Methods and Compositions for Treating Cancer

• US 20110144016A1
• Filed: 02/24/2011
• Published: 06/16/2011
• Est. Priority Date: 08/25/2006
• Status: Active Grant

• Current Assignee: British Technology Group Ltd.
• Original Assignee: Alan H. Auerbach, Arie S. Belldegrum
• Inventors: Belldegrum, Arie S., Auerbach, Alan H.
• Granted Patent: US 8,822,438 B2
• Time in Patent Office: Days
• US Class Current: 514/9.7
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

Methods and compositions for treating cancer are described herein. More particularly, the methods for treating cancer comprise administering a 17α-hydroxylase/C_17,20-lyase inhibitor, such as abiraterone acetate (i.e., 3β-acetoxy-17-(3-pyridyl) androsta-5,16-diene), in combination with at least one additional therapeutic agent such as an anti-cancer agent or a steroid. Furthermore, disclosed are compositions comprising a 17α-hydroxylase/C_17,20-lyase inhibitor, and at least one additional therapeutic agent, such as an anti-cancer agent or a steroid.

Claims

1. A method for the treatment of a cancer in a mammal comprising administering a therapeutically effective amount of at least one 17α

-hydroxylase/C_17,20-lyase inhibitor and a therapeutically effective amount of at least one additional therapeutic agent to a patient having a cancer;

wherein the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises a compound of the formula (I) or an analog, a derivative, a metabolite or a pharmaceutically acceptable salt thereof,

2. The method of claim 1, wherein the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises abiraterone acetate or an analog, a derivative, a metabolite or a pharmaceutically acceptable salt thereof.

3. The method of claim 2, wherein the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises the mesylate salt of abiraterone acetate.

4. The method of claim 1, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 50 mg/day to about 2000 mg/day.

5. The method of claim 1, wherein the additional therapeutic agent comprises an anti-neoplastic agent, an alkylating agent, an anti-metabolite agent, an antibiotic agent, a hormonal ablation agent, an androgen ablation agent, an anti-androgen agent, or a steroid.

6. The method of claim 1, wherein the additional therapeutic agent comprises mitoxantrone, paclitaxel, docetaxel, leuprolide, goserelin, triptorelin, seocalcitol, bicalutamide, flutamide, hydrocortisone, prednisone or dexamethasone.

7. The method of claim 1, wherein the 17α

-hydroxylase/C_17,20 lyase inhibitor and the additional therapeutic agent are administered to the mammal in a single composition comprising the 17α

-hydroxylase/C_17,20 lyase inhibitor and the additional therapeutic agent.

8. The method of claim 1, wherein the 17α

-hydroxylase/C_17,20 lyase inhibitor and the additional therapeutic agent are administered separately to the mammal.

9. The method of claim 1, wherein the cancer is prostate cancer or breast cancer.

10. The method of claim 1, wherein the therapeutically effective amount of the at least one 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 0.01 mg/kg/day to about 100 mg/kg/day of abiraterone acetate and the therapeutically effective amount of the at least one additional therapeutic agent comprises about 0.1 mg/m² to about 20 mg/m² of mitoxantrone.

11. The method of claim 1 wherein the therapeutically effective amount of the at least one 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 0.01 mg/kg/day to about 100 mg/kg/day of abiraterone acetate and the therapeutically effective amount of the at least one additional therapeutic agent comprises about 1 mg/m² to about 175 mg/m² of paclitaxel.

12. The method of claim 1 wherein the therapeutically effective amount of the at least one 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 0.01 mg/kg/day to about 100 mg/kg/day of abiraterone acetate and the therapeutically effective amount of the at least one additional therapeutic agent comprises about 1 mg/m² to about 100 mg/m² of docetaxel.

13. The method of claim 1 wherein the therapeutically effective amount of the at least one 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 0.01 mg/kg/day to about 100 mg/kg/day of abiraterone acetate and the therapeutically effective amount of the at least one additional therapeutic agent comprises about 0.01 to about 200 mg of leuprolide over a period of about 3 days to about 12 months.

14. The method of claim 1 wherein the therapeutically effective amount of the at least one 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 0.01 mg/kg/day to about 100 mg/kg/day of abiraterone acetate and the therapeutically effective amount of the at least one additional therapeutic agent comprises about 20 mg of goserelin over a period of about 28 days to about 3 months.

