METHODS FOR TREATING CANCER USING 17alpha-HYDROXYLASE/C17,20-LYASE INHIBITORS

• US 20090124587A1
• Filed: 07/11/2008
• Published: 05/14/2009
• Est. Priority Date: 07/12/2007
• Status: Abandoned Application

• Current Assignee: Alan H. Auerbach, Arie S. Belldegrun
• Original Assignee: Alan H. Auerbach, Arie S. Belldegrun
• Inventors: Auerbach, Alan H., Belldegrun, Arie S.
• Application Number:
  US12/171,352
• Publication Number:
  US 20090124587A1
• Time in Patent Office: Days
• US Class Current: 514/176
• 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 for treating certain cancers in patients, such as mammals, using certain 17α-hydroxylase/C_17,20-lyase inhibitors are discussed herein. More particularly, methods for treating cancers comprising administering a 17α-hydroxylase/C_17,20-lyase inhibitor, such as abiraterone acetate (i.e. 3β-acetoxy-17-(3-pyridyl) androsta-5,16-diene) and metabolites thereof are described. In addition, methods for treating cancers that are refractory to hormone therapy or that are refractory to chemotherapy are also discussed. Finally novel dosing regimens and novel uses of the compounds discussed herein are disclosed.

Claims

1. A method for the treatment of a patient having cancer comprising administering to the patient having cancer that is (A) refractory to a chemotherapy, or (B) refractory to a chemotherapy and a hormone therapy, a therapeutically effective amount of a 17α

-hydroxylase/C_17,20-lyase inhibitor.

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

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

wherein X represents the residue of the A, B and C rings of a steroid which can be, without limitation, androstan-3α

- or 3β

-ol; and

rost-5-en-3α

- or 3β

-ol; and

rost-4-en-3-one; and

rost-2-ene; and

rost-4-ene; and

rost-5-ene; and

rosta-5,7-dien-3α

or 3β

-ol; and

rosta-1,4-dien-3-one; and

rosta-3,5-diene; and

rosta-3,5-diene-3-ol;

estra-1,3,5[10]-triene;

estra-1,3,5[10]-trien-3-ol;

5α

-androstan-3-one; and

rost-4-ene-3,11-dione;

6-fluoroandrost-4-ene-3-one;

or androstan-4-ene-3,6-dione;

each of which, where structurally permissible, can be further derivatized in one or more of the following ways, including, but not limited to, to form 3-esters;

to have one or more carbon or carbon ring double bonds in any of the 5,6-, 6,7-, 7,8-, 9,11- and 11,12-positions;

as 3-oximes;

as 3-methylenes;

as 3-carboxylates;

as 3-nitriles;

as 3-nitros;

as 3-desoxy derivatives;

to have one or more hydroxy, halo, C_1-4-alkyl, trifluoro-methyl, C_1-4-alkoxy, C_1-4-alkanoyloxy, benzoyloxy, oxo, methylene or alkenyl substituents in the A, B, or C-ring;

or to be 19-nor;

R represents a hydrogen atom or an alkyl group of 1-4 carbon atoms;

R¹⁴ represents a hydrogen atom, a halogen atom or an alkyl group of 1 to 4 carbon atoms;

each of the R¹⁵ substituents independently represents a hydrogen atom or an alkyl or alkoxy group of 1-4 carbon atoms, a hydroxy group or an alkylcarbonyloxy group of 2 to 5 carbon atoms or together represent an oxo or methylene group or R¹⁴ and one of the R¹⁵ groups together represent a double bond and the other R¹⁵ group represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms; and

R¹⁶ represents a hydrogen atom, halogen atom, or an alkyl group of 1 to 4 carbon atoms,

in the form of the free bases or pharmaceutically acceptable acid addition salts, but excluding 3β

-acetoxy-17-(3-pyridyl)androsta-5,14,16-triene, 3β

,15α

- and 3β

,15β

-diacetoxy-17-(3-pyridyl)androsta-5,16-diene and 3β

-methoxy-17-(3-pyridyl-5α

-androst-16-ene.

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

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

4. The method of claim 3, wherein the abiraterone acetate is prepared from a mesylate salt of abiraterone acetate.

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

-hydroxylase/C_17,20-lyase inhibitor is about 100 mg/day to about 2500 mg/day;

about 250 mg/day to about 2000 mg/day;

or about 1000 mg/day or more.

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

-hydroxylase/C_17,20-lyase inhibitor is administered at a frequency comprising (A) once per day;

(B) once per day continuously during a first treatment cycle of about 28 days;

(C) once per day continuously during a first treatment cycle of about 28 days, wherein the first treatment cycle is followed by a first non-treatment period during which the 17α

-hydroxylase/C_17,20-lyase inhibitor is not administered to the patient;

or (D) once per day continuously during a first treatment cycle of about 28 days, wherein the first treatment cycle is followed by a first non-treatment period during which the 17α

-hydroxylase/C_17,20-lyase inhibitor is not administered to the patient, and wherein the first non-treatment period is followed by a second treatment cycle of about 28 days.

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

-hydroxylase/C_17,20-lyase inhibitor is administered orally.

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

-hydroxylase/C_17,20-lyase inhibitor is contained in a pharmaceutical composition that further comprises a pharmaceutically acceptable carrier or vehicle.

9. The method of claim 8, wherein the pharmaceutical composition is in the form of a tablet or a capsule.

10. The method of claim 1, further comprising administering the 17α

-hydroxylase/C_17,20-lyase inhibitor (A) with food, (B) about 1 minute after consumption of food by the patient, (C) about 1 hour after consumption of food by the patient, or (D) once per day with food continuously during a first treatment course of about 28 days.

