Methods of Inducing Terminal Differentiation

Abstract

The present invention provides methods of selectively inducing terminal differentiation, cell growth arrest and/or apoptosis of neoplastic cells, and/or inhibiting histone deacetylase (HDAC) by administration of pharmaceutical compositions comprising potent HDAC inhibitors. The oral bioavailability of the active compounds in the pharmaceutical compositions of the present invention is surprisingly high. Moreover, the pharmaceutical compositions unexpectedly give rise to high, therapeutically effective blood levels of the active compounds over an extended period of time. The present invention further provides a safe, daily dosing regimen of these pharmaceutical compositions, which is easy to follow, and which results in a therapeutically effective amount of the HDAC inhibitors in vivo.

What is claimed is: 
     
         1 . A method of treating a hematological malignacy in a patient, comprising orally administering to said patient a single dose of 400 mg daily of suberoylanilide hydroxamic acid (SAHA) represented by the following structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or hydrate thereof. 
       
     
     
         2 . The method of  claim 1 , wherein suberoylanilide hydroxamic acid (SAHA) is administered. 
     
     
         3 . A method of treating a hematological malignacy in a patient, comprising orally administering to said patient 200 mg twice daily of suberoylanilide hydroxamic acid (SAHA) represented by the following structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or hydrate thereof. 
       
     
     
         4 . The method of  claim 3 , wherein suberoylanilide hydroxamic acid (SAHA) is administered.