Development of prostate-selective, sustained-release anti-androgen implants for prostate cancer treatment.

Prostate cancer is the most common cancer in men. While active surveillance is now routinely offered to men with early-stage prostate cancer, almost 50% will eventually require definitive therapy, like radiation or prostatectomy, which carry significant genitourinary side effects. Systemic antiandrogen therapy have approved for locally-advanced and metatatic prostate cancer, but their substantial metabolic, sexual, and cardiovascular side effects have precluded its use for early-stage disease or prevention. Localized sustained release of an anti-androgen via a drug-delivering implant could provide long-term, prostate-specific delivery of anti-androgens while avoiding systemic toxicity. Biolen®, is a silicone-based bicalutamide implant with the ability to deliver sustained bicalutamide levels to the prostate for more than 2 years. In IND enabling canine studies, we observed therapeutic intraprostatic levels with minimal systemic exposure and no off-target toxicities. Prostate bicalutamide levels were similar to oral bicalutamide but with nearly 1000-fold lower systemic plasma bicalutamide levels. Implants caused no fibrotic encapsulation, inflammation or local tissue toxicity. A phase I pre-surgical trial in men with localized prostate cancer confirmed high therapeutic prostate levels with very low systemic exposure. These results support exploration of this approach in early-stage prostate cancer, benign prostate hyperplasia, and other settings that would benefit from sustained organ-selective drug delivery.