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, Calabr├▓ F, Cheng S, Trudel GC, Paliwal P, Sternberg CN.
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.

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).