title: Oral enzastaurin in prostate cancer: a two-cohort phase II trial in patients with PSA progression in the non-metastatic castrate state and following docetaxel-based chemotherapy for castrate metastatic disease.
abstract: OBJECTIVE
  Enzastaurin is an oral serine/threonine kinase inhibitor of the beta isoform of protein kinase C that may have therapeutic activity in prostate cancer. We explored the efficacy of enzastaurin on two cohorts of patients with prostate cancer progression in the castrate state.
  
  
  METHODS
  A two-cohort phase II trial was conducted, with both groups participating simultaneously. Cohort 1 consisted of patients with non-metastatic castrate prostate-specific antigen progressive disease. Cohort 2 consisted of patients with castrate metastatic disease with progression following docetaxel-based chemotherapy. Patients in both cohorts received 500 mg/day enzastaurin.
  
  
  RESULTS
  Therapy was well tolerated in both cohorts. One complete response was observed in Cohort 1, with limited activity in the majority of patients. In Cohort 2, no objective responses were seen and the median progression-free survival (11 weeks [90% confidence interval: 7.6, 11.7]) did not differ from the historical control.
  
  
  CONCLUSIONS
  Enzastaurin as a single agent has limited activity in castrate progressive prostate cancer. Evaluation in combination with docetaxel is ongoing.
authors.affiliation: Department of Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA. dreicer@ccf.org
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
authors.forename: Jorge
authors.initials: J
authors.lastname: Garcia
authors.forename: Maha
authors.initials: M
authors.lastname: Hussain
authors.forename: Brian
authors.initials: B
authors.lastname: Rini
authors.forename: Nicholas
authors.initials: N
authors.lastname: Vogelzang
authors.forename: Sandy
authors.initials: S
authors.lastname: Srinivas
authors.forename: Bradley
authors.initials: B
authors.lastname: Somer
authors.forename: Yan D
authors.initials: YD
authors.lastname: Zhao
authors.forename: Marek
authors.initials: M
authors.lastname: Kania
authors.forename: Derek
authors.initials: D
authors.lastname: Raghavan
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D018572:Disease-Free Survival; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D017430:Prostate-Specific Antigen; C504878:enzastaurin