11. The method of claim 1, wherein the cancer is of the prostate, breast, ovary, testicle or other reproductive organ, bone, or lymph node.

12. The method of claim 1, wherein the cancer comprises an androgen-responsive cancer, a testosterone-responsive cancer, or an estrogen-responsive cancer.

13. The method of claim 1, wherein the cancer has metastasized or the cancer is a metastasis.

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

-hydroxylase/C_17,20-lyase inhibitor is administered while the patient is receiving another treatment comprising a chemotherapy or a hormone therapy.

15. The method of claim 1, wherein the patient is (A) about 30 to about 85 years old;

or (B) about 65 years old or older.

16. The method of claim 1, wherein the patient that is refractory to a chemotherapy is hormone therapy-naï

ve.

17. The method of claim 1, wherein the patient has a baseline plasma concentration of PSA of about 0.5 ng/mL or more prior to administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

18. The method of claim 17, wherein the patient has a baseline plasma concentration of PSA of about 4.0 ng/mL or more prior to administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

19. The method of claim 1, wherein the patient has been castrated prior to administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

20. The method of claim 1, wherein the patient has a first plasma concentration of PSA before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor and the patient has a second plasma concentration of PSA after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second plasma concentration of PSA is less than the first plasma concentration of PSA.

21. The method of claim 20, wherein the second plasma concentration of PSA is less than the first plasma concentration of PSA for a time period of at least 10 days.

22. The method of claim 20, wherein the second plasma concentration of PSA is about 50 ng/mL or less.

23. The method of claim 20, wherein the second plasma concentration of PSA is about 50% or less of the first plasma concentration of PSA.

24. The method of claim 20, wherein the second plasma concentration of PSA is at or below castration levels of PSA.

25. The method of claim 24, wherein the second plasma concentration of PSA is at or below castration levels of PSA for a time period of at least 10 days.

26. The method of claim 1, wherein the patient has a first plasma concentration of testosterone before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor and the patient has a second plasma concentration of testosterone after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second plasma concentration of testosterone is less than the first plasma concentration of testosterone.

27. The method of claim 26, wherein the second plasma concentration of testosterone is about 50% or less of the first plasma concentration of testosterone.

28. The method of claim 26, wherein the second plasma concentration of testosterone is at or below castration levels of testosterone.

29. The method of claim 28, wherein the second plasma concentration of testosterone is below castration levels of testosterone for a time period of at least 10 days.

30. The method of claim 1, wherein the patient has a first number of circulating tumor cells before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor and the patient has a second number of circulating tumor cells after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second number of circulating tumor cells is fewer than the first number of circulating tumor cells.

31. The method of claim 30, wherein the second number of circulating tumor cells is about 75% or less of the first number of circulating tumor cells.

32. The method claim 1, wherein the cancer results in a tumor of a first tumor mass before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and wherein after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor the first tumor mass of the tumor is reduced to a second tumor mass that is smaller than the first tumor mass.

33. The method of claim 32, wherein the second tumor mass is about 50% or less of the first tumor mass.

34. The method of claim 1, wherein the cancer has metastasized to a bone or a lymph node before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and wherein the size of the metastasis in the patient is reduced or stabilized after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

35. The method of claim 34, wherein the size of the metastasis is reduced by 30% or more.

36. The method of claim 1, wherein the patient has a first plasma concentration of ALP before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and the patient has a second plasma concentration of ALP after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second plasma concentration of ALP is less than the first plasma concentration of ALP.

37. The method of claim 36, wherein the second plasma concentration of ALP is about 30% or less of the first plasma concentration of ALP.

38. The method claim 1, wherein the patient experiences a first level of pain before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and the patient experiences a second level of pain after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the first level of pain is greater than the second level of pain.

39. The method of claim 1, wherein the patient was administered a first amount of a pain-relieving agent before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and the patient is administered a second amount of the pain-relieving agent after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the first amount of the pain-relieving agent is greater than the second amount of the pain-relieving agent.

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

-hydroxylase/C_17,20-lyase inhibitor provides a maximum plasma concentration of the 17α

-hydroxylase/C_17,20-lyase inhibitor or a metabolite thereof, in the patient at about 1 hour to about 8 hours after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

41. The method of claim 40, wherein the maximum plasma concentration occurs at about 4 hours to about 6 hours after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

42. The method of claim 40, wherein the metabolite is abiraterone.

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

-hydroxylase/C_17,20-lyase inhibitor provides a maximum plasma concentration of the 17α

-hydroxylase/C_17,20-lyase inhibitor, or a metabolite thereof, in the patient of about 50 nmol/L to about 5000 nmol/L.

44. The method of claim 43, wherein the maximum plasma concentration is about 250 nmol/L to about 4000 nmol/L.

45. The method of claim 43, wherein the maximum plasma concentration is about 200 nmol/L to about 2500 nmol/L.

46. The method of claim 43, wherein the metabolite is abiraterone.

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

-hydroxylase/C_17,20-lyase inhibitor provides an area under the curve of a plot of plasma concentration of the 17α

-hydroxylase/C_17,20-lyase inhibitor, or a metabolite thereof, versus time of about 50 hr*nmol/L to about 25,000 hr*nmol/L.

