Method of treating cancer using selective estrogen receptor modulators
View Patent ↗Disclosed herein are methods of treating subjects suffering from estrogen receptor positive cancer of the brain by administering a selective estrogen receptor degrader (SERM). Also disclosed are methods of treating a cancer that is resistant to an estrogen receptor modulator by administering a SERM.
1. A method of treating breast cancer brain metastasis in a subject, the method comprising administering a compound of (R)-6-{2-{ethyl[4-(2-ethylaminoethyl)benzyl]amino}-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-ol, wherein the breast cancer brain metastasis is resistant to an estrogen receptor modulator.
2. The method of claim 1 , wherein an effective amount of the compound is administered.
3. The method of claim 2 , wherein the effective amount comprises a high dosage.
4. The method of claim 3 , wherein the high dosage is more than about 20 mg/kg.
5. The method of claim 3 , wherein the high dosage is about 20 mg/kg to about 100 mg/kg.
6. The method of claim 1 , wherein the compound is administered by oral administration, intravenous administration, intradermal injection, intramuscular injection or subcutaneous injection.
7. The method of claim 1 , further comprising administering an effective amount of at least one compound selected from the group consisting of a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6 inhibitor), an antiestrogen, a ligand of retinoic acid or retinoxic X receptor, an antiprogestin, an antiandrogen, vitamin D or metabolite thereof, a farnesyl transferase inhibitor, a PPARα or gamma agonist and a MAP kinase inhibitor.
8. The method of claim 1 , wherein the breast cancer brain metastasis is de novo resistant to the estrogen receptor modulator.
9. The method of claim 1 , wherein the resistance to the estrogen receptor modulator is acquired.
10. The method of claim 1 , wherein the estrogen receptor modulator is a selective estrogen receptor modulator (SERM).
11. The method of claim 10 , wherein the SERM is tamoxifen, idoxifene, raloxifene or ICI 182,780.
12. The method of claim 1 , wherein the estrogen receptor modulator is an aromatase inhibitor.
13. The method of claim 12 , wherein the aromatase inhibitor is anastrozole, letrozole or exemestane.
14. A method of treating breast cancer brain metastasis in a subject, the method comprising administering a composition comprising (R)-6-{2-{ethyl[4-(2-ethylaminoethyl)benzyl]amino}-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-ol, wherein the breast cancer brain metastasis is resistant to an estrogen receptor modulator.
15. The method of claim 14 , wherein the breast cancer brain metastasis is estrogen receptor positive.
16. The method of claim 14 , wherein an effective amount of the composition is administered.
17. The method of claim 16 , wherein the effective amount comprises a high dosage.
18. The method of claim 17 , wherein the high dosage is more than about 20 mg/kg.
19. The method of claim 17 , wherein the high dosage is about 20 mg/kg to about 100 mg/kg.
20. The method of claim 14 , wherein the composition is administered by oral administration, intravenous administration, intradermal injection, intramuscular injection or subcutaneous injection.
21. The method of claim 14 , further comprising administering an effective amount of at least one compound selected from the group consisting of a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6 inhibitor), an antiestrogen, a ligand of retinoic acid or retinoxic X receptor, an antiprogestin, an antiandrogen, vitamin D or metabolite thereof, a farnesyl transferase inhibitor, a PPARα or gamma agonist and a MAP kinase inhibitor.
22. The method of claim 14 , wherein the breast cancer brain metastasis is de novo resistant to the estrogen receptor modulator.
23. The method of claim 14 , wherein the resistance to the estrogen receptor modulator is acquired.
24. The method of claim 14 , wherein the estrogen receptor modulator is a selective estrogen receptor modulator (SERM).
25. The method of claim 24 , wherein the SERM is tamoxifen, idoxifene, raloxifene or ICI 182,780.
26. The method of claim 14 , wherein the estrogen receptor modulator is an aromatase inhibitor.
27. The method of claim 26 , wherein the aromatase inhibitor is anastrozole, letrozole or exemestane.
28. The method of claim 1 , wherein the breast cancer brain metastasis is estrogen receptor positive.