Chapter 21. New Horizons in the Treatment of Proliferative Prostatic Disease

Publisher Summary This chapter discusses the new endocrine as well as non-endocrine pharmacological agents currently under development for the treatment of prostate cancer (PC) and benign prostatic hyperplasia (BPH). Cyproterone acetate (CPA) continues to be the most thoroughly studied antiandrogenic agent and has the approval for use in PC in several countries. Flutamide, the prototype non-steroidal pure androgen receptor (AR) antagonist, also has approval for use in PC. The effects of flutamide on T, 5α-dihydrotestosterone (DHT), and the localization of AR in tissues from BPH patients have been reported. Anandron (RU 23908) is a non-steroidal AR antagonist primarily targeted for use in hormone-responsive PC. The dihydroethisterone derivative WIN 49596 is reported to be an AR antagonist. A direct cytotoxic effect of ketoconazole on PC cells has been suggested. The discovery and development of potent and selective inhibitors of 5α-reductase and “pure” AR antagonists that do not uncouple negative-feedback at the hypothalamic/pituitary demonstrates continuing interest in this therapeutic arena. Luteinizing-hormone releasing hormone (LHRH) agonists are being developed for the treatment of various hormone dependent disorders, including endometriosis, breast cancer, PC, and benign prostatic hyperplasia (BPH). The use of selective alpha-1 adrenergic antagonists for the treatment of urinary retention, associated with BPH, is being investigated. Growth factors must also regulate neoplastic prostatic growth as both normal and malignant prostatic epithelial cells can proliferate in vitro in the absence of androgens. Further research on the prostate should reveal additional new potential approaches and allow clinicians to select specific agents or a combination of agents based on the underlying pathophysiology.