USRE49353EActiveUtility
Anti-androgens for the treatment of non-metastatic castrate-resistant prostate cancer

Assignee: ARAGON PHARMACEUTICALS INCPriority: Sep 26, 2012Filed: Aug 20, 2020Granted: Jan 3, 2023
Est. expirySep 26, 2032(~6.2 yrs left)· nominal 20-yr term from priority
A61K 31/00A61P 35/00A61K 31/4166A61K 38/09A61P 5/28A61K 31/4439A61P 5/02A61P 43/00A61P 13/08A61P 37/00A61K 2300/00H05K 999/99
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Cited by
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References
Claims
Abstract

Described herein are methods of treating non-metastatic castrate-resistant prostate cancer with anti-androgens.
Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       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  1, 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  1, 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  1, 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  1, 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  1, 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  14, wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin. 
     
     
       17. The method of claim  15  14, 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  1, 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  1, wherein the GnRH agonist is leuprolide. 
     
     
       21. The method of claim  3  1, wherein the GnRH agonist is buserelin. 
     
     
       22. The method of claim  3  1, wherein the GnRH agonist is naferelin. 
     
     
       23. The method of claim  3  1, wherein the GnRH agonist is histrelin. 
     
     
       24. The method of claim  3  1, wherein the GnRH agonist is goserelin. 
     
     
       25. The method of claim  3  1, wherein the GnRH agonist is deslorelin. 
     
     
       26. 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-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide,   wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist.   
     
     
       27. The method of claim 26, wherein the non-metastatic castration-resistant prostate cancer is a high risk non-metastatic castration-resistant prostate cancer. 
     
     
       28. The method of claim 26, wherein 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. 
     
     
       29. The method of claim 26, wherein 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 dosage schedule. 
     
     
       30. The method of claim 26, wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin. 
     
     
       31. The method of claim 26, wherein the anti-androgen is administered orally to the male human. 
     
     
       32. The method of claim 26, wherein the GnRH agonist is leuprolide. 
     
     
       33. The method of claim 26, wherein the GnRH agonist is buserelin. 
     
     
       34. The method of claim 26, wherein the GnRH agonist is naferelin. 
     
     
       35. The method of claim 26, wherein the GnRH agonist is histrelin. 
     
     
       36. The method of claim 26, wherein the GnRH agonist is goserelin. 
     
     
       37. The method of claim 26, wherein the GnRH agonist is deslorelin. 
     
     
       38. The method of claim 26, 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. 
     
     
       39. 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-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-fluoro-N-methylbenzamide,   wherein said method further comprises administering a gonadotropin releasing hormone (GnRH) agonist.   
     
     
       40. The method of claim 39, wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin. 
     
     
       41. The method of claim 39, 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. 
     
     
       42. 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-[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.   
     
     
       43. The method of claim 42, wherein the non-metastatic castration-resistant prostate cancer is a high risk non-metastatic castration-resistant prostate cancer. 
     
     
       44. The method of claim 42, wherein 4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide is administered daily to the male human. 
     
     
       45. The method of claim 42, wherein 4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-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. 
     
     
       46. The method of claim 42, wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin. 
     
     
       47. The method of claim 42, wherein the anti-androgen is administered orally to the male human. 
     
     
       48. The method of claim 42, wherein the GnRH agonist is leuprolide. 
     
     
       49. The method of claim 42, wherein the GnRH agonist is buserelin. 
     
     
       50. The method of claim 42, wherein the GnRH agonist is naferelin. 
     
     
       51. The method of claim 42, wherein the GnRH agonist is histrelin. 
     
     
       52. The method of claim 42, wherein the GnRH agonist is goserelin. 
     
     
       53. The method of claim 42, wherein the GnRH agonist is deslorelin. 
     
     
       54. 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-[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.   
     
     
       55. The method of claim 54, wherein the GnRH agonist is leuprolide, buserelin, naferelin, histrelin, goserelin or deslorelin.
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