Method of Treating Cancer

Abstract

This invention is directed to the treatment of cancer, particularly castration-resistant prostate cancer and osteoblastic bone metastases, with a dual inhibitor of MET and VEGF.

1 . A method for treating castration resistant prostate cancer (CRPC), or bone cancer associated with CRPC, comprising administering a compound that dually modulates MET and VEGF to a patient in need of such treatment, wherein the compound is Compound 1: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The method of  claim 1 , wherein the bone cancer is osteoblastic bone metastases. 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein Compound 1 is N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide. 
     
     
         8 . The method of  claim 1 , wherein Compound I is the (L)- or (D)-malate salt. 
     
     
         9 . The method of  claim 1 , wherein Compound 1 is in the crystalline N-1 form of the (L) malate salt and/or the (D) malate salt. 
     
     
         10 . The method of  claim 1 , wherein Compound 1, or a pharmaceutically acceptable salt thereof, is administered as a pharmaceutical composition additionally comprising a pharmaceutically acceptable carrier, excipient, or diluent. 
     
     
         11 . A method for treating osteoblastic bone metastases associated with castration resistant prostate cancer (CRPC), comprising administering a pharmaceutical composition comprising the malate salt of Compound 1 to a patient in need of such treatment. 
     
     
         12 . A method for ameliorating abnormal deposition of unstructured bone accompanied by increased skeletal fractures, spinal cord compression, and severe bone pain of osteoblastic bone metastases, or for reducing or stabilizing metastatic bone lesions associated with castration resistant prostate cancer (CRPC), or for reducing or minimizing bone pain due to metastatic bone lesions associated with CRPC, comprising administering to a patient in need of such treatment a therapeutically effective amount of Compound 1. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . A method for preventing osteoblastic bone metastases associated with castration resistant prostate cancer (CRPC) or for preventing bone metastases in patients with prostate cancer who are castration resistant but have not yet advanced to metastatic disease, comprising administering a therapeutically effective amount of a pharmaceutical composition the malate salt of Compound 1, to a patient in need of such treatment. 
     
     
         17 . (canceled) 
     
     
         18 . A method for extending the overall survival in patients with castration resistant prostate cancer (CRPC), comprising administering a therapeutically effective amount of a pharmaceutical composition comprising Compound 1 or the malate salt of Compound 1 or another pharmaceutically acceptable salt of Compound 1, to a patient in need of such treatment.