Anti-androgens for the treatment of non-metastatic castrate-resistant prostate cancer

1. A method of treating non-metastatic castration-resistant prostate cancer in a male human comprising administering a therapeutically effective amount of an anti-androgen to a male human in need of such treatment, wherein the anti-androgen is 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide, and wherein the anti-androgen is administered in combination with a gonadotropin-releasing hormone (GnRH) agonist or antagonist, or orchiectomy.

2. The method of claim 1 , wherein the non-metastatic castration-resistant prostate cancer is a high risk non-metastatic castration-resistant prostate cancer.

3. The method of claim 1 , wherein the 4-(3 (4 cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered in combination with the GnRH agonist or antagonist.

4. The method of claim 1 , wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered in combination with the GnRH agonist and the GnRH agonist is leuprolide, buserelin, nafarelin, histrelin, goserelin, or deslorelin.

5. The method of claim 1 , wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered post-orchiectomy.

6. The method of claim 1 , wherein the male human previously received a first-generation anti-androgen, and wherein the first-generation anti-androgen is bicalutamide, flutamide or nilutamide.

7. The method of claim 1 , wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered daily to the male human.

8. The method of claim 1 , wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered orally to the male human.

9. The method of claim 1 , wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered orally to the male human on a continuous daily dosing schedule.

10. The method of claim 1 , wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered orally to the male human at a dose of about 160 mg per day.

11. The method of claim 1 , wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is in a unit dosage form, and wherein the unit dosage form is in the form of a tablet.

12. A method of treating non-metastatic castration-resistant prostate cancer in a male human consisting essentially of administering an anti-androgen to a male human in need of such treatment, wherein the anti-androgen is 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide, and wherein the anti-androgen is administered in combination with a gonadotropin-releasing hormone (GnRH) agonist or antagonist, or orchiectomy.

13. The method of claim 12 , wherein the non-metastatic castration-resistant prostate cancer is a high risk non-metastatic castration-resistant prostate cancer.

14. The method of claim 12 , wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered in combination with the GnRH agonist or antagonist.

15. The method of claim 12 , wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered in combination with the GnRH agonist and the GnRH agonist is leuprolide, buserelin, nafarelin, histrelin, goserelin, or deslorelin.

16. The method of claim 12 , wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered post-orchiectomy.

17. The method of claim 12 , wherein the 4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide is administered orally to the male human at a dose of about 160 mg per day.

18. The method of claim 1 , wherein the male human with the high risk non-metastatic castration-resistant prostate cancer has a prostate-specific antigen doubling time (PSADT) that is less than or equal to 10 months.

19. The method of claim 1 , wherein administration of the anti-androgen provides an increase in the metastasis-free survival of the male human, relative to the mean metastasis-free survival rate of a population of male humans with the non-metastatic castration-resistant prostate cancer, said population having been treated with a placebo.