Phase II Study of Dasatinib in Patients with Metastatic Castration-Resistant Prostate Cancer.

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Clin Cancer Res. 2009 Nov 17. [Epub ahead of print]
Phase II Study of Dasatinib in Patients with Metastatic Castration-Resistant Prostate Cancer.
Yu EY, Wilding G, Posadas E, Gross M, Culine S, Massard C, Morris MJ, Hudes G, Calabrò F, Cheng S, Trudel GC, Paliwal P, Sternberg CN.
Authors'
Affiliations: University of Washington, Seattle, Washington; University
of Wisconsin Carbone Cancer Center, Madison, Wisconsin; University of
Chicago, Chicago, Illinois; Cedars-Sinai Medical Center, Los Angeles,
California; CRLC Val d'Aurelle, Montpellier, France; Institut Gustave
Roussy, Villejuif, France; Memorial Sloan-Kettering Cancer Center, New
York, New York; Fox Chase Cancer Center, Philadelphia, Pennsylvania;
San Camillo Forlanini Hospital, Rome, Italy; and Bristol-Myers Squibb,
Wallingford, Connecticut.

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 II 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):OF1-8).