title: Phase II trial of zoledronic acid combined with androgen-deprivation therapy for treatment-naïve prostate cancer with bone metastasis.
abstract: BACKGROUND
  The efficacy of zoledronic acid in patients with treatment-naïve prostate cancer is unclear. We conducted a phase II study to investigate the benefits of combined zoledronic acid and androgen deprivation therapy in treatment-naïve prostate cancer with bone metastasis. The primary endpoint was skeletal-related event-free survival at 24 months.
  
  
  METHODS
  Subjects were treatment-naïve patients with histologically confirmed adenocarcinoma of the prostate and radiological evidence of bone metastasis. Treatment consisted of bicalutamide 80 mg daily, goserelin acetate 10.8 mg every 12 weeks, and zoledronic acid 4 mg every 4 weeks. Zoledronic acid was continued for 24 months.
  
  
  RESULTS
  Of the patients enrolled between July 2008 and April 2010, 52 were included in the analyses. The median age of the patients was 72 years. The median baseline prostate-specific antigen level was 249.4 ng/mL. The median follow-up period was 33.3 months. The 24-month skeletal-related event-free survival rate was 84.4 % (95 % confidence interval 71.2-91.9). The median time to prostate-specific antigen progression was 25.9 months (95 % confidence interval 14.7-36.3). The median overall survival time was not reached. Improvement in pain or maintenance of no pain during the first 12 weeks was observed in 70 % of patients and the extent of bone disease was decreased in 10 % of patients at 12 months. Grade 3 osteonecrosis of the jaw was observed in three patients (5.8 %).
  
  
  CONCLUSIONS
  Zoledronic acid concomitant with androgen deprivation therapy as initial treatment in patients with treatment-naïve prostate cancer with bone metastasis resulted in an encouraging skeletal-related event-free survival rate at 24 months.
authors.affiliation: Department of Urology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan, nozawa06@med.kindai.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nozawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inagaki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagao
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Nishioka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Komura
authors.forename: Atsunobu
authors.initials: A
authors.lastname: Esa
authors.forename: Michio
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Imanishi
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Uekado
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Ogawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kajikawa
authors.forename: Shigeya
authors.initials: S
authors.lastname: Uejima
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Matsuyama
authors.forename: Isao
authors.initials: I
authors.lastname: Hara
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uemura
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage*; D000728:Androgens / Q000378:metabolism; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D017273:Goserelin / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000077211:Zoledronic Acid
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D004164:Diphosphonates; D007093:Imidazoles; D017273:Goserelin; D000077211:Zoledronic Acid; D017430:Prostate-Specific Antigen
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