Hormonal induction followed by rapid hormonal cycling for prostate cancer (PC): the MEN's Cycle

Abstract

4609 Background: Continuous androgen deprivation (AD) is a standard therapy for systemic PC. Rapid cyclic AD and androgen repletion (AR) after a 1 month induction with castration was shown to be feasible. This trial explores a longer induction period followed by rapid cyclic AD and AR in patients (pts) with limited prior hormone exposure. Methods: Eligible pts had a rising PSA after surgery or radiation, or radiographic metastases, and ≤ 6 months of prior hormone exposure. Treatment consisted of a 3 month induction (GnRH analog monthly & bicalutamide x 1 month) followed by monthly cycles of AR (topical testosterone (T) daily x 7 days) and AD (GnRH analog monthly). A PSA of ≤1ng/ml after induction was required to proceed with cycling. PSA and T levels were monitored post ablation (troughs) and post repletion (peaks). The primary endpoint was the proportion of pts with serially declining PSA troughs after 6 cycles. Treatment failures were defined as 3 sequential increases in PSA troughs prior to 6 cycles. Results: 23 pts were enrolled (5 pts: rising PSA only; 18 pts: metastatic disease). The median baseline PSA was 63ng/ml (2.6–546). The median baseline T level was 383ng/dl (181–654). All cycling pts achieved T levels within the normal reference range during AR and castrate troughs during AD. 5 pts (22%) did not achieve a PSA of ≤1ng/ml after induction and did not cycle. 3 pts were inevaluable. Of the 15 evaluable pts who cycled, 6 pts met the primary endpoint and 3 pts are still being evaluated at < 6 cycles. 6 pts were treatment failures (all continued standard AD off study, of whom 5 pts had further PSA declines). No pt progressed radiographically. Common toxicities included grade 1 fatigue and hot flashes. Conclusion: Rapid hormonal cycling using a 3 month induction is feasible, well-tolerated, and successive declines in the PSA troughs can be achieved. Some pts did show evidence of AD resistance within 3 months by not achieving a PSA of ≤1ng/ml after induction. Based on these results, we have designed a phase II clinical trial using rapid hormonal cycling with no induction in combination with docetaxel in pts with limited prior hormone exposure. Support: CCPP, CA05826, Prostate Cancer Foundation No significant financial relationships to disclose.