Miller, Gayle Grigson, Catharine Watkins, Lin Gu, Bercedis L. Peterson, John J. Wright

From the Division of Medical Oncology, Department of Medicine, and Departments of Biostatistics and Bioinformatics, Duke University Medical Center, Durham; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC; and Investigational Drug Branch, National Cancer Institute, Bethesda, MD

Address reprint requests to Jared A. Gollob, MD, Duke University Medical Center, DUMC 3441, Durham, NC 27710; e-mail: jared.gollob{at}duke.edu

Purpose: We undertook this study to determine the activity and tolerability of sorafenib administered with interferon alfa-2b (IFN--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--2b. Treatment consisted of 8-week cycles of sorafenib 400 mg orally bid plus IFN--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% CI, 19% to 49%; 13 of 40 patients), including 28% partial responses (n = 11) and 5% complete responses (n = 2). Responses were seen in treatment-naïve 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% CI, 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--2b has substantial activity in treatment-naïve 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.

Supported by National Institutes of Health Grants No. K23RR15541 and U01-CA-099118.

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA, and the 3rd International Congress on Kidney and Bladder Cancer, August 4-6, 2006, Orlando, FL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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