N-acetylcolchinol-o-phosphate combination therapies with vascular damaging activity

Abstract

The invention relates to a method for the production of a vascular damaging effect in a warm-blooded animal such as a human, which comprises administering to said animal an effective amount of ZD6126 or a pharmaceutically NHCOCH acceptable salt thereof, before, after or simultaneously with an effective amount of one of the following therapies: i) ionising radiation; ii) a platinum anti-tumour agent; and iii) a taxane. The invention also relates to the use of ZD6126 and one of the above therapies in the manufacture of a medicament for use in the production of a vascular damaging effect in a warm-blooded animal such as a human and to pharmaceutical compositions and kits each comprising ZD6126 and one of a platinum anti-tumour agent and a taxane.

1 - 10 . (canceled)  
     
     
         11 . A method for reversing neovascularisation be damaging newly-formed vascular endothelium in a warm-blooded animal in need thereof, which comprises administering to said animal an effective amount of ZD6126  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, before, after or simultaneously with an effective amount of one of the following therapies: 
 i) ionising radiation;  
 ii) a platinum anti-tumour agent; and  
 iii) a taxane.  
 
     
     
         12 . A method for reversing neovascularisation by damaging newly-formed vascular endothelium in a warm-blooded animal in need thereof, which comprises administering to said animal an effective amount of ZD6126  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, in divided doses, before, after or simultaneously with an effective amount of one of the following therapies: 
 i) ionising radiation;  
 ii) a platinum anti-tumour agent; and  
 iii) a taxane.  
 
     
     
         13 . The method according to  claim 11 , which comprises administering to said animal an effective amount of ZD6126 or a pharmaceutically acceptable salt thereof, before, after or simultaneously with an effective amount of ionising radiation.  
     
     
         14 . The method according to  claim 11 , which comprises administering to said animal an effective amount of ZD6126 or a pharmaceutically acceptable salt thereof, before, after or simultaneously with an effective amount of a platinum anti-tumour agent.  
     
     
         15 . The method according to  claim 11 , which comprises administering to said animal an effective amount of ZD6126 or a pharmaceutically acceptable salt thereof, before, after or simultaneously with an effective amount of a taxane.  
     
     
         16 . A method for the treatment of a cancer involving a solid tumour in a warm-blooded animal, which comprises administering to said animal an effective amount of ZD6126 or a pharmaceutically acceptable salt thereof, before, after or simultaneously with an effective amount of ionising radiation.  
     
     
         17 . A method for the treatment of a cancer involving a solid tumour in a warm-blooded animal, which comprises administering to said animal an effective amount of ZD6126 or a pharmaceutically acceptable salt thereof, before, after or simultaneously with an effective amount of a platinum anti-tumour agent.  
     
     
         18 . A method for the treatment of a cancer involving a solid tumour in a warm-blooded animal, which comprises administering to said animal an effective amount of ZD6126 or a pharmaceutically acceptable salt thereof, before, after or simultaneously with an effective amount of a taxane.  
     
     
         19 . The method according to  claim 12  wherein the total daily dose of ZD6126 is administered in two parts which are about equal or unequal with a time interval between doses of about 1 hour to about 6 hours.  
     
     
         20 . The method according to  claim 12  wherein the total daily dose of ZD6126 is administered in two parts which are about equal or unequal with a time interval between doses of greater than or equal to two hours and less than 5 hours.  
     
     
         21 . The method according to  claim 12  wherein the total daily dose of ZD6126 is administered in two parts which are about equal or unequal with a time interval between doses of greater than or equal to about 2 hours and less than or equal to about 4 hours.  
     
     
         22 . The method according to  claim 12  wherein the total daily dose of ZD6126 is administered in two parts which are about equal.  
     
     
         23 . The method according to any one of  claims 13  to  18  wherein the ZD6126 is administered in divided doses.  
     
     
         24 . The method according to  claim 23  wherein the total dose of ZD6126 is administered in two parts which are about equal.  
     
     
         25 . The method according to  claim 23  wherein the total daily dose of ZD6126 is administered in two parts which are about equal or unequal with a time interval between doses of about 1 hour to about 6 hours.  
     
     
         26 . The method according to  claim 23  wherein the total daily dose of ZD6126 is divided into two parts which are about equal or unequal with a time interval between doses of greater than or equal to two hours and less than 5 hours.  
     
