Literature DB >> 24906049

Is there an antiandrogen withdrawal syndrome with enzalutamide?

Alejo Rodriguez-Vida1, Diletta Bianchini, Mieke Van Hemelrijck, Simon Hughes, Zafar Malik, Thomas Powles, Amit Bahl, Sarah Rudman, Heather Payne, Johann de Bono, Simon Chowdhury.   

Abstract

OBJECTIVE: To examine prostate-specific antigen (PSA) levels after enzalutamide discontinuation to assess whether an antiandrogen withdrawal syndrome (AAWS) exists with enzalutamide.
METHODS: We retrospectively identified 30 consecutive patients with metastatic prostate cancer who were treated with enzalutamide after docetaxel. Post-discontinuation PSA results were available for all patients and were determined at 2-weekly intervals until starting further anticancer systemic therapy. PSA withdrawal response was defined as a PSA decline by ≥50% from the last on-treatment PSA, with a confirmed decrease ≥3 weeks later. Patient characteristics were evaluated in relation to the AAWS using univariate logistic regression analysis.
RESULTS: The median (range) patient age was 70.5 (56-86) years and the median (range) follow-up was 9.0 (0.5-16) months. The most common metastatic sites were the bone (86.7%) and lymph nodes (66.7%). Most patients (70%) had previously received abiraterone and 12 patients (40%) had also received cabazitaxel. The median (range) treatment duration with enzalutamide was 3.68 (1.12-21.39) months. PSA levels after enzalutamide withdrawal were monitored for a median (range) time of 35 (10-120) days. Only one patient (3.3%) had a confirmed PSA response ≥50% after enzalutamide discontinuation. One patient (3.3%) had a confirmed PSA response of between 30 and 50% and another patient (3.3%) had an unconfirmed PSA response of between 30 and 50%. The median overall survival was 15.5 months (95% CI 8.1-24.7). None of the factors analysed in the univariate analysis were significant predictors of PSA decline after enzalutamide discontinuation.
CONCLUSIONS: This retrospective study provides the first evidence that enzalutamide may have an AAWS in a minority of patients with metastatic castration-resistant prostate cancer. Further studies are needed to confirm the existence of an enzalutamide AAWS and to assess its relevance in prostate cancer management.
© 2014 The Authors. BJU International © 2014 BJU International.

Entities:  

Keywords:  androgen receptor gene F876L mutation; androgen receptor targeting; antiandrogen withdrawal syndrome; castration-resistant prostate cancer; enzalutamide; hormone therapy

Mesh:

Substances:

Year:  2014        PMID: 24906049     DOI: 10.1111/bju.12826

Source DB:  PubMed          Journal:  BJU Int        ISSN: 1464-4096            Impact factor:   5.588


  14 in total

Review 1.  An update on enzalutamide in the treatment of prostate cancer.

Authors:  Axel S Merseburger; Gabriel P Haas; Christoph-A von Klot
Journal:  Ther Adv Urol       Date:  2015-02

2.  Prostate cancer: an enzalutamide antiandrogen withdrawal syndrome.

Authors:  Robert Phillips
Journal:  Nat Rev Urol       Date:  2014-06-24       Impact factor: 14.432

Review 3.  Androgen receptor aberrations in the era of abiraterone and enzalutamide.

Authors:  Florian Jentzmik; Anca Azoitei; Friedemann Zengerling; Ilija Damjanoski; Marcus V Cronauer
Journal:  World J Urol       Date:  2015-06-23       Impact factor: 4.226

Review 4.  Mechanisms of Therapeutic Resistance in Prostate Cancer.

Authors:  Mary Nakazawa; Channing Paller; Natasha Kyprianou
Journal:  Curr Oncol Rep       Date:  2017-02       Impact factor: 5.075

Review 5.  Enzalutamide: a review of its use in chemotherapy-naïve metastatic castration-resistant prostate cancer.

Authors:  Gillian M Keating
Journal:  Drugs Aging       Date:  2015-03       Impact factor: 3.923

6.  Comprehensive Analysis of AR Alterations in Circulating Tumor DNA from Patients with Advanced Prostate Cancer.

Authors:  Elisa M Ledet; Michael B Lilly; Guru Sonpavde; Edwin Lin; Roberto H Nussenzveig; Pedro C Barata; Mark Yandell; Rebecca J Nagy; Lesli Kiedrowski; Neeraj Agarwal; Oliver Sartor
Journal:  Oncologist       Date:  2019-11-11

Review 7.  Targeting the adaptive molecular landscape of castration-resistant prostate cancer.

Authors:  Alexander W Wyatt; Martin E Gleave
Journal:  EMBO Mol Med       Date:  2015-07       Impact factor: 12.137

Review 8.  Enzalutamide for the treatment of metastatic castration-resistant prostate cancer.

Authors:  Alejo Rodriguez-Vida; Myria Galazi; Sarah Rudman; Simon Chowdhury; Cora N Sternberg
Journal:  Drug Des Devel Ther       Date:  2015-06-29       Impact factor: 4.162

9.  Comprehensive Analysis of AR Alterations in Circulating Tumor DNA from Patients with Advanced Prostate Cancer.

Authors:  Elisa M Ledet; Michael B Lilly; Guru Sonpavde; Edwin Lin; Roberto H Nussenzveig; Pedro C Barata; Mark Yandell; Rebecca J Nagy; Lesli Kiedrowski; Neeraj Agarwal; Oliver Sartor
Journal:  Oncologist       Date:  2019-11-11

Review 10.  Advanced prostate cancer - patient survival and potential impact of enzalutamide and other emerging therapies.

Authors:  Nihar K Patel; Antoine Finianos; Kristen D Whitaker; Jeanny B Aragon-Ching
Journal:  Ther Clin Risk Manag       Date:  2014-08-16       Impact factor: 2.423

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