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

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.

• Authors: 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
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 144 Pg. 302-309 (02 2021) ISSN: 1879-0852 [Electronic] England
• PMID: 33383350 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• AR protein, human
• Androgens
• Receptors, Androgen
• Testosterone

Topics

• Adult
• Aged
• Aged, 80 and over
• Androgens (therapeutic use)
• Drug Resistance, Neoplasm (drug effects)
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Prognosis
• Prostatic Neoplasms, Castration-Resistant (drug therapy, metabolism, pathology)
• Receptors, Androgen (chemistry)
• Survival Rate
• Testosterone (therapeutic use)