TY - JOUR
T1 - Bipolar androgen therapy sensitizes castration-resistant prostate cancer to subsequent androgen receptor ablative therapy
AU - Sena, Laura A.
AU - Wang, Hao
AU - Lim ScM, Su J.
AU - Rifkind, Irina
AU - Ngomba, Nduku
AU - Isaacs, John T.
AU - Luo, Jun
AU - Pratz, Caroline
AU - Sinibaldi, Victoria
AU - Carducci, Michael A.
AU - Paller, Channing J.
AU - Eisenberger, Mario
AU - Markowski, Mark C.
AU - Antonarakis, Emmanuel
AU - Denmeade, Samuel R.
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2021/2
Y1 - 2021/2
N2 - 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
AB - 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
KW - Bipolar androgen therapy
KW - Castration-resistant prostate cancer
KW - RESTORE trial
KW - Testosterone
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U2 - 10.1016/j.ejca.2020.11.043
DO - 10.1016/j.ejca.2020.11.043
M3 - Article
C2 - 33383350
AN - SCOPUS:85098659531
SN - 0959-8049
VL - 144
SP - 302
EP - 309
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -