Methods of treating cancer using aurora kinase inhibitors

Abstract

Disclosed are methods for the treatment of various cell proliferative disorders. Disclosed in particular are methods for treatment of various cell proliferative disorders by administering a selective inhibitor of Aurora A kinase in combination with taxane-based chemotherapy, such as paclitaxel or docetaxel.

1 . A method of treating a cell proliferative disorder in a subject in need thereof, comprising administering to the subject on a 28-day dose schedule a twice-daily dose of alisertib in combination with a once-weekly dose of paclitaxel, wherein
 the administered twice-daily dose of alisertib is from about 30 mg to about 50 mg, and is administered on days 1-3, 8-10, and 15-17 of the 28-day schedule; and   the administered once-weekly dose of paclitaxel is from about 40 mg/m 2  to about 80 mg/m 2 , and is administered on days 1, 8, and 15 of the 28-day schedule.   
     
     
         2 . The method of  claim 1 , wherein the administration of alisertib is concomitant with the administration of paclitaxel. 
     
     
         3 . The method of  claim 1 , wherein the twice-daily dose of alisertib is from about 40 mg to about 50 mg. 
     
     
         4 . The method of  claim 1 , wherein the twice-daily dose of alisertib is from about 30 mg to about 40 mg. 
     
     
         5 . The method of  claim 1 , wherein the twice-daily dose of alisertib is about 35 mg. 
     
     
         6 . The method of  claim 1 , wherein the twice-daily dose of alisertib is about 40 mg. 
     
     
         7 . The method of  claim 1 , wherein the twice-daily dose of alisertib is about 45 mg. 
     
     
         8 . The method of  claim 1 , wherein the once-weekly dose of paclitaxel is from about 60 mg/m 2  to about 70 mg/m 2 . 
     
     
         9 . The method of  claim 1 , wherein the once-weekly dose of paclitaxel is about 60 mg/m 2 . 
     
     
         10 . The method of  claim 1 , wherein the cell proliferative disorder is cancer. 
     
     
         11 . The method of  claim 10 , wherein the cancer is ovarian cancer, breast cancer, prostate cancer, gastric cancer, head and neck cancer, bladder cancer, lung cancer or AIDS-related Kaposi's sarcoma. 
     
     
         12 . The method of  claim 10 , wherein the cancer is ovarian cancer, breast cancer, lung cancer or AIDS-related Kaposi's sarcoma. 
     
     
         13 . The method of  claim 10 , wherein the cancer is ovarian cancer. 
     
     
         14 . The method of  claim 10 , wherein the cancer is small-cell lung cancer. 
     
     
         15 . A kit, comprising alisertib, or a pharmaceutically acceptable salt thereof paclitaxel, or a pharmaceutically acceptable salt thereof and instructions for administering the alisertib or a pharmaceutically acceptable salt thereof in combination with the paclitaxel, or a pharmaceutically acceptable salt thereof.