     
         27 . The method according to  claim 23  wherein the total daily dose of ZD6126 is divided into two parts which are about equal or unequal with a time interval between doses of greater than or equal to about 2 hours and less than or equal to about 4 hours.  
     
     
         28 . A combination treatment that produces an anti tumour effect in a warm-blooded animal, which comprises administering to a warm-blooded animal in need of said treatment an effective amount of ZD6126 or a pharmaceutically acceptable salt thereof, optionally together with a pharmaceutically acceptable excipient or carrier, and the simultaneous, sequential or separate administration of an effective amount of one of: 
 i) ionising radiation;    ii) a platinum anti-tumour agent; and    iii) a taxane;    wherein a platinum anti-tumour agent and a taxane may each optionally be administered together with a pharmaceutically acceptable excipient or carrier.    
     
     
         29 . A combination treatment that produces an anti tumour effect in a warm-blooded animal, which comprises administering to a warm-blooded animal in need of said treatment an effective amount of ZD6126 or a pharmaceutically acceptable salt thereof, optionally together with a pharmaceutically acceptable excipient or carrier, and the simultaneous, sequential or separate administration of an effective amount of ionising radiation.  
     
     
         30 . A combination treatment that produces an anti tumour effect in a warm-blooded animal, which comprises administering to a warm-blooded animal in need of said treatment an effective amount of ZD6126 or a pharmaceutically acceptable salt thereof, optionally together with a pharmaceutically acceptable excipient or carrier, and the simultaneous, sequential or separate administration of an effective amount of a platinum anti-tumour agent; wherein said platinum anti-tumour agent is optionally administered together with a pharmaceutically acceptable excipient or carrier.  
     
     
         31 . A combination treatment that produces an anti tumour effect in a warm-blooded animal, which comprises administering to a warm-blooded animal in need of said treatment an effective amount of ZD6126 or a pharmaceutically acceptable salt thereof, optionally together with a pharmaceutically acceptable excipient or carrier, and the simultaneous, sequential or separate administration of an effective amount of a taxane; wherein said taxane is optionally administered together with a pharmaceutically acceptable excipient or carrier.  
     
     
         32 . The combination treatment according to any one of  claims 28  to  31  wherein the ZD6126 is administered in divided doses.  
     
     
         33 . The combination treatment according to  claim 32  wherein the total daily dose of ZD6126 is administered in two parts which are about equal.  
     
     
         34 . The combination treatment according to  claim 32  wherein the total daily dose of ZD6126 is administered in two parts which are about equal or unequal with a time interval between doses of about 1 hour to about 6 hours.  
     
     
         35 . The combination treatment according to  claim 32  wherein the total daily dose of ZD6126 is administered in two parts which are about equal or unequal with a time interval between doses of greater than or equal to two hours and less than 5 hours.  
     
     
         36 . The combination treatment according to  claim 32  wherein the total daily dose of ZD6126 is administered in two parts which are about equal or unequal with a time interval between doses of greater than or equal to about 2 hours and less than or equal to about 4 hours.  
     
     
         37 . The method according to any one of claims  11 ,  12 ,  14 ,  17 ,  19 ,  20 ,  21  or  22  wherein the administered therapy is a platinum anti-tumour agent, which is selected from cisplatin, carboplatin, oxaliplatin and (SP-4-3)-(cis-amminedichloro[2-methylpyridine]platinum(II).  
     
     
         38 . The method according  claim 37  wherein the platinum anti-tumour agent is cisplatin.  
     
     
         39 . The method according to  claim 14  or  claim 17  wherein the ZD6126 is administered in divided doses and the platinum anti-tumour agent is selected from cisplatin, carboplatin, oxaliplatin and (SP-4-3)-(cis-amminedichloro[2-methylpyridine]platinum(II).  
     
     
         40 . The method according to any one of claims  11 ,  12 ,  15 ,  18 ,  19 ,  20 ,  21  or  22  wherein the administered therapy is taxane, which is selected from paclitaxel and docetaxel.  
     
     
         41 . The method according to  claim 40  wherein the taxane is paclitaxel.  
     
     
         42 . The method according to  claim 15  or  claim 18  wherein the ZD6126 is administered in divided doses and the taxane is selected from paclitaxel and docetaxel.