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 estrogen receptor alpha-positive cancer that has a mutant estrogen receptor alpha comprising administering to said subject a therapeutically effective amount of RAD1901 having the structure:
or a salt or solvate thereof.
2 . (canceled)
3 . The method of claim 1 , wherein the cancer is breast cancer.
4 . The method of claim 3 , wherein the cancer is a metastatic breast cancer.
5 . The method of claim 3 , wherein said cancer is positive for the mutant estrogen receptor alpha comprising one or more mutations selected from the group consisting of Y537X1, L536X2, P535H, V534E, S463P, V392I, E380Q and combinations thereof, wherein:
X1 is S, N, or C, D538G; and X2 is R or Q.
6 . The method of claim 5 , wherein the mutation is Y537S.
7 . The method of claim 3 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.
8 . The method of claim 3 wherein said subject has osteoporosis or a high risk of osteoporosis.
9 . The method of claim 3 wherein the subject is a pre-menopausal woman.
10 . The method of claim 3 wherein the subject is a post-menopausal woman who had relapsed or progressed after previous treatment with SERMs and/or AIs.
11 . The method of claim 3 wherein the therapeutically effective amount is about 150 to about 1,500 mg q.d.
12 . The method of claim 3 , wherein the salt thereof is RAD1901 dihydrochloride.
13 . The method of claim 4 , wherein the tumor is resistant to a drug selected from the group consisting of anti-estrogens, aromatase inhibitors, and combinations thereof.
14 . The method of claim 13 , wherein the anti-estrogen is tamoxifen or fulvestrant.
15 . The method of claim 13 , wherein the aromatase inhibitor is anastrozole, letrozole or aromasin.
16 . The method of claim 3 wherein the therapeutically effective amount is 150 mg to 2,000 mg.
17 . The method of claim 3 , wherein the therapeutically effective amount is 200 mg, 400 mg, or 500 mg.