48. The method of claim 47, wherein the area under the curve is about 1,000 hr*nmol/L to about 20,000 hr*nmol/L.

49. The method of claim 48, wherein the area under the curve is about 5,000 hr*nmol/L to about 18,000 hr*nmol/L.

50. A method for the treatment of a patient having cancer comprising administering to the patient having cancer that is (A) refractory to a hormone therapy, or (B) refractory to a hormone therapy and a chemotherapy, a therapeutically effective amount of a 17α

-hydroxylase/C_17,20-lyase inhibitor with food.

51. The method of claim 50, wherein the 17α

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

wherein X represents the residue of the A, B and C rings of a steroid which can be, without limitation, androstan-3α

- or 3β

-ol; and

rost-5-en-3α

- or 3β

-ol; and

rost-4-en-3-one; and

rost-2-ene; and

rost-4-ene; and

rost-5-ene; and

rosta-5,7-dien-3α

or 3β

-ol; and

rosta-1,4-dien-3-one; and

rosta-3,5-diene; and

rosta-3,5-diene-3-ol;

estra-1,3,5[10]-triene;

estra-1,3,5[10]-trien-3-ol;

5α

-androstan-3-one; and

rost-4-ene-3,11-dione;

6-fluoroandrost-4-ene-3-one;

or androstan-4-ene-3,6-dione;

each of which, where structurally permissible, can be further derivatized in one or more of the following ways, including, but not limited to, to form 3-esters;

to have one or more carbon or carbon ring double bonds in any of the 5,6-, 6,7-, 7,8-, 9,11- and 11,12-positions;

as 3-oximes;

as 3-methylenes;

as 3-carboxylates;

as 3-nitriles;

as 3-nitros;

as 3-desoxy derivatives;

to have one or more hydroxy, halo, C_1-4-alkyl, trifluoro-methyl, C_1-4-alkoxy, C_1-4-alkanoyloxy, benzoyloxy, oxo, methylene or alkenyl substituents in the A, B, or C-ring;

or to be 19-nor;

R represents a hydrogen atom or an alkyl group of 1-4 carbon atoms;

R¹⁴ represents a hydrogen atom, a halogen atom or an alkyl group of 1 to 4 carbon atoms;

each of the R¹⁵ substituents independently represents a hydrogen atom or an alkyl or alkoxy group of 1-4 carbon atoms, a hydroxy group or an alkylcarbonyloxy group of 2 to 5 carbon atoms or together represent an oxo or methylene group or R¹⁴ and one of the R¹⁵ groups together represent a double bond and the other R¹⁵ group represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms; and

R¹⁶ represents a hydrogen atom, halogen atom, or an alkyl group of 1 to 4 carbon atoms, in the form of the free bases or pharmaceutically acceptable acid addition salts, but excluding 3β

-acetoxy-17-(3-pyridyl)androsta-5,14,16-triene, 3β

,15α

- and 3β

,15β

-diacetoxy-17-(3-pyridyl)androsta-5,16-diene and 3β

-methoxy-17-(3-pyridyl-5α

-androst-16-ene.

52. The method of claim 50, wherein the 17α

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

53. The method of claim 52, wherein the abiraterone acetate is prepared from a mesylate salt of abiraterone acetate.

54. The method of claim 50, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is about 100 mg/day to about 2500 mg/day;

about 250 mg/day to about 2000 mg/day;

or about 1000 mg/day or more.

55. The method of claim 50, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is administered at a frequency comprising (A) once per day;

(B) once per day continuously during a first treatment cycle of about 28 days;

(C) once per day continuously during a first treatment cycle of about 28 days, wherein the first treatment cycle is followed by a first non-treatment period during which the 17α

-hydroxylase/C_17,20-lyase inhibitor is not administered to the patient;

or (D) once per day continuously during a first treatment cycle of about 28 days, wherein the first treatment cycle is followed by a first non-treatment period during which the 17α

-hydroxylase/C_17,20-lyase inhibitor is not administered to the patient, and wherein the first non-treatment period is followed by a second treatment cycle of about 28 days.

56. The method of claim 50, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is administered orally.

57. The method of claim 50, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is contained in a pharmaceutical composition that further comprises a pharmaceutically acceptable carrier or vehicle.

58. The method of claim 57, wherein the pharmaceutical composition is in the form of a tablet or a capsule.

59. The method of claim 50, further comprising administering the 17α

-hydroxylase/C_17,20-lyase inhibitor once per day with food continuously during a first treatment course of about 28 days.

60. The method of claim 50, wherein the cancer is of the prostate, breast, ovary, testicle or other reproductive organ, bone, or lymph node.

61. The method of claim 50, wherein the cancer comprises an androgen-responsive cancer, a testosterone-responsive cancer, or an estrogen-responsive cancer.

62. The method of claim 50, wherein the cancer has metastasized or the cancer is a metastasis.

63. The method of claim 50, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is administered while the patient is receiving another treatment comprising a chemotherapy or a hormone therapy.

64. The method of claim 50, wherein the patient is (A) about 30 to about 85 years old;

or (B) about 65 years old or older.

65. The method of claim 50, wherein the patient that is refractory to a hormone therapy is chemotherapy-naï

ve.

66. The method of claim 50, wherein the patient has a baseline plasma concentration of PSA of about 0.5 ng/mL or more prior to administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

67. The method of claim 66, wherein the patient has a baseline plasma concentration of PSA of about 4.0 ng/mL or more prior to administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

68. The method of claim 50, wherein the patient has been castrated prior to administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

69. The method of claim 50, wherein the patient has a first plasma concentration of PSA before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor and the patient has a second plasma concentration of PSA after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second plasma concentration of PSA is less than the first plasma concentration of PSA.

