title: Is there an anti-androgen withdrawal syndrome for enzalutamide?
abstract: BACKGROUND
  The anti-androgen withdrawal syndrome (AAWS) can be seen in one-third of patients after discontinuation of first-generation non-steroidal anti-androgen therapy. With the introduction of new agents for anti-androgen therapy as well as alternate mechanisms of action, new therapeutic options before and after docetaxel chemotherapy have arisen (Ohlmann et al. in World J Urol 30(4):495-503, 2012). The question regarding the occurrence of an enzalutamide withdrawal syndrome (EWS) has not been evaluated yet. In this study, we assess prostate-specific antigen (PSA) response after discontinuation of enzalutamide.
  
  
  METHODS
  In total 31 patients with metastatic castration-resistant prostate cancer (mCRPC) underwent an enzalutamide withdrawal and were evaluated. Data were gathered from 6 centres in Germany. Patients with continuous oral administration of enzalutamide with rising serum PSA levels were evaluated, starting from enzalutamide withdrawal until subsequent therapy was initiated, follow-up ended or death of the patient occurred. Statistical evaluation was performed applying one-sided binomial testing using R-statistical software, version 3.0.1.
  
  
  RESULTS
  Mean withdrawal follow-up was 6.5 weeks (range 1-26.1 weeks). None of the 31 patients showed a PSA decline. Mean relative PSA rise over all patients was 73.9 % (range 0.5-440.7 %) with a median of 44.9 %.
  
  
  CONCLUSIONS
  If existent, an AAWS is at least very rare for enzalutamide in patients with mCRPC after taxane-based chemotherapy and does not play a clinical role in this setting. This may be attributed to the different pharmacodynamics of enzalutamide. Longer duration of therapy or a longer withdrawal interval may reveal a rare EWS in the future.
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany, klot.christoph@mh-hannover.de.
authors.forename: Christoph A J
authors.initials: CA
authors.lastname: von Klot
authors.forename: Mario W
authors.initials: MW
authors.lastname: Kramer
authors.forename: Alena
authors.initials: A
authors.lastname: Böker
authors.forename: Thomas R W
authors.initials: TR
authors.lastname: Herrmann
authors.forename: Inga
authors.initials: I
authors.lastname: Peters
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.forename: Uwe
authors.initials: U
authors.lastname: Ligges
authors.forename: Jürgen E
authors.initials: JE
authors.lastname: Gschwend
authors.forename: Margitta
authors.initials: M
authors.lastname: Retz
authors.forename: Sebastian C
authors.initials: SC
authors.lastname: Schmid
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Christian
authors.initials: C
authors.lastname: Schwentner
authors.forename: Tilmann
authors.initials: T
authors.lastname: Todenhöfer
authors.forename: Michael
authors.initials: M
authors.lastname: Stöckle
authors.forename: Carsten-Henning
authors.initials: CH
authors.lastname: Ohlmann
authors.forename: Ines
authors.initials: I
authors.lastname: Azone
authors.forename: René
authors.initials: R
authors.lastname: Mager
authors.forename: Georg
authors.initials: G
authors.lastname: Bartsch
authors.forename: Axel
authors.initials: A
authors.lastname: Haferkamp
authors.forename: Axel
authors.initials: A
authors.lastname: Heidenreich
authors.forename: Charlotte
authors.initials: C
authors.lastname: Piper
authors.forename: Axel S
authors.initials: AS
authors.lastname: Merseburger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects*; D001549:Benzamides; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy*; D012189:Retrospective Studies; D013375:Substance Withdrawal Syndrome / Q000209:etiology*
chemical_list: D000726:Androgen Antagonists; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; D017430:Prostate-Specific Antigen