Antineoplastic combinations

Abstract

This invention provides the use of a combination of CCI-779 and EKB-569 in the treatment of neoplasms.

1. A method of treating a neoplasm in a mammal in need thereof, which comprises providing to said mammal synergistically effective amount of a combination comprising CCI-779 and EKB-569. 
     
     
       2. The method according to  claim 1 , wherein the neoplasm is renal cancer. 
     
     
       3. The method according to  claim 1 , wherein the neoplasm is soft tissue sarcoma. 
     
     
       4. The method according to  claim 1 , wherein the neoplasm is breast cancer. 
     
     
       5. The method according to  claim 1 , wherein the neoplasm is a neuroendocrine tumor of the lung. 
     
     
       6. The method according to  claim 1 , wherein the neoplasm is cervical cancer. 
     
     
       7. The method according to  claim 1 , wherein the neoplasm is uterine cancer. 
     
     
       8. The method according to  claim 1 , wherein the neoplasm is a head and neck cancer. 
     
     
       9. The method according to  claim 1 , wherein the neoplasm is glioma. 
     
     
       10. The method according to  claim 1 , wherein the neoplasm is non-small cell lung cancer. 
     
     
       11. The method according to  claim 1 , wherein the neoplasm is prostate cancer. 
     
     
       12. The method according to  claim 1 , wherein the neoplasm is pancreatic cancer. 
     
     
       13. The method according to  claim 1 , wherein the neoplasm is lymphoma. 
     
     
       14. The method according to  claim 1 , wherein the neoplasm is melanoma. 
     
     
       15. The method according to  claim 1 , wherein the neoplasm is small cell lung cancer. 
     
     
       16. The method according to  claim 1 , wherein the neoplasm is ovarian cancer. 
     
     
       17. The method according to  claim 1 , wherein the neoplasm is colon cancer. 
     
     
       18. The method according to  claim 1 , wherein the neoplasm is esophageal cancer. 
     
     
       19. The method according to  claim 1 , wherein the neoplasm is gastric cancer. 
     
     
       20. The method according to  claim 1 , wherein the neoplasm is leukemia. 
     
     
       21. The method according to  claim 1 , wherein the neoplasm is colorectal cancer. 
     
     
       22. The method according to  claim 1 , wherein the neoplasm is unknown primary cancer. 
     
     
       23. A method of treating a neoplasm in a mammal in need thereof, which comprises providing to said mammal an effective amount of a synergistic combination comprising CCI-779 and EKB-569, wherein either CCI-779, EKB-569, or both are provided in subtherapeutically effective amounts. 
     
     
       24. The method according to  claim 23  in which CCI-779 is provided in a subtherapeutically effective amount. 
     
     
       25. The method according to  claim 23  in which EKB-569 is provided in a subtherapeutically effective amount. 
     
     
       26. The method according to  claim 23  in which both CCI-779 and EKB-569 are provided in subtherapeutically effective amounts. 
     
     
       27. An antineoplastic combination which comprises an antineoplastic effective amount of a synergistic combination of CCI-779 and EKB-569. 
     
     
       28. A process for the preparation of a compound of formula:
                   
       
         comprising:  
         ( a )  reacting a trimethylsilyl -   4   - bromocrotonate or methyl  4   - bromocrotonate with dimethylamine to obtain the corresponding  4   - dimethylaminocrotonate;    
         ( b )  hydrolyzing the  4   - dimethylaminocrotonate of step  ( a )  to form the corresponding  4   - dimethylaminocrotonic acid; and    
         ( c )  optionally chlorinating the compound of step  ( b )  to form the HCl salt of the compound of step  ( b ). 
       
     
     
       29. The process according to  claim 28 , wherein the hydrolyzing step ( c )  comprises reacting the  4   - dimethylaminocrotonate with NaOH in the presence of MeOH.   
     
     
       30. The process according to  claim 28 , wherein the chlorinating step ( c )  comprises reacting the  4   - dimethylaminocrotonic acid with HCl.   
     
     
       31. The process according to  claim 28  wherein the reaction is performed with trimethylsilyl-   4   - bromocrotonate.   
     
     
       32. The process according to  claim 28  wherein the reaction is performed with methyl  4 - bromocrotonate.