70. The method of claim 69, wherein the second plasma concentration of PSA is less than the first plasma concentration of PSA for a time period of at least 10 days.

71. The method of claim 69, wherein the second plasma concentration of PSA is about 50 ng/mL or less.

72. The method of claim 69, wherein the second plasma concentration of PSA is about 50% or less of the first plasma concentration of PSA.

73. The method of claim 69, wherein the second plasma concentration of PSA is at or below castration levels of PSA.

74. The method of claim 73, wherein the second plasma concentration of PSA is at or below castration levels of PSA for a time period of at least 10 days.

75. The method of claim 50, wherein the patient has a first plasma concentration of testosterone before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor and the patient has a second plasma concentration of testosterone after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second plasma concentration of testosterone is less than the first plasma concentration of testosterone.

76. The method of claim 75, wherein the second plasma concentration of testosterone is about 50% or less of the first plasma concentration of testosterone.

77. The method of claim 75, wherein the second plasma concentration of testosterone is at or below castration levels of testosterone.

78. The method of claim 77, wherein the second plasma concentration of testosterone is below castration levels of testosterone for a time period of at least 10 days.

79. The method of claim 50, wherein the patient has a first number of circulating tumor cells before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor and the patient has a second number of circulating tumor cells after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second number of circulating tumor cells is fewer than the first number of circulating tumor cells.

80. The method of claim 79, wherein the second number of circulating tumor cells is about 75% or less of the first number of circulating tumor cells.

81. The method claim 50, wherein the cancer results in a tumor of a first tumor mass before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and wherein after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor the first tumor mass of the tumor is reduced to a second tumor mass that is smaller than the first tumor mass.

82. The method of claim 81, wherein the second tumor mass is about 50% or less of the first tumor mass.

83. The method of claim 50, wherein the cancer has metastasized to a bone or a lymph node before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17-20-lyase inhibitor, and wherein the size of the metastasis in the patient is reduced or stabilized after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

84. The method of claim 83, wherein the size of the metastasis is reduced by 30% or more.

85. The method of claim 50, wherein the patient has a first plasma concentration of ALP before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and the patient has a second plasma concentration of ALP after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second plasma concentration of ALP is less than the first plasma concentration of ALP.

86. The method of claim 85, wherein the second plasma concentration of ALP is about 30% or less of the first plasma concentration of ALP.

87. The method claim 50, wherein the patient experiences a first level of pain before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and the patient experiences a second level of pain after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the first level of pain is greater than the second level of pain.

88. The method of claim 50, wherein the patient was administered a first amount of a pain-relieving agent before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and the patient is administered a second amount of the pain-relieving agent after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the first amount of the pain-relieving agent is greater than the second amount of the pain-relieving agent.

89. The method of claim 50, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor provides a maximum plasma concentration of the 17α

-hydroxylase/C_17,20-lyase inhibitor, or a metabolite thereof, in the patient at about 1 hour to about 8 hours after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

90. The method of claim 89, wherein the maximum plasma concentration occurs at about 4 hours to about 6 hours after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

91. The method of claim 89, wherein the metabolite is abiraterone.

92. The method of claim 50, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor provides a maximum plasma concentration of the 17α

-hydroxylase/C_17,20-lyase inhibitor, or a metabolite thereof, in the patient of about 50 nmol/L to about 5000 nmol/L.

93. The method of claim 92, wherein the maximum plasma concentration is about 250 nmol/L to about 4000 nmol/L.

94. The method of claim 92, wherein the maximum plasma concentration is about 200 nmol/L to about 2500 nmol/L.

95. The method of claim 92, wherein the metabolite is abiraterone.

96. The method of claim 50, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor provides an area under the curve of a plot of plasma concentration of the 17α

-hydroxylase/C_17,20-lyase inhibitor, or a metabolite thereof, versus time of about 50 hr*nmol/L to about 25,000 hr*nmol/L.

97. The method of claim 96, wherein the area under the curve is about 1,000 hr*nmol/L to about 20,000 hr*nmol/L.

98. The method of claim 97, wherein the area under the curve is about 5,000 hr*nmol/L to about 18,000 hr*nmol/L.

99. A method for the treatment of a patient having cancer comprising administering to the patient having cancer a therapeutically effective amount of a 17α

-hydroxylase/C_17,20-lyase inhibitor comprising about 825 mg/day or more.

100. The method of claim 99, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor comprises about 1000 mg/day or more.

101. The method of claim 99, wherein the 17α

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

wherein X represents the residue of the A, B and C rings of a steroid which can be, without limitation, androstan-3α

- or 3β

-ol; and

rost-5-en-3α

- or 3β

-ol; and

rost-4-en-3-one; and

rost-2-ene; and

rost-4-ene; and

rost-5-ene; and

rosta-5,7-dien-3α

or 3β

-ol; and

rosta-1,4-dien-3-one; and

rosta-3,5-diene; and

rosta-3,5-diene-3-ol;

estra-1,3,5[10]-triene;

estra-1,3,5[10]-trien-3-ol;

5α

-androstan-3-one; and

rost-4-ene-3,11-dione;

