title: Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study.
abstract: BACKGROUND
  The androgen receptor inhibitor enzalutamide is approved for the treatment of metastatic castration-resistant prostate cancer that has progressed on docetaxel. Our aim was to assess the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer.
  
  
  METHODS
  This trial is an ongoing open-label, single-arm, phase 2 study, done across 12 European sites. Men aged over 18 years, with hormone-naive prostate cancer for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen (PSA) of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide 160 mg/day. The primary outcome was the proportion of patients with an 80% or greater decline in PSA at week 25. All analyses included all patients who had received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT01302041.
  
  
  RESULTS
  67 men were enrolled into the study. 62 patients (92.5%, 95% CI 86.2-98.8) had a decline in PSA of 80% or greater at week 25. The most commonly reported treatment-emergent adverse events up to week 25 were gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12), all of which were of mild to moderate severity. Nine patients had a treatment-emergent adverse event of grade 3 or higher, most of which were reported in one patient each, except for pneumonia (grade 3, two patients) and hypertension (grade 3, four patients). Five patients reported serious adverse events, none of which were deemed to be treatment related.
  
  
  CONCLUSIONS
  Our findings suggest that enzalutamide monotherapy in men with hormone-naive prostate cancer of varying severity provides a level of disease suppression, and was generally well tolerated. These findings provide a rationale for further investigation of clinical response and outcomes with enzalutamide in non-castrate men with prostate cancer.
authors.affiliation: Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium. Electronic address: bertrand.tombal@uclouvain.be.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tombal
authors.affiliation: Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Borre
authors.affiliation: Herlev Hospital, Herlev, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Rathenborg
authors.affiliation: AZ Groeninge Kortrijk, Kortrijk, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Werbrouck
authors.affiliation: UZ Leuven, Leuven, Belgium.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Van Poppel
authors.affiliation: Klinik und Poliklinik für Urologie, RWTH University Aachen, Aachen, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Heidenreich
authors.affiliation: Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Iversen
authors.affiliation: UZ Brussel, Brussels, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Braeckman
authors.affiliation: Univerzita Karlova v Praze, Prague, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Heracek
authors.affiliation: Astellas Pharma Global Development, Leiden, Netherlands.
authors.forename: Edwina
authors.initials: E
authors.lastname: Baskin-Bey
authors.affiliation: Astellas Pharma Global Development, Leiden, Netherlands.
authors.forename: Taoufik
authors.initials: T
authors.lastname: Ouatas
authors.affiliation: Astellas Pharma Global Development, Northbrook, IL, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Perabo
authors.affiliation: Astellas Pharma Global Development, Leiden, Netherlands.
authors.forename: De
authors.initials: D
authors.lastname: Phung
authors.affiliation: Medivation Inc, San Francisco, CA, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hirmand
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, MA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; D017430:Prostate-Specific Antigen