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, 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
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.
Keywords: Bipolar androgen therapy; Castration-resistant prostate cancer; RESTORE trial; Testosterone.
Conflict of interest statement
Conflict of interest statement E.S.A. reports being a paid consultant/advisor to Janssen, Astellas, Sanofi, Dendreon, Pfizer, Amgen, Lilly, Bayer, AstraZeneca, Bristol-Myers Squibb, Clovis and Merck; reports receiving research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Tokai, Bristol Myers-Squibb, AstraZeneca, Clovis, and Merck and he reports being the co-inventor of an AR-V7 biomarker technology that has been licenced to Qiagen.
Copyright © 2020 Elsevier Ltd. All rights reserved.
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Source: PubMed