6-fluoroandrost-4-ene-3-one;

or androstan-4-ene-3,6-dione;

each of which, where structurally permissible, can be further derivatized in one or more of the following ways, including, but not limited to, to form 3-esters;

to have one or more carbon or carbon ring double bonds in any of the 5,6-, 6,7-, 7,8-, 9,11- and 11,12-positions;

as 3-oximes;

as 3-methylenes;

as 3-carboxylates;

as 3-nitriles;

as 3-nitros;

as 3-desoxy derivatives;

to have one or more hydroxy, halo, C_1-4-alkyl, trifluoro-methyl, C_1-4-alkoxy, C_1-4-alkanoyloxy, benzoyloxy, oxo, methylene or alkenyl substituents in the A, B, or C-ring;

or to be 19-nor;

R represents a hydrogen atom or an alkyl group of 1-4 carbon atoms;

R¹⁴ represents a hydrogen atom, a halogen atom or an alkyl group of 1 to 4 carbon atoms;

each of the R¹⁵ substituents independently represents a hydrogen atom or an alkyl or alkoxy group of 1-4 carbon atoms, a hydroxy group or an alkylcarbonyloxy group of 2 to 5 carbon atoms or together represent an oxo or methylene group or R¹⁴ and one of the R¹⁵ groups together represent a double bond and the other R¹⁵ group represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms; and

R¹⁶ represents a hydrogen atom, halogen atom, or an alkyl group of 1 to 4 carbon atoms,

in the form of the free bases or pharmaceutically acceptable acid addition salts, but excluding 3β

-acetoxy-17-(3-pyridyl)androsta-5,14,16-triene, 3β

,15α

- and 3β

,15β

-diacetoxy-17-(3-pyridyl)androsta-5,16-diene and 3β

-methoxy-17-(3-pyridyl-5α

-androst-16-ene.

102. The method of claim 99, wherein the 17α

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

103. The method of claim 102, wherein the abiraterone acetate is prepared from a mesylate salt of abiraterone acetate.

104. The method of claim 99, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is administered at a frequency comprising (A) once per day;

(B) once per day continuously during a first treatment cycle of about 28 days;

(C) once per day continuously during a first treatment cycle of about 28 days, wherein the first treatment cycle is followed by a first non-treatment period during which the 17α

-hydroxylase/C_17,20-lyase inhibitor is not administered to the patient;

or (D) once per day continuously during a first treatment cycle of about 28 days, wherein the first treatment cycle is followed by a first non-treatment period during which the 17α

-hydroxylase/C_17,20-lyase inhibitor is not administered to the patient, and wherein the first non-treatment period is followed by a second treatment cycle of about 28 days.

105. The method of claim 99, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is administered orally.

106. The method of claim 99, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is contained in a pharmaceutical composition that further comprises a pharmaceutically acceptable carrier or vehicle.

107. The method of claim 106, wherein the pharmaceutical composition is in the form of a tablet or a capsule.

108. The method of claim 99, further comprising administering the 17α

-hydroxylase/C_17,20-lyase inhibitor (A) with food, (B) about 1 minute after consumption of food by the patient, (C) about 1 hour after consumption of food by the patient, or (D) once per day with food continuously during a first treatment course of about 28 days.

109. The method of claim 99, wherein the cancer is of the prostate, breast, ovary, testicle or other reproductive organ, bone, or lymph node.

110. The method of claim 99, wherein the cancer comprises an androgen-responsive cancer, a testosterone-responsive cancer, or an estrogen-responsive cancer.

111. The method of claim 99, wherein the cancer has metastasized or the cancer is a metastasis.

112. The method of claim 99, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is administered while the patient is receiving another treatment comprising a chemotherapy or a hormone therapy.

113. The method of claim 99, wherein the patient is (A) about 30 to about 85 years old;

or (B) about 65 years old or older.

114. The method of claim 99, wherein the patient is chemotherapy-naï

ve.

115. The method of claim 99, wherein the patient is hormone therapy-naï

ve.

116. The method of claim 99, wherein the patient has a baseline plasma concentration of PSA of about 0.5 ng/mL or more prior to administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

117. The method of claim 116, wherein the patient has a baseline plasma concentration of PSA of about 4.0 ng mL or more prior to administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

118. The method of claim 99, wherein the patient has been castrated prior to administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

119. The method of claim 99, wherein the patient has a first plasma concentration of PSA before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor and the patient has a second plasma concentration of PSA after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second plasma concentration of PSA is less than the first plasma concentration of PSA.

120. The method of claim 119, wherein the second plasma concentration of PSA is less than the first plasma concentration of PSA for a time period of at least 10 days.

121. The method of claim 119, wherein the second plasma concentration of PSA is about 50 ng/mL or less.

122. The method of claim 119, wherein the second plasma concentration of PSA is about 50% or less of the first plasma concentration of PSA.

123. The method of claim 119, wherein the second plasma concentration of PSA is at or below castration levels of PSA.

124. The method of claim 123, wherein the second plasma concentration of PSA is at or below castration levels of PSA for a time period of at least 10 days.

125. The method of claim 99, wherein the patient has a first plasma concentration of testosterone before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor and the patient has a second plasma concentration of testosterone after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second plasma concentration of testosterone is less than the first plasma concentration of testosterone.

126. The method of claim 125, wherein the second plasma concentration of testosterone is about 50% or less of the first plasma concentration of testosterone.

127. The method of claim 125, wherein the second plasma concentration of testosterone is at or below castration levels of testosterone.

128. The method of claim 127, wherein the second plasma concentration of testosterone is below castration levels of testosterone for a time period of at least 10 days.

