title: Once-daily dasatinib: expansion of phase II study evaluating safety and efficacy of dasatinib in patients with metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Oncology, University of Washington, Seattle, Washington 98109, USA. evanyu@u.washington.edu
authors.forename: Evan Y
authors.initials: EY
authors.lastname: Yu
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Gross
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.forename: Stephane
authors.initials: S
authors.lastname: Culine
authors.forename: Gary
authors.initials: G
authors.lastname: Hudes
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Posadas
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Géralyn C
authors.initials: GC
authors.lastname: Trudel
authors.forename: Prashni
authors.initials: P
authors.lastname: Paliwal
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000069439:Dasatinib; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D007987:Gonadotropin-Releasing Hormone; D000069439:Dasatinib