title: Zoledronic acid improves clinical outcomes in patients with bone metastatic hormone-naïve prostate cancer in a multicenter clinical trial.
abstract: OBJECTIVE
  To assess whether zoledronic acid (ZOL) adds to the effect of combined androgen blockade (CAB) in patients with hormone-naive bone metastatic prostate cancer.
  
  
  METHODS
  Patients were treated with either a combination of CAB (luteinizing hormone-releasing hormone agonist and bicalutamide) and ZOL (CAB-Z group) or CAB-alone (historical control patients, CAB-C group). ZOL was injected intravenously at 4 mg every 4 weeks. One hundred and five and 100 patients among 205 enrolled patients were assigned to the CAB-Z group and CAB-C group, respectively. The time to prostate-specific antigen (PSA) failure in patients in the CAB-Z group was compared to that in the CAB-C group. The primary end-point of the study was the time-to-PSA failure.
  
  
  RESULTS
  PSA and serum N-telopeptide of type I collagen (NTx) levels were examined before treatment and every 3 months after treatment. PSA failure occurred in 42 (40.0%) patients in the CAB-Z group and 48 (48.0%) patients in the CAB-C group. The biochemical recurrence-free rate was significantly lower in patients in the CAB-C group (p=0.004, by log-rank test). The categorical biopsy Gleason score pre-treatment serum NTx and treatment with ZOL were shown to be independent predictors of PSA failure-free survival time (p=0.040, p=0.005 and p=0.026, respectively).
  
  
  CONCLUSIONS
  ZOL given with CAB as initial treatment delays the time-to-PSA failure in patients with hormone-naive bone metastatic prostate cancer.
authors: Department of Urology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan toke@ks.kyorin-u.ac.jp.
authors: Takatsugu
authors: T
authors: Okegawa
authors: National Hospital Organization Disaster Medical Center, Tachikawa, Tokyo, Japan.
authors: Masao
authors: M
authors: Higaki
authors: Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo, Japan.
authors: Tetsuo
authors: T
authors: Matsumoto
authors: Sassa General Hospital, Nishitokyo, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Kase
authors: Kawakita associates General Hospital, Suginami-ku, Tokyo, Japan.
authors: Akihiro
authors: A
authors: Murata
authors: NishiTokyo Central General Hospital, Nishitokyo, Tokyo, Japan.
authors: Kenjiro
authors: K
authors: Noda
authors: Tama-Hokubu Medical Center, Higashimurayama, Tokyo, Japan.
authors: Haruhisa
authors: H
authors: Noda
authors: Akiru Municipal Medical Center, Akiruno, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Asaoka
authors: Tokyo Metropolitan Tama Medical Center, Fuchu, Tokyo, Japan.
authors: Masaya
authors: M
authors: Oshi
authors: Ome Municipal General Hospital, Ome, Tokyo, Japan.
authors: Junzo
authors: J
authors: Tomoishi
authors: Hitotsubashi Hospital, Kodaira, Tokyo, Japan.
authors: Hiroji
authors: H
authors: Uchida
authors: Department of Urology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors: Eiji
authors: E
authors: Higashihara
authors: Department of Urology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors: Kikuo
authors: K
authors: Nutahara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D024042:Collagen Type I / Q000097:blood / Q000652:urine; D004164:Diphosphonates / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood / Q000652:urine; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000473:pathology*; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid; D017430:Prostate-Specific Antigen
keywords: Prostate-specific antigen; bone metastasis; prostate cancer; zoledronic acid