title: An evaluation of intermediate-dose ketoconazole in hormone refractory prostate cancer.
abstract: OBJECTIVE
  The management of hormone refractory prostate cancer remains controversial. Among the options, second-line hormonal therapy is commonly used. We investigated the efficacy of ketoconazole, an inhibitor of testicular and adrenal androgen biosynthesis, for treating patients with advanced hormone refractory prostate cancer.
  
  
  METHODS
  The study comprised 38 patients with progressive disease despite combined androgen blockade. Treatment consisted of intermediate-dose ketoconazole (300mg three times daily) and replacement hydrocortisone. Patients were monitored clinically and with serial psa measurements every 3 months. the principal endpoint was psa response.
  
  
  RESULTS
  Of the 38 patients, 21 (55.3%) showed a decrease in PSA >50% (95% confidence interval 38.3%-71.4%) with a median duration of 6 months (range 3-48 months). A PSA reduction >50% was seen in 21 of 34 patients (61.8%) with established metastases. Thirteen patients (34.2%), all of whom had metastases, exhibited a PSA decrease >80% (95% confidence interval 19.6%-51.4%) with a median duration of 9 months (range 3-48 months). Age, PSA at diagnosis, Gleason score and bone scan result were not significantly associated with response to ketoconazole treatment in univariate or multivariate analyses. For the entire study group, the median time to progression was 5 months (range 0-27 months) and the median survival was 12 months (range 3-48 months). Overall, 12 patients (31.6%) reported toxicity related to intermediate-dose ketoconazole but only 6 patients (15.8%) discontinued therapy due to intolerable side effects.
  
  
  CONCLUSIONS
  It is apparent from this study that a reasonable percentage of patients failing standard hormonal therapy respond favourably to intermediate-dose ketoconazole and that toxicity is mild. In the absence of studies demonstrating better survival with chemotherapy, we believe that a trial of ketoconazole should be considered when progression occurs on hormone therapy.
authors.affiliation: The Midwest Prostate and Urology Health Center, Weiss Memorial Hospital, 4646 North Marine Drive, Chicago, IL 60640, USA. simonmwilkinson@hotmail.com
authors.forename: Simon
authors.initials: S
authors.lastname: Wilkinson
authors.forename: Gerald
authors.initials: G
authors.lastname: Chodak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D017211:Treatment Failure
chemical_list: D000726:Androgen Antagonists; D007654:Ketoconazole