129. The method of claim 99, wherein the patient has a first number of circulating tumor cells before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor and the patient has a second number of circulating tumor cells after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second number of circulating tumor cells is fewer than the first number of circulating tumor cells.

130. The method of claim 129, wherein the second number of circulating tumor cells is about 75% or less of the first number of circulating tumor cells.

131. The method claim 99, wherein the cancer results in a tumor of a first tumor mass before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and wherein after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor the first tumor mass of the tumor is reduced to a second tumor mass that is smaller than the first tumor mass.

132. The method of claim 131, wherein the second tumor mass is about 50% or less of the first tumor mass.

133. The method of claim 99, wherein the cancer has metastasized to a bone or a lymph node before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and wherein the size of the metastasis in the patient is reduced or stabilized after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

134. The method of claim 133, wherein the size of the metastasis is reduced by 30% or more.

135. The method of claim 99, wherein the patient has a first plasma concentration of ALP before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and the patient has a second plasma concentration of ALP after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second plasma concentration of ALP is less than the first plasma concentration of ALP.

136. The method of claim 135, wherein the second plasma concentration of ALP is about 30% or less of the first plasma concentration of ALP.

137. The method claim 99, wherein the patient experiences a first level of pain before administration of the therapeutically effective amount of the 177α

-hydroxylase/C_17,20-lyase inhibitor, and the patient experiences a second level of pain after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the first level of pain is greater than the second level of pain.

138. The method of claim 99, wherein the patient was administered a first amount of a pain-relieving agent before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and the patient is administered a second amount of the pain-relieving agent after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the first amount of the pain-relieving agent is greater than the second amount of the pain-relieving agent.

139. The method of claim 99, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor provides a maximum plasma concentration of the 17α

-hydroxylase/C_17,20-lyase inhibitor, or a metabolite thereof, in the patient at about 1 hour to about 8 hours after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

140. The method of claim 139, wherein the maximum plasma concentration occurs at about 4 hours to about 6 hours after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

141. The method of claim 139, wherein the metabolite is abiraterone.

142. The method of claim 99, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor provides a maximum plasma concentration of the 17α

-hydroxylase/C_17,20-lyase inhibitor, or a metabolite thereof, in the patient of about 50 nmol/L to about 5000 nmol/L.

143. The method of claim 142, wherein the maximum plasma concentration is about 250 nmol/L to about 4000 nmol/L.

144. The method of claim 142, wherein the maximum plasma concentration is about 200 nmol/L to about 2500 nmol/L.

145. The method of claim 142, wherein the metabolite is abiraterone.

146. The method of claim 99, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor provides an area under the curve of a plot of plasma concentration of the 17α

-hydroxylase/C_17,20-lyase inhibitor, or a metabolite thereof, versus time of about 50 hr*nmol/L to about 25,000 hr*nmol/L.

147. The method of claim 146, wherein the area under the curve is about 1,000 hr*nmol/L to about 20,000 hr*nmol/L.

148. The method of claim 147, wherein the area under the curve is about 5,000 hr*nmol/L to about 18,000 hr*nmol/L.

149. A method for the treatment of a patient having cancer comprising administering to the patient having cancer a therapeutically effective amount of a 17α

-hydroxylase/C_17,20-lyase inhibitor with food.

150. The method of claim 149, wherein the 17α

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

wherein X represents the residue of the A, B and C rings of a steroid which can be, without limitation, androstan-3α

- or 3β

-ol; and

rost-5-en-3α

- or 3β

-ol; and

rost-4-en-3-one; and

rost-2-ene; and

rost-4-ene; and

rost-5-ene; and

rosta-5,7-dien-3α

or 3β

-ol; and

rosta-1,4-dien-3-one; and

rosta-3,5-diene; and

rosta-3,5-diene-3-ol;

estra-1,3,5[10]-triene;

estra-1,3,5[10]-trien-3-ol;

5α

-androstan-3-one; and

rost-4-ene-3,11-dione;

6-fluoroandrost-4-ene-3-one;

or androstan-4-ene-3,6-dione;

each of which, where structurally permissible, can be further derivatized in one or more of the following ways, including, but not limited to, to form 3-esters;

to have one or more carbon or carbon ring double bonds in any of the 5,6-, 6,7-, 7,8-, 9,11- and 11,12-positions;

as 3-oximes;

as 3-methylenes;

as 3-carboxylates;

as 3-nitriles;

as 3-nitros;

as 3-desoxy derivatives;

to have one or more hydroxy, halo, C_1-4-alkyl, trifluoro-methyl, C_1-4-alkoxy, C_1-4-alkanoyloxy, benzoyloxy, oxo, methylene or alkenyl substituents in the A, B, or C-ring;

or to be 19-nor;

R represents a hydrogen atom or an alkyl group of 1-4 carbon atoms;

R¹⁴ represents a hydrogen atom, a halogen atom or an alkyl group of 1 to 4 carbon atoms;

each of the R¹⁵ substituents independently represents a hydrogen atom or an alkyl or alkoxy group of 1-4 carbon atoms, a hydroxy group or an alkylcarbonyloxy group of 2 to 5 carbon atoms or together represent an oxo or methylene group or R¹⁴ and one of the R¹⁵ groups together represent a double bond and the other R¹⁵ group represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms; and

R¹⁶ represents a hydrogen atom, halogen atom, or an alkyl group of 1 to 4 carbon atoms,

in the form of the free bases or pharmaceutically acceptable acid addition salts, but excluding 3β

-acetoxy-17-(3-pyridyl)androsta-5,14,16-triene, 3β

, 15α

- and 3β

,15β

-diacetoxy-17-(3-pyridyl)androsta-5,16-diene and 3β

-methoxy-17-(3-pyridyl-5α

-androst-16-ene.

