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Updated: May 28, 2026
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Dasatinib combined with docetaxel for castration-resistant prostate cancer: results from a phase 1-2 study
John C Araujo1, Paul Mathew, Andrew J Armstrong
1The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. johna@mdanderson.org
Background:
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.
Methods:
In phase 1, 16 men received dasatinib 50 to 120 mg once daily and docetaxel 60 to 75 mg/m(2) every 21 days. In phase 2, 30 additional men received dasatinib 100 mg once daily/docetaxel 75 mg/m(2) 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.
Results:
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.
Conclusions:
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.
Insights
This study combined docetaxel with dasatinib in castration-resistant prostate cancer, showing promising response rates and tolerability. Further randomized trials are warranted to confirm efficacy in targeting both tumor and bone environments.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Castration-resistant prostate cancer (PC) presents a therapeutic challenge, necessitating novel strategies.
- Targeting both the primary tumor and the bone microenvironment is a potential approach for improved efficacy.
Purpose of the Study:
- To evaluate the safety and efficacy of combining docetaxel with dasatinib in patients with castration-resistant PC.
- To assess the impact of this combination on prostate-specific antigen (PSA) levels, measurable disease, bone scans, and bone metabolism markers.
Main Methods:
- A phase 1-2 trial was conducted, initially determining dose escalation for dasatinib and docetaxel.
- Phase 2 involved a larger cohort receiving a defined dose of both agents every 21 days.
- Efficacy was measured by PSA decline, objective tumor response, bone scan changes, and bone turnover markers; safety and pharmacokinetics were also assessed.
Main Results:
- The combination therapy was generally well tolerated, with 28% experiencing grade 3-4 toxicity.
- A 50% decline in PSA was observed in 57% of patients, and 60% with measurable disease achieved a partial response.
- Significant decreases in bone turnover markers were noted, and 61% of patients had disease stabilization on single-agent dasatinib after docetaxel cessation.
Conclusions:
- Combination therapy with docetaxel and dasatinib demonstrated a high objective response rate and a favorable toxicity profile in castration-resistant PC.
- The parallel reduction in PSA and bone markers suggests effective cotargeting of the cancer's epithelial and bone compartments.
- Further investigation, including randomized studies and the role of single-agent dasatinib, is warranted.
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