Development of enzalutamide for metastatic castration‐resistant prostate cancer

Abstract

Prostate cancer is the most prevalent cancer among men in the Western world and a leading cause of cancer-related death among men. Within 5 years of initial diagnosis, approximately 10-20% of men will progress to metastatic castration-resistant prostate cancer (mCRPC). Often characterized by increased prostate-specific antigen and androgen receptor (AR) activity despite castrate levels of testosterone, mCRPC has a poor prognosis and causes significant deterioration in quality of life. Enzalutamide is an AR inhibitor approved to treat mCRPC in both post- and pre-chemotherapy settings on the basis of results from two phase III randomized, placebo-controlled trials, AFFIRM and PREVAIL, respectively. Enzalutamide significantly prolonged overall survival (hazard ratio (HR), AFFIRM 0.63, 95% confidence interval (CI) 0.53-0.75, P < 0.001; PREVAIL 0.71, 95% CI 0.60-0.84, P < 0.001) and radiographic progression (HR, AFFIRM 0.40, 95% CI 0.35-0.47, P < 0.001; PREVAIL 0.19, 95% CI 0.15-0.23, P < 0.001), and significantly improved quality of life. With an acceptable safety profile, enzalutamide is one of several emerging alternative options for men with mCRPC. Studies are ongoing to explore potential benefits of enzalutamide in earlier stages of prostate cancer and in breast cancer.

Statin use and survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide after docetaxel failure: the international retrospective observational STABEN study

“…Abiraterone works by inhibiting residual adrenal and intra-tumoral androgen synthesis via CYP17A blockade [ 6 ], while enzalutamide acts by inhibiting binding of testosterone to the androgen receptor (AR) as well as by blocking androgen-mediated change and nuclear translocation of AR [ 7 ]. In one small retrospective study, statin use was significantly associated with longer OS and early PSA declines in men who received abiraterone [ 8 ].…”

New horizons in the management of castrate-resistant prostate cancer

“…Also Xtandi lacks the partial AR agonist activity that occurs with bicalutamide resistance. 14 Dosing and administration: the drug is administered in pill form through the oral route. The dose is 160 mg (four pills).…”

Enzalutamide alleviates anxiety and depression as well as improves quality of life compared to bicalutamide in metastatic castration-resistant prostate cancer patients: a cohort study

“…Prostate cancer is the second most frequently diagnosed cancer and the fifth leading cause of cancer death in men all around the world, with approximately 1,600,000 newly diagnosed cases and 366,000 prostate cancer-related deaths each year (1)(2)(3)(4)(5)(6). Metastatic castration-resistant prostate cancer (mCRPC), the advanced stage of prostate cancer, happens in about 10-20% prostate cancer patients within 5 years after initial diagnosis (5,(7)(8)(9).…”

“…Prostate cancer is the second most frequently diagnosed cancer and the fifth leading cause of cancer death in men all around the world, with approximately 1,600,000 newly diagnosed cases and 366,000 prostate cancer-related deaths each year (1)(2)(3)(4)(5)(6). Metastatic castration-resistant prostate cancer (mCRPC), the advanced stage of prostate cancer, happens in about 10-20% prostate cancer patients within 5 years after initial diagnosis (5,(7)(8)(9). Recently, improved survival in mCRPC patients has been achieved partly owing to the application of common therapeutic agents (such as bicalutamide), whereas there are still a large portion of patients complicated with psychological disorders including anxiety and depression due to the fast disease progression, intolerable clinical symptoms or other severe complications, which directly decrease their quality of life (QoL) and indirectly cause poor prognosis (10)(11)(12)(13).…”