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Phase II Trial of Sunitinib in Patients With Metastatic Colorectal Cancer After Failure of Standard Therapy

Leonard B. Saltz, Lee S. Rosen, John L. Marshall, Robert J. Belt, Herbert I. Hurwitz, S. Gail Eckhardt, Emily K. Bergsland, Daniel G. Haller, A. Craig Lockhart, Caio M. Rocha Lima, Xin Huang, Samuel E. DePrimo, Edna Chow-Maneval, Richard C. Chao, Heinz J. Lenz

From the Memorial Sloan-Kettering Cancer Center, New York, NY; Premiere Oncology, Santa Monica; University of California, San Francisco; Pfizer Global Research and Development, La Jolla; University of Southern California, Los Angeles, CA; Lombardi Cancer Center, Washington, DC; Oncology Hematology of Kansas City, Kansas City, MO; Duke University Medical Center, Durham, NC; University of Colorado Cancer Center, Aurora, CO; University of Pennsylvania, Philadelphia, PA; Vanderbilt University Medical Center, Nashville, TN; and University of Miami, Miami, FL

Address reprint requests to Leonard B. Saltz, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: saltzl{at}mskcc.org

Purpose: Sunitinib is an oral, multitargeted receptor tyrosine kinase inhibitor of the vascular endothelial growth factor receptor and multiple other growth factor receptors. We assessed the safety and efficacy of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy.

Patients and Methods: Eighty-four patients were enrolled onto this two-stage phase II trial and were stratified by whether they had received prior bevacizumab (n = 43) or not (n = 41). Treatment comprised sunitinib 50 mg orally daily for 4 weeks, followed by 2 weeks off treatment, in repeated 6-week cycles.

Results: By Response Evaluation Criteria in Solid Tumors criteria, one patient, who was in the prior bevacizumab cohort, achieved a partial response, and 13 patients (two in the prior bevacizumab cohort and 11 in the no prior bevacizumab cohort) achieved stable disease lasting 22 weeks. Median time to progression in the prior bevacizumab and bevacizumab-naïve cohorts was 2.2 months (95% CI, 1.9 to 2.3 months) and 2.5 months (95% CI, 2.3 to 3.1 months), respectively, whereas median overall survival time was 7.1 months (95% CI, 4.9 to 10.6 months) and 10.2 months (95% CI, 8.2 to 15.3 months), respectively. The most common adverse events were fatigue, diarrhea, nausea, vomiting, and anorexia. Twenty-six patients (32%) required dose reduction to 37.5 mg/d, and one patient required dose reduction to 25 mg/d.

Conclusion: Sunitinib did not demonstrate a meaningful single-agent objective response rate in colorectal cancer refractory to standard chemotherapy. However, the mechanisms of action and acceptable safety profile of sunitinib warrant further study in combination with standard regimens for metastatic colorectal cancer.

Supported by Pfizer Inc.

Presented in part at 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

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

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