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Dasatinib and docetaxel combination treatment for patients with castration-resistant progressive prostate cancer: A phase I/II study (CA180086).

Publication ,  Journal Article
Araujo, J; Armstrong, AJ; Braud, EL; Posadas, E; Lonberg, M; Gallick, GE; Trudel, GC; Paliwal, P; Agrawal, S; Logothetis, CJ
Published in: J Clin Oncol
May 20, 2009

5061 Background: Dasatinib, a potent inhibitor of SRC family kinases, inhibits in vitro prostate cancer cell proliferation and migration. Consistent with those findings are the clinical observations that osteoclast activity and bone turnover are downregulated in patients treated with dasatinib. We report promising preliminary results of dasatinib in combination with docetaxel (D) for treatment of metastatic castration-resistant prostate cancer (CRPC). METHODS: Male pts with progressive CRPC and castrate levels of testosterone (≤50 ng/dL) requiring chemotherapy were enrolled. Escalating doses of dasatinib (50-120 mg QD) and D (60-75 mg/m(2) Q 21 days) were evaluated (n = 16) followed by enrollment of 30 pts at the phase 2-selected dose (100 mg dasatinib QD + D at 75 mg/m(2) Q 21 days). Continuation of bisphosphonates was permitted; anti-androgens were discontinued. Primary endpoint (Ph. 2) was to determine drug-drug interactions. Secondary endpoints were: changes in PSA, bone scans and tumor size, bone metabolism [urinary N-telopeptide (uNTX) and bone alkaline phosphatase (BAP)] and PK. RESULTS: 46 pts were treated with 28 pts still on therapy. Median treatment duration (n = 18, pts off study) was 4.2 months (0.13-9.63). Preliminary analysis showed no interaction between dasatinib and D. PSA response was seen in 13/32 (41%) pts, clinical benefit (PR + SD) for RECIST-evaluable pts was 21/21, [7 PR, 5 uPR and 4 SD (at ≥21 wks) and 5 SD at ≥6 wk)]. Of 31 pts with bone scans, 30 patients had a best response of either improved (32%) or stable (65%) at ≥6 weeks. For pts with measurable bone markers levels, 12/26 (46%) had a ≥35% decrease in uNTX and 17/24 (71%) had a decrease in BAP from baseline. 6 of 42 pts experienced ≥ grade 3 adverse events (AEs), including fatigue, myelosuppression and pleural effusion (n = 1). Most common grade 1/2 AEs were fatigue, dysgeusia, GI, and skin disorders. CONCLUSIONS: Dasatinib and D at doses up to 120 mg QD and 75 mg/m(2) are safe with manageable toxicities and no drug-drug interactions. These data confirm the antitumor and antiosteoclast activity of dasatinib in combination with D and serve as the basis for the ongoing phase III study of this combination. [Table: see text].

Duke Scholars

Published In

J Clin Oncol

EISSN

1527-7755

Publication Date

May 20, 2009

Volume

27

Issue

15_suppl

Start / End Page

5061

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

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Araujo, J., Armstrong, A. J., Braud, E. L., Posadas, E., Lonberg, M., Gallick, G. E., … Logothetis, C. J. (2009). Dasatinib and docetaxel combination treatment for patients with castration-resistant progressive prostate cancer: A phase I/II study (CA180086). J Clin Oncol, 27(15_suppl), 5061.
Araujo, J., A. J. Armstrong, E. L. Braud, E. Posadas, M. Lonberg, G. E. Gallick, G. C. Trudel, P. Paliwal, S. Agrawal, and C. J. Logothetis. “Dasatinib and docetaxel combination treatment for patients with castration-resistant progressive prostate cancer: A phase I/II study (CA180086).J Clin Oncol 27, no. 15_suppl (May 20, 2009): 5061.
Araujo J, Armstrong AJ, Braud EL, Posadas E, Lonberg M, Gallick GE, et al. Dasatinib and docetaxel combination treatment for patients with castration-resistant progressive prostate cancer: A phase I/II study (CA180086). J Clin Oncol. 2009 May 20;27(15_suppl):5061.
Araujo J, Armstrong AJ, Braud EL, Posadas E, Lonberg M, Gallick GE, Trudel GC, Paliwal P, Agrawal S, Logothetis CJ. Dasatinib and docetaxel combination treatment for patients with castration-resistant progressive prostate cancer: A phase I/II study (CA180086). J Clin Oncol. 2009 May 20;27(15_suppl):5061.

Published In

J Clin Oncol

EISSN

1527-7755

Publication Date

May 20, 2009

Volume

27

Issue

15_suppl

Start / End Page

5061

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences