Adrenal androgen synthesis inhibitor therapies in castration-resistant prostate cancer

It is well recognized that the vast majority of prostate cancers rely on testosterone for growth. Even after medical or surgical castration, a significant number of men will unfortunately experience disease progression manifested as an increasing prostate-specific antigen (PSA) or objective tumor growth. Left untreated, castration-resistant prostate cancer (CRPC) is uniformly fatal. It causes close to 30,000 deaths annually in the United States, with most men living only 2-4 years from the time castration resistance develops. In recent years, research has shown that despite castration resistance these tumors still retain sensitivity to low levels of circulating testosterone and other androgens. By inhibiting androgen synthesis, targeted adrenal androgen synthesis inhibitors slow the growth of castration-resistant tumors. The major agents in use today include corticosteroids, ketoconazole, aminoglutethimide, estrogens and progestins, as well as the novel CYP17 inhibitors abiraterone acetate, TAK-700 and TOK-001. The following article reviews the clinical data supporting the use of each of these adrenal androgen synthesis inhibitors in advanced prostate cancer, including the dosing, schedules, and common side effects.