Method of Treating Cancer and Bone Cancer Pain

Abstract

This invention is directed to the treatment of cancer, particularly lung cancer, breast cancer, melanoma, renal cell carcinoma, thyroid cancer that has metastasized to the bone. The invention is also directed to a method for treating bone cancer pain in an individual in need of such treatment comprising administering to the individual an effective amount of a compound of Formula I.

1 . A method for treating bone cancer associated with breast cancer, melanoma, renal cell carcinoma, sarcoma, lung cancer, or thyroid cancer, comprising administering to a patient in need of such treatment a compound of Formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is halo; 
 R 2  is halo; 
 R 3  is (C 1 -C 6 )alkyl; 
 R 4  is (C 1 -C 6 )alkyl; and 
 Q is CH or N. 
 
       
     
     
         2 . The method of  claim 1 , wherein the dual MET and VEGF modulator is a compound of Formula Ia 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein:
 R 1  is halo; 
 R 2  is halo; and 
 Q is CH or N. 
 
       
     
     
         3 . The method of  claims 1 - 2 , wherein the compound of Formula I is compound I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         4 . The compound of  claim 3 , which is N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide. 
     
     
         5 . The method of  claims 1 - 4 , wherein the compound of Formula (I), Formula I(a) and Compound 1 is the (L)- or (D)-malate salt. 
     
     
         6 . The method of  claims 1 - 5 , wherein the compound of Formula (I) is in the crystalline N-1 form of the (L) malate salt and/or the (D) malate salt. 
     
     
         7 . The method of  claim 1 , wherein the bone cancer is bone metastases from lung cancer, breast cancer, melanoma, renal cell carcinoma, or thyroid cancer. 
     
     
         8 . A method for ameliorating abnormal deposition of unstructured bone accompanied by increased skeletal fractures, spinal cord compression, and severe bone pain of bone metastases, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of  claims 2 - 6 , optionally as a pharmaceutical composition. 
     
     
         9 . A method for reducing or stabilizing metastatic bone lesions associated with lung cancer, breast cancer, melanoma, renal cell carcinoma, or thyroid cancer, comprising administering a therapeutically effective amount of a compound  claims 2 - 6 , optionally as a pharmaceutical composition, to a patient in need of such treatment. 
     
     
         10 . A method for reducing, treating or minimizing bone pain due to metastatic bone lesions associated with lung cancer, breast cancer, melanoma, renal cell carcinoma, or thyroid cancer, comprising administering a therapeutically effective amount of a compound of  claims 2 - 6 , optionally as a pharmaceutical composition, to a patient in need of such treatment. 
     
     
         11 . A method for preventing bone metastases associated with lung cancer, breast cancer, melanoma, renal cell carcinoma, or thyroid cancer, comprising administering a therapeutically effective amount of a pharmaceutical formulation comprising  claims 2 - 6 , optionally as a pharmaceutical composition, to a patient in need of such treatment. 
     
     
         12 . A method for extending the overall survival in patients with lung cancer, breast cancer, melanoma, renal cell carcinoma, or thyroid cancer metastasized to bone, comprising administering a therapeutically effective amount of  claims 2 - 6 , optionally as a pharmaceutical composition, to a patient in need of such treatment. 
     
     
         13 . A method for treating bone cancer pain in an individual in need of such treatment comprising administering to the individual an effective amount of a compound of  claims 2 - 6 , optionally as a pharmaceutical composition. 
     
     
         14 . The method of  claim 13 , wherein the bone cancer pain is from cancer originated in bone. 
     
     
         15 . The method of  claim 13 , wherein the bone cancer pain is from osteosarcoma. 
     
     
         16 . The method of  claim 13 , wherein the bone cancer pain is from cancer metastasized to bone. 
     
     
         17 . The method of  claim 13 , wherein the bone cancer pain is from breast cancer metastasized to bone. 
     
     
         18 . The method of  claim 17 , wherein the bone cancer pain is from lung cancer metastasized to bone. 
     
     
         19 . The method of  claim 13 , wherein the bone cancer pain is from sarcoma metastasized to bone. 
     
     
         20 . The method of  claim 13 , wherein the bone cancer pain is from renal cancer metastasized to bone. 
     
     
         21 . The method of  claim 13 , wherein the bone cancer pain is from thyroid cancer metastasized to bone. 
     
     
         22 . The method of  claim 13 , wherein the bone cancer pain is from melanoma metastasized to bone.