151. The method of claim 149, wherein the 17α

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

152. The method of claim 151, wherein the abiraterone acetate is prepared from a mesylate salt of abiraterone acetate.

153. The method of claim 149, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is about 100 mg/day to about 2500 mg/day;

about 250 mg/day to about 2000 mg/day;

or about 1000 mg/day or more.

154. The method of claim 149, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is administered at a frequency comprising (A) once per day;

(B) once per day continuously during a first treatment cycle of about 28 days;

(C) once per day continuously during a first treatment cycle of about 28 days, wherein the first treatment cycle is followed by a first non-treatment period during which the 17α

-hydroxylase/C_17,20-lyase inhibitor is not administered to the patient;

or (D) once per day continuously during a first treatment cycle of about 28 days, wherein the first treatment cycle is followed by a first non-treatment period during which the 17α

-hydroxylase/C_17,20-lyase inhibitor is not administered to the patient, and wherein the first non-treatment period is followed by a second treatment cycle of about 28 days.

155. The method of claim 149, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is administered orally.

156. The method of claim 149, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is contained in a pharmaceutical composition that further comprises a pharmaceutically acceptable carrier or vehicle.

157. The method of claim 156, wherein the pharmaceutical composition is in the form of a tablet or a capsule.

158. The method of claim 149, further comprising administering the 17α

-hydroxylase/C_17,20-lyase inhibitor once per day with food continuously during a first treatment course of about 28 days.

159. The method of claim 149, wherein the cancer is of the prostate, breast, ovary, testicle or other reproductive organ, bone, or lymph node.

160. The method of claim 149, wherein the cancer comprises an androgen-responsive cancer, a testosterone-responsive cancer, or an estrogen-responsive cancer.

161. The method of claim 149, wherein the cancer has metastasized or the cancer is a metastasis.

162. The method of claim 149, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor is administered while the patient is receiving another treatment comprising a chemotherapy or a hormone therapy.

163. The method of claim 149, wherein the patient is (A) about 30 to about 85 years old;

or (B) about 65 years old or older.

164. The method of claim 149, wherein the patient is chemotherapy-naï

ve.

165. The method of claim 149, wherein the patient is hormone therapy-naï

ve.

166. The method of claim 149, wherein the patient has a baseline plasma concentration of PSA of about 0.5 ng/mL or more prior to administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

167. The method of claim 166, wherein the patient has a baseline plasma concentration of PSA of about 4.0 ng/mL or more prior to administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

168. The method of claim 149, wherein the patient has been castrated prior to administration of the therapeutically effective amount of the 17-hydroxylase/C_17,20-lyase inhibitor.

169. The method of claim 149, wherein the patient has a first plasma concentration of PSA before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor and the patient has a second plasma concentration of PSA after administration of the therapeutically effective amount of the 17-hydroxylase/C_17,20-lyase inhibitor, in which the second plasma concentration of PSA is less than the first plasma concentration of PSA.

170. The method of claim 169, wherein the second plasma concentration of PSA is less than the first plasma concentration of PSA for a time period of at least 10 days.

171. The method of claim 169, wherein the second plasma concentration of PSA is about 50 ng/mL or less.

172. The method of claim 169, wherein the second plasma concentration of PSA is about 50% or less of the first plasma concentration of PSA.

173. The method of claim 169, wherein the second plasma concentration of PSA is at or below castration levels of PSA.

174. The method of claim 173, wherein the second plasma concentration of PSA is at or below castration levels of PSA for a time period of at least 10 days.

175. The method of claim 149, wherein the patient has a first plasma concentration of testosterone before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor and the patient has a second plasma concentration of testosterone after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second plasma concentration of testosterone is less than the first plasma concentration of testosterone.

176. The method of claim 175, wherein the second plasma concentration of testosterone is about 50% or less of the first plasma concentration of testosterone.

177. The method of claim 175, wherein the second plasma concentration of testosterone is at or below castration levels of testosterone.

178. The method of claim 177, wherein the second plasma concentration of testosterone is below castration levels of testosterone for a time period of at least 10 days.

179. The method of claim 149, wherein the patient has a first number of circulating tumor cells before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor and the patient has a second number of circulating tumor cells after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second number of circulating tumor cells is fewer than the first number of circulating tumor cells.

180. The method of claim 179, wherein the second number of circulating tumor cells is about 75% or less of the first number of circulating tumor cells.

181. The method claim 149, wherein the cancer results in a tumor of a first tumor mass before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and wherein after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor the first tumor mass of the tumor is reduced to a second tumor mass that is smaller than the first tumor mass.

182. The method of claim 181, wherein the second tumor mass is about 50% or less of the first tumor mass.

183. The method of claim 149, wherein the cancer has metastasized to a bone or a lymph node before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and wherein the size of the metastasis in the patient is reduced or stabilized after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

184. The method of claim 183, wherein the size of the metastasis is reduced by 30% or more.

185. The method of claim 149, wherein the patient has a first plasma concentration of ALP before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and the patient has a second plasma concentration of ALP after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the second plasma concentration of ALP is less than the first plasma concentration of ALP.

186. The method of claim 185, wherein the second plasma concentration of ALP is about 30% or less of the first plasma concentration of ALP.

