Endocrine Abstracts (2016) 42 OC12 | DOI: 10.1530/endoabs.42.OC12

Rapid cycling high dose testosterone (Bipolar Androgen Therapy) as therapy for men with metastatic castrate-resistant prostate cancer (mCRPC)

Samuel R. Denmeade, Emmanuel Antonarakis, Channing Paller, Hao Wang, Ben Teply, Charles Drake, Michael Carducci, Jun Luo & Mario Eisenberger


The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore MD, USA


Prostate cancer (PC) becomes resistant to chronic castration via an adaptive increase in androgen receptor (AR) axis activity. AR overexpression, however, is a liability that can be exploited therapeutically through rapid cycling between high supraphysiologic and low castrate levels of serum testosterone (T), (Bipolar Androgen Therapy (BAT)). In a pilot study, 14 men with CRPC treated with BAT showed a 50% PSA and objective response. A larger study was initiated in which asymptomatic men with CRPC and progression on abiraterone (A) and/or enzalutamide (E) (30/cohort) receive T cypionate 400 mg every 28 days. At BAT progression men are rechallenged with A or E. Co-primary endpoints include PSA response after 3 cycles of BAT and after re-treatment of E or A. To date, 37 have completed ≥3 cycles of BAT: 11/37 (30%) had ≥ 50% PSA decline. 4/17 (23%) had RECIST responses. Post-BAT, 8/25 (32%) had ≥ 50% PSA response to retreatment A or E. Six men were AR-V7+ and all became AR-V7 negative after BAT with 2/6 having PSA response. BAT has generally been well tolerated with no DLT’s thus far. 1 patient had a self-limited increase in pain and 1 had urinary retention, otherwise there were no bone/soft tissue AE’s with BAT to suggest disease flare. This preliminary data demonstrates the safety and activity of BAT in patients with CRPC post-A and/or E with PSA and objective responses, including responses in AR-V7+ men. An ongoing multi-center randomized trial is testing BAT vs E in the post-A CRPC population.

Funding: One-in-Six Foundation, NIH, Department of Defense Prostate Cancer Research Program.

Presenting Author: Samuel R. Denmeade, M.D. Department of Oncology, The Johns Hopkins University School of Medicine, Cancer Research Building 1, 1650 Orleans Street, Baltimore, Maryland, USA. Email: denmesa@jhmi.edu.

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