title: Factors predicting efficacy and adverse effects of enzalutamide in Japanese patients with castration-resistant prostate cancer: results of retrospective multi-institutional study.
abstract: BACKGROUND
  We aimed to evaluate the factors predicting efficacy and adverse effects of enzalutamide in patients with castration-resistant prostate cancer.
  
  
  METHODS
  We retrospectively evaluated data on 345 patients who had received enzalutamide for castration-resistant prostate cancer in 20 hospitals (Kyoto University Hospital and other satellite hospitals). Cox proportional hazards regression analysis was performed to identify factors predicting prostate-specific antigen (PSA) progression after enzalutamide treatment and logistic regression analysis for those associated with development of adverse effects.
  
  
  RESULTS
  PSA titers decreased by >50 % in 197 patients (57 %). The median PSA progression free survival was 163 days. Gleason score >8 (HR 2.078, 95 % CI 1.37-3.153, P = 0.00058), performance status ≥1 (HR 2.292, 95 % CI 1.463-3.592, P = 0.000296), presence of bone metastasis (HR 1.774, 95 % CI 1.019-3.090, P = 0.0429), visceral metastasis (HR 2.127, 95 % CI 1.215-3.722, P = 0.00823), previous steroid treatment (HR 1.780, 95 % CI 1.207-2.626, P = 0.00361) and docetaxel treatment (HR 1.602, 95 % CI 1.051-2.442, P = 0.0284) significantly predicted the efficacy of enzalutamide. Adverse effects, including fatigue or appetite loss, occurred in 169 patients (49 %), 48 (18 %) of whom stopped enzalutamide. Age >75 years (HR 1.980, 95 % CI 1.270-3.09, P = 0.00246) and lower enzalutamide dose (HR 0.437, 95 % CI 0.255-1.270, P = 0.00249) were significantly associated with development of adverse effects.
  
  
  CONCLUSIONS
  Enzalutamide treatment is effective in patients with castration-resistant prostate cancer with low Gleason scores, good performance status, without bone or visceral metastasis and no prior steroid or docetaxel treatment. Lower doses of enzalutamide decrease the incidence of adverse effects, especially in older patients.
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Terada
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Akamatsu
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Negoro
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Toshinari
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Matsui
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kamba
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. ogawao@kuhp.kyoto-u.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001549:Benzamides; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary; D018450:Disease Progression; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000032:analysis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; D017430:Prostate-Specific Antigen
keywords: Adverse effect; Efficacy; Enzalutamide; Predicting factors; Prostate cancer