title: Phase II study of imatinib mesylate in patients with prostate cancer with evidence of biochemical relapse after definitive radical retropubic prostatectomy or radiotherapy.
abstract: OBJECTIVE
  Patients with biochemical recurrence of prostate cancer after definitive or salvage local therapy in the absence of metastatic disease represent a group well suited to a novel therapeutic intervention. Imatinib mesylate (Gleevec) is a protein-tyrosine kinase inhibitor that has previously been tested in men with androgen-independent and metastatic prostate cancer. This Phase II study was undertaken to determine the safety and efficacy of imatinib mesylate in men with biochemical relapse of nonmetastatic, androgen-sensitive prostate cancer after local therapy.
  
  
  METHODS
  Twenty-seven patients were treated with imatinib mesylate 400 mg twice daily for up to 12 months. Three patients (11%) completed less than 4 weeks of therapy and were included in the intent-to-treat analysis of the response to therapy.
  
  
  RESULTS
  Of the 27 patients treated, 5 (18.5%) had a stable prostate-specific antigen (PSA) during the course of treatment; 2 patients (7.4%) experienced a partial response. The remaining 20 patients (74.1%) demonstrated PSA progression. The median progression-free survival was 3 months. The proportion of patients achieving a partial PSA response during therapy did not significantly differ from the null rate of 5% (P = 0.394). Seven patients (25.9%) discontinued therapy secondary to grade 1 to 3 toxicities. No irreversible National Institutes of Health Common Toxicity Criteria grade 3 or 4 toxicities occurred. Grade 3 and 4 toxicity included leukopenia (3.7%), serum glutamic-oxaloacetic transaminase (3.7%) and serum glutamic-pyruvic transaminase (3.7%) elevation, and rash (18.5%).
  
  
  CONCLUSIONS
  The results of our study have demonstrated that imatinib mesylate delivered at a dose of 400 mg twice daily is associated with a moderate degree of toxicity and a limited PSA response in this patient population.
authors: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors: Gopal K
authors: GK
authors: Bajaj
authors: Zhe
authors: Z
authors: Zhang
authors: Elizabeth
authors: E
authors: Garrett-Mayer
authors: Renee
authors: R
authors: Drew
authors: Victoria
authors: V
authors: Sinibaldi
authors: Roberto
authors: R
authors: Pili
authors: Samuel R
authors: SR
authors: Denmeade
authors: Michael A
authors: MA
authors: Carducci
authors: Mario A
authors: MA
authors: Eisenberger
authors: Theodore L
authors: TL
authors: DeWeese
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012008:Recurrence; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011505:Protein-Tyrosine Kinases; D017430:Prostate-Specific Antigen