A phase I study of testosterone in patients (pts) with early castrate resistant prostate cancer (CRPC)

Abstract

15584 Background: Transition to the castrate resistant state may be due, in part, to the development of a more sensitive and promiscuous androgen receptor (AR) pathway. Androgen therapy of CRPC leads to growth arrest and tumor shrinkage in preclinical models. Historical studies of exogenous testosterone in pts is limited. This study was designed to determine toxicity of a transdermal testosterone therapy (Androderm [A]) in early CRPC. Methods: Pts with progressive PSA increases following androgen ablation and antiandrogen therapy with minimal or no bone metastases (Bone Scan Index of < 1.4%) and no visceral metastases were eligible. Pts were randomized to treatment with 2.5, 5.0, or 7.5mg/day of A and LHRH agonist treatment was maintained. Toxicity was evaluated every 2 weeks and all subjects underwent laboratory, quality of life (UCLA Prostate Cancer Index), and hand grip strength testing at baseline and week 6. Treatment was discontinued for severe toxicity, radiologic progression, or a 3-fold increase in PSA. Results: To date fourteen men were enrolled. Median baseline PSA was 10.9ng/mL (Range:5.3–63.6). Eight pts had no radiologic evidence of disease. Median on therapy testosterone levels (ng/dL) were 216 (n=4), 308 (n=5), 325 (n=5) for 2.5, 5.0, 7.5mg/day dose levels, respectively. Toxicities included grade 2 rash (n=1, dose 7.5), grade 2 hypertension (n=1, dose 7.5), grade 2 hypoglycemia (n=1, dose 5), and grade 2 anorexia (n=1, dose 5). In 29% of pts (n=4), there was a decrease in PSA (max decrease = 43%) from baseline lasting from 4 - 36 weeks; two sustained an initial rise before PSA decline. All other subjects required discontinuation of therapy due to PSA increase and/or radiological progression within 2–13 weeks; none of these patients sustained symptomatic progression of disease and PSA decreased in 8/11 pts with available data after therapy discontinuation. In this small sample, there were no significant differences between baseline and 6-week QOL and hand-grip scores. Conclusion: Testosterone treatment in early CRPC is feasible and safe, although use of PSA to assess anti-tumor effects is difficult. Further evaluation would require a randomized trial to evaluate time to progression and QOL endpoints. No significant financial relationships to disclose.