Bipolar androgen therapy sensitizes castration-resistant prostate cancer to subsequent androgen receptor ablative therapy

Laura A. Sena, Hao Wang, Su J. Lim ScM, Irina Rifkind, Nduku Ngomba, John T. Isaacs, Jun Luo, Caroline Pratz, Victoria Sinibaldi, Michael A. Carducci, Channing J. Paller, Mario A. Eisenberger, Mark C. Markowski, Emmanuel S. Antonarakis, Samuel R. Denmeade

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Cyclical, high-dose testosterone administration, termed bipolar androgen therapy (BAT), can induce clinical responses and restore sensitivity to androgen signalling inhibition in patients with previously treated castration-resistant prostate cancer (PCa) (CRPC). This trial evaluated whether BAT is a safe and effective first-line hormonal therapy for patients with CRPC. Patients and Methods: In cohort C of this single-centre, open-label, phase II, multi-cohort trial (RE-sensitizing with Supraphysiologic Testosterone to Overcome REsistance study), 29 patients with CRPC received first-line hormonal therapy with 400 mg of testosterone cypionate intramuscularly every 28 days concurrent with a luteinising hormone-releasing hormone agonist/antagonist. The primary end-point of the study was the PSA50 response rate to BAT treatment. Results: After treatment with BAT, four of 29 patients (14%; 95% confidence interval [CI]: 4–32%) experienced a PSA50 response. The median radiographic progression-free survival to BAT was 8.5 months (95% CI: 6.9–15.1) for patients with metastatic CRPC. After progression on BAT, 17 of 18 patients (94%; 95% CI: 73–100%) achieved a PSA50 response and 15 of 18 patients (83%; 95% CI: 59–96) achieved a PSA90 response on abiraterone or enzalutamide. Twelve of 15 patients (80%; 95% CI: 52–96) with metastatic CRPC remain on abiraterone or enzalutamide with a median duration of follow-up of 11.2 months. Conclusion: As first-line hormonal treatment for CRPC, BAT was well tolerated and resulted in prolonged disease stabilisation. After progression on BAT, patients had favourable responses to second-generation androgen receptor–targeted therapy. Trial Registration: ClinicalTrials.gov NCT02090114

Original languageEnglish (US)
Pages (from-to)302-309
Number of pages8
JournalEuropean Journal of Cancer
Volume144
DOIs
StatePublished - Feb 1 2021
Externally publishedYes

Bibliographical note

Funding Information:
This project was supported by National Institutes of Health , USA (NIH) grants P30CA006973 ( Johns Hopkins , USA), 2T32CA009071 (to L.A.S.), and 1R01CA184012-01 (to S.R.D.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

  • Bipolar androgen therapy
  • Castration-resistant prostate cancer
  • RESTORE trial
  • Testosterone

PubMed: MeSH publication types

  • Clinical Trial, Phase II
  • Journal Article
  • Multicenter Study
  • Research Support, N.I.H., Extramural

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