Phase II Study of Sunitinib Malate, an Oral Multitargeted Tyrosine Kinase Inhibitor, in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane
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Published:2008-04-10
Issue:11
Volume:26
Page:1810-1816
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Burstein Harold J.1, Elias Anthony D.1, Rugo Hope S.1, Cobleigh Melody A.1, Wolff Antonio C.1, Eisenberg Peter D.1, Lehman Mary1, Adams Bonne J.1, Bello Carlo L.1, DePrimo Samuel E.1, Baum Charles M.1, Miller Kathy D.1
Affiliation:
1. From the Dana-Farber Cancer Institute, Boston, MA; University of Colorado Health Sciences Center, Denver, CO; University of California San Francisco, San Francisco; California Cancer Care Inc, Greenbrae; Pfizer Inc, La Jolla; TRACON Pharmaceuticals Inc, San Diego, CA; Rush University Medical Center, Chicago, IL; Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD; and the Indiana University Simon Cancer Center, Indianapolis, IN
Abstract
PurposeSunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC).Patients and MethodsSixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment). The primary end point was objective response rate. Plasma samples were obtained for pharmacokinetic and biomarker analysis.ResultsSeven patients achieved a partial response (median duration, 19 weeks), giving an overall response rate of 11%. Three additional patients (5%) maintained stable disease for ≥ 6 months. Median time to progression and overall survival were 10 and 38 weeks, respectively. Notably, responses occurred in triple negative tumors and HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required dose interruption during ≥ 1 cycle, and 25 patients required dose reduction (39%). Thirty-six patients (56%) had dose modifications due to adverse events (AEs). Treatment was associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) in severity and were effectively managed with dose delays or reductions.ConclusionSunitinib is active in patients with heavily pretreated MBC. Most AEs were of mild-to-moderate severity and manageable with supportive treatment and/or dose modification. Further studies in breast cancer are warranted.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Reference32 articles.
1. Prognostic Value of Vascular Endothelial Growth Factor in Breast Cancer 2. What Is the Evidence That Tumors Are Angiogenesis Dependent? 3. Relf M, LeJeune S, Scott PA, et al: Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res 57:963,1997-969, 4. Yoshiji H, Gomez DE, Shibuya M, et al: Expression of vascular endothelial growth factor, its receptor, and other angiogenic factors in human breast cancer. Cancer Res 56:2013,1996-2016, 5. Price DJ, Miralem T, Jiang S, et al: Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells. Cell Growth Differ 12:129,2001-135,
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