187. The method claim 149, wherein the patient experiences a first level of pain before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and the patient experiences a second level of pain after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the first level of pain is greater than the second level of pain.

188. The method of claim 149, wherein the patient was administered a first amount of a pain-relieving agent before administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, and the patient is administered a second amount of the pain-relieving agent after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor, in which the first amount of the pain-relieving agent is greater than the second amount of the pain-relieving agent.

189. The method of claim 149, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor provides a maximum plasma concentration of the 17α

-hydroxylase/C_17,20-lyase inhibitor, or a metabolite thereof, in the patient at about 1 hour to about 8 hours after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

190. The method of claim 189, wherein the maximum plasma concentration occurs at about 4 hours to about 6 hours after administration of the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor.

191. The method of claim 189, wherein the metabolite is abiraterone.

192. The method of claim 149, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor provides a maximum plasma concentration of the 17α

-hydroxylase/C_17,20-lyase inhibitor, or a metabolite thereof, in the patient of about 50 nmol/L to about 5000 nmol/L.

193. The method of claim 192, wherein the maximum plasma concentration is about 250 nmol/L to about 4000 nmol/L.

194. The method of claim 192, wherein the maximum plasma concentration is about 200 nmol/L to about 2500 nmol/L.

195. The method of claim 192, wherein the metabolite is abiraterone.

196. The method of claim 149, wherein the therapeutically effective amount of the 17α

-hydroxylase/C_17,20-lyase inhibitor provides an area under the curve of a plot of plasma concentration of the 17α

-hydroxylase/C_17,20-lyase inhibitor, or a metabolite thereof, versus time of about 50 hr*nmol/L to about 25,000 hr*nmol/L.

197. The method of claim 196, wherein the area under the curve is about 1,000 hr*nmol/L to about 20,000 hr*nmol/L.

198. The method of claim 197, wherein the area under the curve is about 5,000 hr*nmol/L to about 18,000 hr*nmol/L.

199. A method for the treatment of a patient having prostate cancer comprising administering to the patient having prostate cancer that is refractory to a chemotherapy a therapeutically effective amount of abiraterone acetate, wherein the therapeutically effective amount is about 800 mg/day to about 2,000 mg/day, and wherein the maximum plasma concentration of the abiraterone acetate or a metabolite thereof in the patient is about 50 nmol/L to about 5000 nmol/L.

200. A method for the treatment of a patient having prostate cancer comprising administering to the patient having prostate cancer that is refractory to a hormone therapy a therapeutically effective amount of abiraterone acetate, wherein the therapeutically effective amount is about 800 mg/day to about 2,000 mg/day, and wherein the maximum plasma concentration of the abiraterone acetate or a metabolite thereof in the patient is about 50 nmol/L to about 5000 nmol/L.

201. A method for the treatment of a patient having prostate cancer comprising administering to the patient having prostate cancer that is refractory to a chemotherapy and refractory to a hormone therapy a therapeutically effective amount of abiraterone acetate, wherein the therapeutically effective amount is about 800 mg/day to about 2,000 mg/day, and wherein the maximum plasma concentration of the abiraterone acetate or a metabolite thereof in the patient is about 50 nmol/L to about 5000 nmol/L.

202. A method for the treatment of a patient having prostate cancer comprising administering to the patient having prostate cancer that is refractory to a chemotherapy a therapeutically effective amount of abiraterone acetate, wherein the therapeutically effective amount is about 800 mg/day to about 2,000 mg/day, and wherein the maximum plasma concentration of abiraterone acetate or a metabolite thereof in the patient occurs at about 1 hour to about 8 hours after administration of the therapeutically effective amount of abiraterone acetate.

203. A method for the treatment of a patient having prostate cancer comprising administering to the patient having prostate cancer that is refractory to a hormone therapy a therapeutically effective amount of abiraterone acetate, wherein the therapeutically effective amount is about 800 mg/day to about 2,000 mg/day, and wherein the maximum plasma concentration of abiraterone acetate or a metabolite thereof in the patient occurs at about 1 hour to about 8 hours after administration of the therapeutically effective amount of abiraterone acetate.

204. A method for the treatment of a patient having prostate cancer comprising administering to the patient having prostate cancer that is refractory to a chemotherapy and refractory to a hormone therapy a therapeutically effective amount of abiraterone acetate, wherein the therapeutically effective amount is about 800 mg/day to about 2,000 mg/day, and wherein the maximum plasma concentration of abiraterone acetate or a metabolite thereof in the patient occurs at about 1 hour to about 8 hours after administration of the therapeutically effective amount of abiraterone acetate.

205. A method for the treatment of a patient having prostate cancer comprising administering to the patient having prostate cancer that is refractory to a chemotherapy a therapeutically effective amount of abiraterone acetate, wherein the patient has been castrated prior to administration of the therapeutically effective amount of abiraterone acetate, and wherein the prostate cancer has metastasized.

206. A method for the treatment of a patient having prostate cancer comprising administering to the patient having prostate cancer that is refractory to a hormone therapy a therapeutically effective amount of abiraterone acetate, wherein the patient has been castrated prior to administration of the therapeutically effective amount of abiraterone acetate, and wherein the prostate cancer has metastasized.

207. A method for the treatment of a patient having prostate cancer comprising administering to the patient having prostate cancer that is refractory to a chemotherapy and refractory to a hormone therapy a therapeutically effective amount of abiraterone acetate, wherein the patient has been castrated prior to administration of the therapeutically effective amount of abiraterone acetate, and wherein the prostate cancer has metastasized.