title: [Efficacy of low dose ketoconazole therapy for Chinese patients with castration resistant prostate cancer].
abstract: OBJECTIVE
  To assess the efficacy of low dose ketoconazole therapy for Chinese patients with castration resistant prostate cancer (CRPC) and explore possible prognosis factors.
  
  
  METHODS
  From August 2006 to August 2011, 71 patients with CRPC were analyzed retrospectively, who received oral ketoconazole 200 mg, three times a day with prednisone 5 mg, twice a day. Prostate specific antigen (PSA) response rate was defined as the percentage of patients with PSA decline ≥ 50% compared to baseline PSA level during low dose ketoconazole therapy. Multivariate Logistic regression analysis and receiver operating characteristic curve were used to assess the prognostic factors and their accuracy.
  
  
  RESULTS
  The mean initial serum PSA level was (205 ± 38) ng/ml for these patients with mean age (69 ± 1) years old. After first androgen deprivation therapy failure, the prostate cancer progressed into castration resistant stage. The baseline PSA was (93 ± 24) ng/ml and the baseline serum testosterone was (0.13 ± 0.02) ng/ml. During the low dose ketoconazole therapy, 31 patients (43.7%) had PSA decrease and 22 cases (31.0%) were effective with PSA decline more than 50%. PSA doubling time and baseline serum testosterone were positive correlation with PSA response rate by multivariate Logistic regression analysis. Patients with PSA doubling time of ≥ 3.0 months had a PSA response rate of 64.3% and the PSA response rate in those with < 3.0 months decreased to 22.8%, hazard rate (HR) = 0.149 (95% confidence interval [CI] 0.029 - 0.766), P = 0.023, area under the curve (AUC) = 0.707. The PSA response rate for patients with baseline serum testosterone ≥ 0.1 and < 0.1 µg/L were 55.6% and 5.7%, respectively, HR = 0.068 (95%CI 0.012 - 0.380), P = 0.002, AUC = 0.749. The common adverse reactions included liver dysfunction (17.9%), renal dysfunction (16.4%), fatigue (11.9%), nausea (6.0%) and anorexia (4.5%) and so on.
  
  
  CONCLUSIONS
  Low dose ketoconazole therapy was a moderate, low toxicity hormonal therapy option for patients with CRPC. PSA doubling time ≥ 3 months and baseline serum testosterone ≥ 0.1 µg/L were predictors of desired effect for low dose ketoconazole therapy.
authors.affiliation: Department of Urology, Shanghai Cancer Center, Fudan University, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Guo-wen
authors.initials: GW
authors.lastname: Lin
authors.forename: Ding-wei
authors.initials: DW
authors.lastname: Ye
authors.forename: Xu-dong
authors.initials: XD
authors.lastname: Yao
authors.forename: Shi-lin
authors.initials: SL
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Dai
authors.forename: Hai-liang
authors.initials: HL
authors.lastname: Zhang
authors.forename: Yi-jun
authors.initials: YJ
authors.lastname: Shen
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yi-ping
authors.initials: YP
authors.lastname: Zhu
authors.forename: Guo-hai
authors.initials: GH
authors.lastname: Shi
authors.forename: Chun-guang
authors.initials: CG
authors.lastname: Ma
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Xiao
authors.forename: Xiao-jian
authors.initials: XJ
authors.lastname: Qin
mesh_terms: D000368:Aged; D002369:Castration; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage* / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D012372:ROC Curve; D012189:Retrospective Studies; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome
chemical_list: D013739:Testosterone; D017430:Prostate-Specific Antigen; D007654:Ketoconazole