Methods for treating cancer
Disclosed herein are methods of inhibiting tumor growth or producing tumor regression in a subject having a drug-resistant estrogen receptor alpha positive cancer or a mutant estrogen receptor alpha positive cancer. The methods entail administering to the subject a therapeutically effective amount of RAD1901 having the structure: or a salt or solvate thereof.
1. A method of inhibiting tumor growth or producing tumor regression in a subject having a mutant estrogen receptor alpha positive breast cancer comprising administering to said subject a therapeutically effective amount of RAD1901 having the structure:
or a salt or solvate thereof.
2. The method of claim 1 , wherein the mutant estrogen receptor alpha positive breast cancer is drug resistant.
3. The method of claim 1 , wherein the breast cancer is a metastatic cancer.
4. The method of claim 1 , wherein said breast cancer is positive for the mutant estrogen receptor alpha comprising one or more mutations selected from the group consisting of Y537X 1 , L536X 2 , P535H, V534E, S463P, V392I, D538G, E380Q and combinations thereof, wherein:
X 1 is S, N, or C; and X 2 is R or Q.
5. The method of claim 4 , wherein the mutation is Y537S.
6. The method of claim 1 , wherein the ratio of the concentration of RAD1901 or a salt or solvate thereof in the tumor to the concentration of RAD1901 or a salt or solvate thereof in plasma (T/P) following administration is at least about 15.
7. The method of claim 1 , wherein subject has osteoporosis or a high risk of osteoporosis.
8. The method of claim 1 , wherein the subject is a pre-menopausal woman.
9. The method of claim 1 , wherein the subject is a post-menopausal woman who had relapsed or progressed after previous treatment with SERMs and/or AIs.
10. The method of claim 1 , wherein the therapeutically effective amount is about 150 to about 1,500 mg q.d.
11. The method of claim 1 , wherein the salt thereof is RAD1901 dihydrochloride.
12. The method of claim 1 , wherein the tumor is resistant to, or progresses over, a drug selected from the group consisting of anti-estrogens, aromatase inhibitors, and combinations thereof.
13. The method of claim 12 , wherein the anti-estrogen is tamoxifen or fulvestrant.
14. The method of claim 12 , wherein the aromatase inhibitor is aromasin.
15. The method of claim 1 , wherein the therapeutically effective amount is 150 mg to 2,000 mg.
16. The method of claim 15 , wherein the therapeutically effective amount is 200 mg, 400 mg, or 500 mg.
17. A method of inhibiting tumor growth or producing tumor regression in a subject having a mutant estrogen receptor alpha positive breast cancer consisting of administering to said subject a therapeutically effective amount of RAD1901 having the structure:
or a salt or solvate thereof.
18. A method of inhibiting tumor growth or producing tumor regression in a subject having a mutant estrogen receptor alpha positive breast cancer comprising administering to said subject a therapeutically effective amount of RAD1901 alone, RAD1901 having the structure:
or a salt or solvate thereof.
19. The method of claim 17 , wherein the mutant estrogen receptor alpha comprises the mutation Y537S.
20. The method of claim 18 , wherein the mutant estrogen receptor alpha comprises the mutation Y537S.