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Updated: Jun 18, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Phase II study of dasatinib in patients with metastatic castration-resistant prostate cancer
Evan Y Yu1, George Wilding, Edwin Posadas
1University of Washington, Seattle, Washington, USA.
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 > or =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.
Insights
Dasatinib showed promising anti-cancer effects in patients with metastatic castration-resistant prostate cancer (CRPC). The drug demonstrated activity in bone and was well-tolerated, offering a potential new therapy for CRPC.
Area of Science:
- Oncology
- Pharmacology
Background:
- Metastatic castration-resistant prostate cancer (CRPC) presents a significant therapeutic challenge.
- Dasatinib, an oral SRC and SRC family kinase inhibitor, exhibits antiproliferative and antiosteoclastic activity in preclinical models.
- Targeted therapy with dasatinib is being investigated for prostate cancer.
Purpose of the Study:
- To investigate the activity and tolerability of dasatinib in patients with metastatic castration-resistant prostate cancer (CRPC).
- To evaluate dasatinib as a targeted therapy for chemotherapy-naive men with CRPC.
Main Methods:
- A phase II study treated chemotherapy-naive men with CRPC using dasatinib at 100 mg or 70 mg twice daily.
- Endpoints included changes in prostate-specific antigen (PSA), bone scans, measurable disease, and bone metabolism markers.
- Progression was assessed at 12 and 24 weeks based on Response Evaluation Criteria in Solid Tumors (RECIST) and bone scan criteria.
Main Results:
- Forty-seven patients received dasatinib; 41 (87%) had bone disease.
- Lack of progression was observed in 43% at 12 weeks and 19% at 24 weeks.
- Significant reductions in bone turnover markers (urinary N-telopeptide and bone alkaline phosphatase) were noted, with 53% of patients with elevated N-telopeptide normalizing the marker.
Conclusions:
- Dasatinib demonstrated encouraging activity in bone and was generally well-tolerated in chemotherapy-naive patients with metastatic CRPC.
- These findings support dasatinib as a potential targeted therapy for this patient population.
