Once-daily dasatinib: Expansion of phase II study evaluating safety and efficacy of dasatinib in patients with metastatic castration-resistant prostate cancer

Evan Y. Yu, Christophe Massard, Mitchell E. Gross, Michael A. Carducci, Stephane Culine, Gary Hudes, Edwin M. Posadas, Cora N. Sternberg, George Wilding, Géralyn C. Trudel, Prashni Paliwal, Karim Fizazi

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: To determine the activity and tolerability of 100-mg once-daily (QD) dasatinib in patients with metastatic castration-resistance prostate cancer (CRPC). Dasatinib, an oral Src family kinase inhibitor, has demonstrated both preclinical and clinical activity with twice-daily dosing in patients with metastatic CRPC. Methods: Chemotherapy-naive men with metastatic CRPC and increasing prostate-specific antigen levels were treated with dasatinib 100 mg QD. The primary measurement was a composite lack of disease progression, according to the Prostate Cancer Working Group 2 criteria, determined every 12 weeks during the study. The other analyses included changes in the prostate-specific antigen level, bone lesions, soft tissue disease, and bone turnover markers (urine N-telopeptide and bone alkaline phosphatase). Results: The present trial was designed before the publication of the recent Prostate Cancer Working Group 2 criteria; however, the analyses are presented to conform to the updated guidelines. A total of 48 patients received dasatinib. A lack of disease progression was observed in 21 patients (44%) at week 12 and in 8 (17%) at week 24. Urine N-telopeptide was reduced by <40% from baseline in 22 (51%) of 43 patients, and bone alkaline phosphatase was decreased in 26 (59%) of 44 patients. Dasatinib was well-tolerated, with only 6 patients (13%) with drug-related grade 3-4 adverse events and 3 (6%) with grade 3 adverse events. The most common treatment-related adverse events (<20%) were fatigue, nausea, diarrhea, headache, and anorexia. Conclusions: Dasatinib 100 mg QD has a favorable safety profile and maintains a similar degree of activity as the previously reported twice-daily dosing schedules. These data support additional study of dasatinib 100 mg QD for metastatic CRPC.

Original languageEnglish (US)
Pages (from-to)1166-1171
Number of pages6
JournalUrology
Volume77
Issue number5
DOIs
StatePublished - May 2011

ASJC Scopus subject areas

  • Urology

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