Anti-androgens for the treatment of non-metastatic castrate-resistant prostate cancer
Described herein are methods of treating non-metastatic castrate-resistant prostate cancer with anti-androgens.
1. A method of treating a male human with non-metastatic castration-resistant prostate cancer, the method comprising administering an anti-androgen at a dose of about 30 mg per day to about 480 mg per day to a male human in need of such treatment, wherein the anti-androgen is:
4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2 fluoro-N-methylbenzamide,
4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide, or
4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide;
wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist.
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 anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide.
4. The method of claim 3 , wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide is administered daily to the male human.
5. The method of claim 3 , wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5, 7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide (ARN-509) is administered orally to the male human at a dose of about 180 mg per day to about 480 mg per day.
6. The method of claim 3 , wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide (ARN-509) is administered orally to the male human at a dose of:
(a) about 30 mg per day;
(b) about 60 mg per day;
(c) about 90 mg per day;
(d) about 120 mg per day; or
(e) about 240 mg per day.
7. The method of claim 3 , wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide is administered orally to the male human on a continuous daily dosage schedule.
8. The method of claim 3 , wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin.
9. The method of claim 1 , 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.
10. The method of claim 9 , wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin.
11. The method of claim 1 , wherein the anti-androgen is 4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide.
12. The method of claim 11 , wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin.
13. The method of claim 1 , wherein the anti-androgen is administered orally to the male human.
14. A method of treating a male human with non-metastatic castration-resistant prostate cancer, the method consisting essentially of administering an anti-androgen at a dose of about 30 mg per day to about 480 mg per day to a male human in need of such treatment, wherein the anti-androgen is:
4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2 fluoro-N-methylbenzamide,
4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide, or
4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide;
wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist.
15. The method of claim 14 , wherein the anti-androgen is 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide.
16. The method of claim 15 , wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin.
17. The method of claim 15 , wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide (ARN-509) is administered orally to the male human at a dose of:
(a) about 30 mg per day;
(b) about 60 mg per day;
(c) about 90 mg per day;
(d) about 120 mg per day; or
(e) about 240 mg per day.
18. The method of claim 9 , 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.
19. The method of claim 3 , wherein 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide is administered orally to the male human at a dose of about 240 mg per day.
20. The method of claim 3 , wherein the GnRH agonist is leuprolide.
21. The method of claim 3 , wherein the GnRH agonist is buserelin.
22. The method of claim 3 , wherein the GnRH agonist is naferelin.
23. The method of claim 3 , wherein the GnRH agonist is histrelin.
24. The method of claim 3 , wherein the GnRH agonist is goserelin.
25. The method of claim 3 , wherein the GnRH agonist is deslorelin.