15. The method of claim 1 wherein the therapeutically effective amount of the at least one 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 0.01 mg/kg/day to about 100 mg/kg/day of abiraterone acetate and the therapeutically effective amount of the at least one additional therapeutic agent comprises about 0.01 mg to about 20 mg of triptorelin over a period of about 1 month.

16. The method of claim 1 wherein the therapeutically effective amount of the at least one 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 0.01 mg/kg/day to about 100 mg/kg/day of abiraterone acetate and the therapeutically effective amount of the at least one additional therapeutic agent comprises about 0.1 μ

g/day to about 500 μ

g/day of seocalcitol.

17. The method of claim 1 wherein the therapeutically effective amount of the at least one 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 0.01 mg/kg/day to about 100 mg/kg/day of abiraterone acetate and the therapeutically effective amount of the at least one additional therapeutic agent comprises about 1 mg/day to about 300 mg/day of bicalcutamide.

18. The method of claim 1 wherein the therapeutically effective amount of the at least one 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 0.01 mg/kg/day to about 100 mg/kg/day of abiraterone acetate and the therapeutically effective amount of the at least one additional therapeutic agent comprises about 1 mg/day to about 2000 mg/day flutamide.

19. The method of claim 1 wherein the therapeutically effective amount of the at least one 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 50 mg/day to about 2000 mg/day of abiraterone acetate and the therapeutically effective amount of the at least one additional therapeutic agent comprises about 10 mg/day to about 250 mg/day of hydrocortisone.

20. The method of claim 1 wherein the therapeutically effective amount of the at least one 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 50 mg/day to about 2000 mg/day of abiraterone acetate and the therapeutically effective amount of the at least one additional therapeutic agent comprises about 10 mg/day to about 250 mg/day prednisone.

21. The method of claim 1 wherein the therapeutically effective amount of the at least one 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 50 mg/day to about 2000 mg/day of abiraterone acetate and the therapeutically effective amount of the at least one additional therapeutic agent comprises about 0.5 mg/day to about 25 mg/day dexamethasone.

22. A method for treating a patient having a refractory prostate or breast cancer who is currently receiving at least one treatment for cancer, the method comprising administering a therapeutically effective amount of at least one 17α

-hydroxylase/C_17,20-lyase inhibitor in addition to the at least one treatment the patient is currently receiving, wherein the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises a compound of the formula (I) or an analog, a derivative, a metabolite or pharmaceutically acceptable salt thereof,

23. The method of claim 22, wherein the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises abiraterone acetate or an analog, a derivative, a metabolite or a pharmaceutically acceptable salt thereof.

24. The method of claim 23, wherein the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises the mesylate salt of abiraterone acetate.

25. The method of claim 22, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 50 mg/day to about 2000 mg/day.

26. The method of claim 22, wherein the treatment for cancer comprises the administration of an anti-cancer agent, chemotherapy, radiation or surgery.

27. A pharmaceutical composition for the treatment of a cancer in a mammal comprising a therapeutically effective amount of at least one 17α

-hydroxylase/C_17,20-lyase inhibitor; and

at least one additional therapeutic agent;

wherein the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises a compound of the formula (I) or an analog, a derivative, a metabolite or a pharmaceutically acceptable salt thereof,

28. The composition of claim 27, wherein the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises abiraterone acetate or an analog, a derivative, a metabolite or a pharmaceutically acceptable salt thereof.

29. The composition of claim 28, wherein the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises the mesylate salt of abiraterone acetate.

30. The composition of claim 27, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 50 mg to about 500 mg.

31. The composition of claim 27, wherein the additional therapeutic agent comprises mitoxantrone, paclitaxel, docetaxel, leuprolide, goserelin, triptorelin, seocalcitol, bicalutamide, flutamide, hydrocortisone, prednisone or dexamethasone.

32. A pharmaceutical composition for the treatment of a cancer in a mammal comprising a therapeutically effective amount of abiraterone acetate;

and a therapeutically effective amount of a steroid, wherein the composition is suitable for oral administration.

33. The composition of claim 32 wherein the composition is a solid dosage form.

34. The composition of claim 32, wherein the composition comprises about 50 mg to about 500 mg of abiraterone acetate, and about 0.25 mg to about 3.5 mg of the steroid.

35. The composition of claim 32, wherein the steroid comprises hydrocortisone, prednisone, or dexamethasone.

36. The composition of claim 32, wherein the composition is in the form of a pill, tablet or capsule.