title: Feasibility study of a randomized controlled trial comparing docetaxel chemotherapy and androgen deprivation therapy with sequential prostatic biopsies from patients with advanced non-castration-resistant prostate cancer.
abstract: OBJECTIVE
  Sequential tissue biopsies taken during clinical trials of novel systemic anticancer therapies for advanced prostate cancer (PCa) may aid pharmacodynamic evaluation and biomarker discovery. We conducted a single institution phase-II open-labeled randomized study to assess the safety, tolerability, and early efficacy of docetaxel chemotherapy plus androgen deprivation therapy (ADT) vs. ADT alone for patients with advanced non-castration-resistant PCa with sequential prostatic biopsies.
  
  
  METHODS
  We randomized 30 patients with newly diagnosed high-grade locally advanced or metastatic (cT3-4/N0-1/M0-1) PCa to receive ADT with (n = 15) or without (n = 15) docetaxel. Transrectal ultrasound-guided prostatic biopsies were taken at randomization and ~22 weeks after treatment initiation. Primary end point: biochemical response rate. Secondary end points: time to progression and tumor profiling.
  
  
  RESULTS
  Both treatments appear to be well tolerated, and there was no difference in mean nadir prostate-specific antigen and time to prostate-specific antigen relapse between treatment arms (P>0.05). No adverse effects of pre- and post-treatment prostatic biopsies were observed. The study was neither designed nor sufficiently powered to demonstrate statistically significant differences in oncological outcomes or safety profiles between the 2 treatment arms.
  
  
  CONCLUSIONS
  Despite the lack of statistical power, our study suggests that docetaxel and ADT in combination may be well tolerated with apparently similar short-term efficacy compared with ADT alone for high-grade locally advanced or metastatic non-castration-resistant PCa, Sequential prostatic biopsies may provide tissue for tumor profiling to yield mechanistic or prognostic insights relating to novel systemic anticancer therapies.
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, UK. Electronic address: p.rajan@beatson.gla.ac.uk.
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Rajan
authors.affiliation: Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Frew
authors.affiliation: Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Wilson
authors.affiliation: Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Ashraf S T
authors.initials: AS
authors.lastname: Azzabi
authors.affiliation: Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Rhona M
authors.initials: RM
authors.lastname: McMenemin
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Stockley
authors.affiliation: Newcastle Urology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Naeem A
authors.initials: NA
authors.lastname: Soomro
authors.affiliation: Newcastle Urology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Garrett
authors.initials: G
authors.lastname: Durkan
authors.affiliation: Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Pedley
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, UK; Cancer Research UK Beatson Institute, Bearsden, UK. Electronic address: h.leung@beatson.gla.ac.uk.
authors.forename: Hing Y
authors.initials: HY
authors.lastname: Leung
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D001706:Biopsy; D000077143:Docetaxel; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000726:Androgen Antagonists; D043823:Taxoids; D000077143:Docetaxel
keywords: Androgen deprivation therapy; Docetaxel; Prostate cancer; Prostatic biopsy