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
Original language | English (US) |
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Pages (from-to) | 302-309 |
Number of pages | 8 |
Journal | European Journal of Cancer |
Volume | 144 |
DOIs | |
State | Published - Feb 1 2021 |
Externally published | Yes |
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