Combination Therapy with Apalutamide
This disclosure provides a dosage regimen for co-administration of 4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide and a strong CYP3A4 inducer.
1 . A method of treating cancer, comprising co-administration to a patient in need thereof a therapeutically effective dose of 4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide and a CYP3A4 inducer, wherein the therapeutically effective dose of 4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide is 200-300 mg per day.
2 . The method of claim 1 , wherein the cancer is selected from the group consisting of prostate cancer, breast cancer, and ovarian cancer.
3 . The method of claim 1 , wherein the therapeutically effective dose of 4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide is 240 mg per day.
4 . A method of treating metastatic castration-resistant prostate cancer, comprising co-administration to a patient in need thereof (i) 240 mg/day of 4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide and (ii) a CYP3A4 inducer.
5 . The method of claim 1 , wherein the CYP3A4 inducer is selected from the group consisting of carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentine.
6 . The method of claim 4 , wherein the CYP3A4 inducer is selected from the group consisting of carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentine.