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Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors

Matthew H. Kulke, Heinz-Josef Lenz, Neal J. Meropol, James Posey, David P. Ryan, Joel Picus, Emily Bergsland, Keith Stuart, Lesley Tye, Xin Huang, Jim Z. Li, Charles M. Baum, Charles S. Fuchs

From the Dana-Farber Cancer Institute; Massachusetts General Hospital; Beth Israel Deaconess Medical Center, Boston, MA; University of Southern California Norris Comprehensive Cancer Center, Los Angeles; University of California, San Francisco Comprehensive Cancer Center, San Francisco; Pfizer Global Research and Development, La Jolla, CA; Fox Chase Cancer Center, Philadelphia, PA; University of Alabama, Birmingham, AL; and Washington University, St Louis, MO

Corresponding author: Matthew Kulke, MD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, e-mail: Matthew_Kulke{at}dfci.harvard.edu

Purpose Standard cytotoxic chemotherapy has limited efficacy in metastatic neuroendocrine tumor patients. Neuroendocrine tumors express vascular endothelial growth factor (VEGF) and its receptor (VEGFR). Sunitinib malate, an oral tyrosine kinase inhibitor, has activity against VEGFRs as well as platelet-derived growth factor receptors, stem-cell factor receptor, glial cell line–derived neurotrophic factor, and FMS-like tyrosine kinase-3. We evaluated the efficacy of sunitinib in a two-cohort, phase II study of advanced carcinoid and pancreatic neuroendocrine tumor patients.

Patients and Methods Patients were treated with repeated 6-week cycles of oral sunitinib (50 mg/d for 4 weeks, followed by 2 weeks off treatment). Patients were observed for response, survival, and adverse events. Patient-reported outcomes were assessed.

Results Among 109 enrolled patients, 107 received sunitinib (carcinoid, n = 41; pancreatic endocrine tumor, n = 66). Overall objective response rate (ORR) in pancreatic endocrine tumor patients was 16.7% (11 of 66 patients), and 68% (45 of 66 patients) had stable disease (SD). Among carcinoid patients, ORR was 2.4% (one of 41 patients), and 83% (34 of 41 patients) had SD. Median time to tumor progression was 7.7 months in pancreatic neuroendocrine tumor patients and 10.2 months in carcinoid patients. One-year survival rate was 81.1% in pancreatic neuroendocrine tumor patients and 83.4% in carcinoid patients. No significant differences from baseline in patient-reported quality of life or fatigue were observed during treatment.

Conclusion Sunitinib has antitumor activity in pancreatic neuroendocrine tumors; its activity against carcinoid tumors could not be definitively determined in this nonrandomized study. Randomized trials of sunitinib in patients with neuroendocrine tumors are warranted.

Supported by Pfizer Inc. M.H.K. acknowledges additional support from the Caring for Carcinoid Foundation, Dr Raymond and Beverly Sackler, and the Stephen and Caroline Kaufer fund for neuroendocrine tumor research.

Sources of preliminary data are listed in the Appendix available online.

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

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