Combination therapies for treatment of cancer

Abstract

Combination therapies for treatment of cancer are provided. The disclosed methods comprise administration of a cyclin-dependent kinase inhibitor and a DNA methyltransferase inhibitor to a mammal in need thereof.

1 . A method for treating myelodysplastic syndrome (MDS) in a mammal in need thereof, the method comprising administering to the mammal a therapeutically effective amount of the following therapeutic agents:
 i) alvocidib, or a pharmaceutically acceptable salt thereof; and   ii) a DNA methyltransferase inhibitor selected from azacitidine, or a pharmaceutically acceptable salt thereof, or decitabine, or a pharmaceutically acceptable salt thereof.   
     
     
         2 - 8 . (canceled) 
     
     
         9 . The method of  claim 1 , wherein the alvocidib, or a pharmaceutically acceptable salt thereof, is administered to the mammal prior to administration of the DNA methyltransferase inhibitor. 
     
     
         10 . The method of  claim 9 , wherein the DNA methyltransferase inhibitor is administered within about 24 to 48 hours after administration of the alvocidib, or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of  claim 1 , wherein the DNA methyltransferase inhibitor is administered to the mammal prior to administration of the alvocidib, or a pharmaceutically acceptable salt thereof. 
     
     
         12 - 15 . (canceled) 
     
     
         16 . A kit comprising alvocidib, or a pharmaceutically acceptable salt thereof, a DNA methyltransferase inhibitor selected from azacitidine, or a pharmaceutically acceptable salt thereof, and decitabine, or a pharmaceutically acceptable salt thereof, and instructions for administering the alvocidib, or a pharmaceutically acceptable salt thereof, and the DNA methyltransferase inhibitor to a mammal in need of treatment for MDS. 
     
     
         17 - 19 . (canceled) 
     
     
         20 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient, alvocidib, or a pharmaceutically acceptable salt thereof, and a DNA methyltransferase inhibitor selected from azacitidine, or a pharmaceutically acceptable salt thereof, or decitabine, or a pharmaceutically acceptable salt thereof. 
     
     
         21 . The method of  claim 1 , wherein the DNA methyltransferase inhibitor is azacitidine, or a pharmaceutically acceptable salt thereof. 
     
     
         22 . The method of  claim 1 , wherein the DNA methyltransferase inhibitor is decitabine, or a pharmaceutically acceptable salt thereof. 
     
     
         23 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         24 . The kit of  claim 16 , wherein the DNA methyltransferase inhibitor is azacitidine, or a pharmaceutically acceptable salt thereof. 
     
     
         25 . The kit of  claim 16 , wherein the DNA methyltransferase inhibitor is decitabine, or a pharmaceutically acceptable salt thereof. 
     
     
         26 . The kit of  claim 16 , wherein the mammal is a human. 
     
     
         27 . The pharmaceutical composition of  claim 20 , wherein the DNA methyltransferase inhibitor is azacitidine, or a pharmaceutically acceptable salt thereof. 
     
     
         28 . The pharmaceutical composition of  claim 20 , wherein the DNA methyltransferase inhibitor is decitabine, or a pharmaceutically acceptable salt thereof.