This Article Full Text Full Text (PDF) Publisher's Note Erratum (v26,p514) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Saltz, L. B. Articles by Lenz, H. J. Search for Related Content PubMed Articles by Saltz, L. B. Articles by Lenz, H. J. Related Articles Related Correspondence Social Bookmarking                            What's this?

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Correspondence

• Documentation of Thyroid Function in Clinical Studies With Sunitinib: Why Does It Matter?
  David H. Garfield, Pascal Wolter, Patrick Schöffski, Aleck Hercbergs, and Paul Davis
  JCO 2008 26: 5131-5132 [Full Text]

This article has been cited by other articles:

				M. Zangari, L. M. Fink, F. Elice, F. Zhan, D. M. Adcock, and G. J. Tricot Thrombotic Events in Patients With Cancer Receiving Antiangiogenesis Agents J. Clin. Oncol., October 10, 2009; 27(29): 4865 - 4873. [Abstract] [Full Text] [PDF]

				N. P. van Erp, K. Eechoute, A. A. van der Veldt, J. B. Haanen, A. K.L. Reyners, R. H.J. Mathijssen, E. Boven, T. van der Straaten, R. F. Baak-Pablo, J. A.M. Wessels, et al. Pharmacogenetic Pathway Analysis for Determination of Sunitinib-Induced Toxicity J. Clin. Oncol., September 10, 2009; 27(26): 4406 - 4412. [Abstract] [Full Text] [PDF]

				M. P. Morelli, A. M. Brown, T. M. Pitts, J. J. Tentler, F. Ciardiello, A. Ryan, J. M. Jurgensmeier, and S. G. Eckhardt Targeting vascular endothelial growth factor receptor-1 and -3 with cediranib (AZD2171): effects on migration and invasion of gastrointestinal cancer cell lines Mol. Cancer Ther., September 1, 2009; 8(9): 2546 - 2558. [Abstract] [Full Text] [PDF]

				N. Leung, N. A. Saucier, S. R. Zeldenrust, H. D. Gunderson, and L. D. Cornell Acute renal failure after treatment with sunitinib in a patient with multiple myeloma NDT Plus, August 1, 2009; 2(4): 292 - 294. [Abstract] [Full Text] [PDF]

				K. Burkitt, S. Y. Chun, D. T. Dang, and L. H. Dang Targeting both HIF-1 and HIF-2 in human colon cancer cells improves tumor response to sunitinib treatment Mol. Cancer Ther., May 1, 2009; 8(5): 1148 - 1156. [Abstract] [Full Text] [PDF]

				L. Miele, N. Takebe, and S. P. Ivy The Cancer Stem Cell Hypothesis, Embryonic Signaling Pathways, and Therapeutics: Targeting an Elusive Concept ASCO Educational Book, January 1, 2009; 2009(1): 145 - 156. [Abstract] [Full Text] [PDF]

				R. K. Jain, D. G. Duda, and A. G. Sorensen Emerging Paradigms and Potential Biomarkers of Response and Resistance in Antiangiogenic Therapy of Cancer ASCO Educational Book, January 1, 2009; 2009(1): 716 - 721. [Abstract] [Full Text] [PDF]

				D. H. Garfield, P. Wolter, P. Schoffski, A. Hercbergs, and P. Davis Documentation of Thyroid Function in Clinical Studies With Sunitinib: Why Does It Matter? J. Clin. Oncol., November 1, 2008; 26(31): 5131 - 5132. [Full Text] [PDF]

				B. I. Rini, M. D. Michaelson, J. E. Rosenberg, R. M. Bukowski, J. A. Sosman, W. M. Stadler, T. E. Hutson, K. Margolin, C. S. Harmon, S. E. DePrimo, et al. Antitumor Activity and Biomarker Analysis of Sunitinib in Patients With Bevacizumab-Refractory Metastatic Renal Cell Carcinoma J. Clin. Oncol., August 1, 2008; 26(22): 3743 - 3748. [Abstract] [Full Text] [PDF]

				A. J. Bilchik and J. R. Hecht Perioperative Risks of Bevacizumab and Other Biologic Agents for Hepatectomy: Theoretical or Evidence Based? J. Clin. Oncol., April 10, 2008; 26(11): 1786 - 1788. [Full Text] [PDF]