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Dasatinib combined with docetaxel for castration-resistant prostate cancer†
Results from a phase 1-2 study
Article first published online: 4 MAR 2011
Copyright © 2011 American Cancer Society
Volume 118, Issue 1, pages 63–71, 1 January 2012
How to Cite
Araujo, J. C., Mathew, P., Armstrong, A. J., Braud, E. L., Posadas, E., Lonberg, M., Gallick, G. E., Trudel, G. C., Paliwal, P., Agrawal, S. and Logothetis, C. J. (2012), Dasatinib combined with docetaxel for castration-resistant prostate cancer. Cancer, 118: 63–71. doi: 10.1002/cncr.26204
Clinical trial identifiers: CA180-086; NCT00439270.
- Issue published online: 4 MAR 2011
- Article first published online: 4 MAR 2011
- Manuscript Accepted: 28 MAR 2011
- Manuscript Revised: 25 MAR 2011
- Manuscript Received: 6 JAN 2011
- prostate cancer;
To determine the potential efficacy of targeting both the tumor and bone microenvironment in patients with castration-resistant prostate cancer (PC), the authors conducted a phase 1-2 trial combining docetaxel with dasatinib, an oral SRC inhibitor.
In phase 1, 16 men received dasatinib 50 to 120 mg once daily and docetaxel 60 to 75 mg/m2 every 21 days. In phase 2, 30 additional men received dasatinib 100 mg once daily/docetaxel 75 mg/m2 every 21 days. Efficacy endpoints included changes in prostate-specific antigen (PSA), measurable disease, bone scans, and markers of bone metabolism. Safety and pharmacokinetics were also studied.
Combination dasatinib and docetaxel therapy was generally well tolerated. Thirteen of 46 patients (28%) had a grade 3-4 toxicity. Drug-drug interactions and a maximum tolerated dose were not identified. Durable 50% PSA declines occurred in 26 of 46 patients (57%). Of 30 patients with measurable disease, 18 (60%) had a partial response. Fourteen patients (30%) had disappearance of a lesion on bone scan. In bone marker assessments, 33 of 38 (87%) and 26 of 34 (76%) had decreases in urinary N-telopeptide or bone-specific alkaline phosphatase levels, respectively. Twenty-eight patients (61%) received single-agent dasatinib after docetaxel discontinuation and had stabilization of disease for an additional 1 to 12 months.
The high objective response rate and favorable toxicity profile are promising and justify randomized studies of docetaxel and dasatinib in castration-resistant PC. Parallel declines in levels of PSA and bone markers are consistent with cotargeting of epithelial and bone compartments of the cancer. Treatment with single-agent dasatinib following docetaxel cessation warrants further study. Cancer 2012;. © 2011 American Cancer Society.