Bipolar androgen therapy (BAT) in men with hormone sensitive (HS) prostate cancer (PC).

Abstract

236 Background: We documented a paradoxical anti-tumor effect when castration-resistant prostate cancer patients were treated with intermittent, high-dose testosterone (i.e. BAT) [PMID: 25568070]. Since the adaptive increase in androgen receptor expression that follows chronic androgen deprivation therapy (ADT) may underlie this effect, we tested whether men with HS PC would also respond to BAT if given following a 6-month ADT lead-in. Methods: Men with asymptomatic HS PC and low metastatic burden (N = 20) (no visceral disease, ≤ 10 bone metastases, no lymph nodes > 5 cm short axis diameter) or non-metastatic biochemically recurrent disease (N = 13) were enrolled. Following 6-months of ADT, those with a PSA < 4 ng/ml went on to receive 2 cycles of BAT. A cycle of BAT was defined as intramuscular testosterone (T) cypionate or enanthate 400 mg on Days (D) 1, 29 and 57 followed by ADT alone D 85-169. ADT was continued throughout the study to allow for rapid cycling from near castrate to supraphysiologic range T following T injections. The primary endpoint was the percent of patients with a PSA < 4 ng/ml after 2 cycles of BAT, with the study designed to reject a null rate of 40% at a one-sided alpha = 0.1. Secondary endpoints included quality of life (QOL) as measured by the SF-36, FACT-P, IIEF and IPSS surveys. Results: Twenty-nine of 33 patients received BAT following the ADT lead-in (1 withdrew consent, 3 had PSA > 4 ng/ml). The primary endpoint was met, with 17/29 men (59%, lower bound 90% confidence interval = 45%) having a PSA < 4 ng/ml after 2 cycles of BAT. Ten patients receiving BAT had RECIST evaluable disease, and 8 (80%) objective responses were observed (4 complete; 4 partial). Three patients progressed per RECIST criteria and 3 had unconfirmed progression on bone scan. Men treated with 6-months of ADT had improved QOL after the first cycle of BAT. The median improvement in SF-36, FACT-P, and IIEF total scores were 3.2 (range, -20 to 48; P = 0.21), 3.5 (range, -30 to 50; P = 0.04), and 10 (range, -4 to 59; P < 0.001) points, respectively. There was no change in total IPSS score (median change 0 [range, -9 to 8; P = 0.87]). Conclusions: BAT demonstrated preliminary efficacy in men with HS PC following 6-months of ADT. BAT may improve QOL in men that have received ADT. Clinical trial information: NCT01750398.