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Yu EY , Wilding G , Posadas E , Gross M , Culine S , Massard C , Morris MJ , Hudes G , Calabro F , Cheng ST , Trudel GC , Paliwal P , Sternberg CN
Phase II Study of Dasatinib in Patients with Metastatic Castration-Resistant Prostate Cancer
Clinical Cancer Research. 2009 Dec;15(23) :7421-7428
PMID: ISI:000272363700040    PMCID: PMC 3394097   
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Abstract
Purpose: Antiproliferative and antiosteoclastic activity from preclinical models show potential for dasatinib, an oral SRC and SRC family kinase inhibitor, as a targeted therapy for patients with prostate cancer. This phase 11 study investigated the activity of dasatinib in patients with metastatic castration-resistant prostate cancer (CRPC). Experimental Design: Chemotherapy-naive men with CRPC and increasing prostate-specific antigen were treated with dasatinib 100 or 70 mg twice daily. Endpoints included changes in prostate-specific antigen, bone scans, measurable disease (Response Evaluation Criteria in Solid Tumor), and markers of bone metabolism. Following Prostate Cancer Working Group 2 guidelines, lack of progression according to Response Evaluation Criteria in Solid Tumor and bone scan was determined and reported at 12 and 24 weeks. Results: Forty-seven patients were enrolled and received dasatinib (initial dose 100 mg twice daily, n = 25; 70 mg twice daily, n = 22), of whom 41 (87%) had bone disease. Lack of progression was achieved in 20 (43%) patients at week 12 and in 9 (19%) patients at week 24. Of 41 evaluable patients, 21 (51%) patients achieved 40% reduction in urinary N-telopeptide by week 12, with 33 (80%) achieving some level of reduction anytime on study. Of 15 patients with elevated urinary N-telopeptide at baseline, 8 (53%) normalized on study. Of 40 evaluable patients, 24 (60%) had reduction in bone alkaline phosphatase at week 12 and 25 (63%) achieved some reduction on study. Dasatinib was generally well tolerated and treatment-related adverse events were moderate. Conclusions: This study provides encouraging evidence of dasatinib activity in bone and reasonable tolerability in chemotherapy-naive patients with metastatic CRPC. (Clin Cancer Res 2009;15(23):7421-8)
Notes
Yu, Evan Y. Wilding, George Posadas, Edwin Gross, Mitchell Culine, Stephane Massard, Christophe Morris, Michael J. Hudes, Gary Calabro, Fabio Cheng, Shinta Trudel, Geralyn C. Paliwal, Prashni Sternberg, Cora N. Department of Defense Prostate Cancer Clinical Trials Consortium awards [W81XWH-07-1-0097, W81XWH-06-1-0258, W81XWH-06-10241]; Prostate Cancer Foundation Therapy Consortium ; Bristol-Myers Squibb Grant support: Department of Defense Prostate Cancer Clinical Trials Consortium awards W81XWH-07-1-0097, W81XWH-06-1-0258, and W81XWH-06-10241; Prostate Cancer Foundation Therapy Consortium; and Bristol-Myers Squibb. Editorial assistance for this article was provided by StemScientific and funded by Bristol-Myers Squibb. 46 Amer assoc cancer research; 615 chestnut st, 17th floor, philadelphia, pa 19106-4404 usa 527jq