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Is there an anti-androgen withdrawal syndrome for enzalutamide?

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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.

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Conflict of interest

All authors are involved in the treatment of prostate cancer with the substance enzalutamide and other hormonal and non-hormonal substances. All authors were directly or indirectly involved in the administration of enzalutamide in the AFFIRM Trial and/or the MDV3100 expanded access program. The manuscript was not motivated nor funded by any external sources/companies, and the authors have no conflicts of interest to declare.

Ethical standard

Ethics board approval was obtained for this retrospective observational study. The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Data were anonymized prior to analysis or protocoled data transfer. No additional data were created nor used aside from retrospective evaluation of our database.

Author information

Authors and Affiliations

  1. Department of Urology and Urologic Oncology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    Christoph A. J. von Klot, Mario W. Kramer, Alena Böker, Thomas R. W. Herrmann, Inga Peters, Markus A. Kuczyk & Axel S. Merseburger

  2. Urologische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany

    Jürgen E. Gschwend, Margitta Retz & Sebastian C. Schmid

  3. Department of Urology, University of Tuebingen, Tübingen, Germany

    Arnulf Stenzl, Christian Schwentner & Tilmann Todenhöfer

  4. Department of Urology, Saarland University, Homburg, Germany

    Michael Stöckle, Carsten-Henning Ohlmann & Ines Azone

  5. Department of Urology, University of Frankfurt am Main, Frankfurt am Main, Germany

    René Mager, Georg Bartsch & Axel Haferkamp

  6. Department of Urology, RWTH University, Aachen, Germany

    Axel Heidenreich & Charlotte Piper

  7. Department of Statistics, TU Dortmund University, Dortmund, Germany

    Uwe Ligges

Authors
  1. Christoph A. J. von Klot
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  2. Mario W. Kramer
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  5. Inga Peters
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  6. Markus A. Kuczyk
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  7. Uwe Ligges
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  8. Jürgen E. Gschwend
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  9. Margitta Retz
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  11. Arnulf Stenzl
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  13. Tilmann Todenhöfer
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  14. Michael Stöckle
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  15. Carsten-Henning Ohlmann
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  16. Ines Azone
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  17. René Mager
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  18. Georg Bartsch
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  19. Axel Haferkamp
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  20. Axel Heidenreich
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  21. Charlotte Piper
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  22. Axel S. Merseburger
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Corresponding author

Correspondence to Axel S. Merseburger.

Additional information

For the German Working Group on Castration Resistant Prostate Cancer (GWG-CRPC).

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von Klot, C.A.J., Kramer, M.W., Böker, A. et al. Is there an anti-androgen withdrawal syndrome for enzalutamide?. World J Urol 32, 1171–1176 (2014). https://doi.org/10.1007/s00345-014-1288-3

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  • DOI: https://doi.org/10.1007/s00345-014-1288-3

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