Formulations of histone deacetylase inhibitor and uses thereof

Abstract

Dosing regimens, methods of treatment, controlled release formulations, and combination therapies that include an HDAC inhibitor, or a pharmaceutically acceptable salt thereof, are described.

What is claimed is: 
     
         1 - 28 . (canceled) 
     
     
         29 . A method of treating a cancer in a human patient, comprising administering to the patient a therapeutically-effective amount of Compound 1 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically-acceptable salt thereof, and
 administering to the patient a therapeutically-effective amount of an anti-angiogenic agent. 
 
     
     
         30 . The method of  claim 29 , wherein the cancer is a carcinoma, a sarcoma, a lymphoma, or a leukemia. 
     
     
         31 . The method of  claim 29 , wherein the cancer is a carcinoma. 
     
     
         32 . The method of  claim 29 , wherein the cancer is selected from breast cancer, colon cancer, colorectal carcinomas, non-small cell lung cancer, small-cell lung cancer, kidney cancer, bladder and urethra cancer, liver cancer, ovarian cancer, prostate cancer, uterine cervix cancer, urinary bladder cancer, gall bladder carcinoma, gastric carcinoma, esophageal cancer, gastrointestinal stromal tumor, pancreatic cancer, germ cell tumors, mast cell tumors, neuroblastoma, retinoblastoma, mesothelioma, mastocytosis, testicular cancers, glioblastomas, astrocytomas, sarcoma, osteosarcoma, B cell lymphoma, T cell lymphoma, NK cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, melanoma, basal cell carcinoma, skin cancer, myeloma, leukemia, acute myelocytic leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome, chronic lymphocytic leukemia (CLL) and chronic myelogenous leukemia (CML). 
     
     
         33 . The method of  claim 29 , wherein the cancer is selected from kidney cancer. 
     
     
         34 . The method of  claim 29 , wherein the cancer is selected from kidney adenocarcinoma and nephroblastoma. 
     
     
         35 . The method of  claim 29 , wherein the anti-angiogenic agent is selected from axitinib, bevacizumab, lenalidomide, sorafenib, sunitinib malate, thalidomide, and vandetanib. 
     
     
         36 . The method of  claim 29 , wherein administering to the patient a therapeutically effective amount of compound 1 comprises orally administering a first dose of compound 1 and orally administering a second dose of compound 1, wherein the two doses are administered within the same day. 
     
     
         37 . The method of  claim 36 , wherein the second dose is administered about 4 to about 6 hours after the first dose. 
     
     
         38 . The method of  claim 36 , wherein the first and second doses together comprise a total daily dose of from 10 mg/m 2  to 200 mg/m 2  of Compound 1. 
     
     
         39 . The method of  claim 38 , wherein the first and second doses together comprise a total daily dose of from 30 mg/m 2  to 90 mg/m 2  of Compound 1. 
     
     
         40 . The method of  claim 38 , wherein the first dose is administered as a formulation that includes about 30 mg/m 2 , about 40 mg/m 2 , about 50 mg/m 2 , or about 60 mg/m 2  of Compound 1; and the second dose is administered as a formulation that includes about 30 mg/m 2 , about 40 mg/m 2 , about 50 mg/m 2 , or about 60 mg/m 2  of Compound 1. 
     
     
         41 . The method of  claim 39 , wherein the total daily dose is about 60 mg/m 2  or about 90 mg/m 2  of Compound 1. 
     
     
         42 . The method of  claim 36 , wherein administering a therapeutically effective amount of Compound 1 comprises maintaining an effective plasma concentration of the HDAC inhibitor for at least 6 consecutive hours. 
     
     
         43 . The method of  claim 36 , further comprising orally administering a third dose of Compound 1, wherein the first dose, the second dose and the third dose are administered consecutively about 4 to 6 hours apart.