Is there an anti-androgen withdrawal syndrome for enzalutamide?

Christoph A.J. von Klot, Mario W. Kramer, Alena Böker, Thomas R.W. Herrmann, Inga Peters, Markus A. Kuczyk, Uwe Ligges, Jürgen E. Gschwend, Margitta Retz, Sebastian C. Schmid, Arnulf Stenzl, Christian Schwentner, Tilmann Todenhöfer, Michael Stöckle, Carsten Henning Ohlmann, Ines Azone, René Mager, Georg Bartsch, Axel Haferkamp, Axel HeidenreichCharlotte Piper, Axel S. Merseburger*

*Corresponding author for this work
10 Citations (Scopus)


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.

Original languageEnglish
JournalWorld Journal of Urology
Issue number5
Pages (from-to)1171-1176
Number of pages6
Publication statusPublished - 10.2014

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)


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