title: A phase II clinical trial of neoadjuvant ketoconazole and docetaxel chemotherapy before radical prostatectomy in high risk patients.
abstract: OBJECTIVE
  Patients with high risk prostate cancer (prostate specific antigen greater than 20 ng/ml, Gleason score greater than 7, or clinical stage T2b or greater) have been shown to have a 30% to 40% biochemical recurrence rate after definitive local therapy. Looking for improvement on these outcomes, we conducted a phase II clinical trial examining the combination of ketoconazole and docetaxel in the neoadjuvant setting before radical prostatectomy.
  
  
  METHODS
  A total of 22 patients with clinically localized, high risk prostate cancer were enrolled in the study. For 12 weeks they were treated with neoadjuvant docetaxel and ketoconazole, with dosing based on phase I data. Patients were monitored for tolerance of therapy and dosing adjustments were made for significant toxicities. Radical prostatectomy with extended lymph node dissection was subsequently performed and patients were followed postoperatively for biochemical recurrence.
  
  
  RESULTS
  At a median followup of 18 months 8 patients remained biochemically free of recurrence after surgery alone. An additional 6 patients received salvage therapy and had an undetectable prostate specific antigen. Of the 22 patients 16 experienced National Cancer Institute grade 3 or 4 toxicity at some point during the therapy. However, 16 patients completed all 4 cycles of chemotherapy.
  
  
  CONCLUSIONS
  Neoadjuvant ketoconazole combined with docetaxel has appreciable but acceptable toxicity with 73% of the patients completing all 4 courses of therapy. Of those who underwent radical prostatectomy 36% remained continuously biochemically free of recurrence at a median followup of 18 months.
authors.affiliation: Department of Urology, University of Kansas Hospital, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Womble
authors.forename: Peter J
authors.initials: PJ
authors.lastname: VanVeldhuizen
authors.forename: Alan A
authors.initials: AA
authors.lastname: Nisbet
authors.forename: Greg A
authors.initials: GA
authors.lastname: Reed
authors.forename: J Brantley
authors.initials: JB
authors.lastname: Thrasher
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Holzbeierlein
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D006801:Humans; D007654:Ketoconazole / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011300:Preoperative Care; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery; D012307:Risk Factors; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D007654:Ketoconazole