Antitumor combinations containing a VEGF-inhibiting agent and 5FU or a derivative thereof

Abstract

This invention relates to antitumor combinations comprising a VEGF inhibitor combined with 5-fluorouracil or with a 5-fluoropyrimidine derivative that are therapeutically useful in the treatment of neoplastic diseases, and pharmaceutical compositions comprising such combinations.

1 . A pharmaceutical composition comprising a pharmaceutically effective amount of a VEGF inhibitor and a pharmaceutically effective amount of 5-fluorouracil, and a pharmaceutically acceptable excipient.  
   
   
       2 . A pharmaceutical composition comprising a pharmaceutically effective amount of a VEGF inhibitor and a pharmaceutically effective amount 5-fluoropyrimidine derivative, and a pharmaceutically acceptable excipient.  
   
   
       3 . A method of treating a neoplastic disease, in a patient in need of such treatment, comprising administering to such patient a pharmaceutically effective amount of a combination of a VEGF inhibitor and 5-fluorouracil.  
   
   
       4 . A method of treating a neoplastic disease, in a patient in need of such treatment, comprising administering to such patient a pharmaceutically effective amount of a combination of a VEGF inhibitor and a 5-fluoropyrimidine derivative.  
   
   
       5 . A pharmaceutical composition according to  claim 2  wherein the 5-fluoropyrimidine derivative is capecitabine or gemcitabine.  
   
   
       6 . A method according to  claim 4  wherein the 5-fluoropyrimidine derivative is capecitabine or gemcitabine.  
   
   
       7 . A method according to either of claims  3  or  4 , wherein the VEGF inhibitor is VEGF-Trap.  
   
   
       8 . A pharmaceutical composition according to either of claims  1  or  2  wherein the VEGF inhibitor is VEGF-Trap.  
   
   
       9 . A pharmaceutical composition according to  claim 5  wherein the VEGF inhibitor is VEGF-Trap.  
   
   
       10 . A method according to  claim 6  wherein the VEGF inhibitor is VEGF-Trap.  
   
   
       11 . A pharmaceutical composition according to either of claims  1  or  2 , further comprising folinic acid.  
   
   
       12 . A method according to either of claims  3  or  4 , further comprising administering a pharmaceutically effective amount of folinic acid.  
   
   
       13 . A method according to  claim 3  wherein the VEGF inhibitor and 5-fluorouracil are administered simultaneously.  
   
   
       14 . A method according to  claim 3  wherein the VEGF inhibitor and 5-flourouracil are administered separately.  
   
   
       15 . A method according to  claim 4  wherein the VEGF inhibitor and the 5-fluoropyrimidine inhibitor are administered simultaneously.  
   
   
       16 . A method according to  claim 4  wherein the VEGF inhibitor and the 5-fluoropyrimidine inhibitor are administered separately.  
   
   
       17 . A pharmaceutical composition according to  claim 1  wherein the VEGF inhibitor is VEGF-Trap, and wherein the VEGF-Trap is present in the amount of 2% to 80% by weight of the total weight of VEGF-Trap and 5-fluorouracil.  
   
   
       18 . A pharmaceutical composition according to  claim 2  wherein the VEGF inhibitor is VEGF-Trap, and wherein the VEGF-Trap is present in the amount of 2% to 80% by weight of the total weight of VEGF-Trap and the 5-fluoropyrimidine derivative.  
   
   
       19 . A method according to  claim 3  wherein the VEGF inhibitor is VEGF-Trap, and wherein the VEGF-Trap is administered in an amount of 2% to 80% by weight of the total weight of VEGF-Trap and 5-fluorouracil.  
   
   
       20 . A method according to  claim 4  wherein the VEGF inhibitor is VEGF-Trap, and wherein VEGF-Trap is administered in an amount of 2% to 80% by weight of the total weight of VEGF-Trap and the 5-fluoropyrimidine derivative.  
   
   
       21 . A pharmaceutical composition according to  claim 1 , further comprising folinic acid, provided that no other chemotoxic derivative is present, and which exhibits a therapeutically synergistic effect in the treatment of neoplastic disease.  
   
   
       22 . A pharmaceutical composition according to  claim 2 , further comprising folinic acid, provided that no other chemotoxic derivative is present, and which exhibits a therapeutically synergistic effect in the treatment of neoplastic disease.  
   
   
       23 . A method according to  claim 3 , further comprising administering a pharmaceutically effective amount of folinic acid, provided that no other chemotoxic derivative is administered, and wherein the amounts of the VEGF inhibitor, 5-fluorouracil and folinic acid administered exhibit a therapeutically synergistic effect in the treatment of the neoplastic disease.  
   
   
       24 . A method according to  claim 4 , further comprising administering a pharmaceutically effective amount of folinic acid, provided that no other chemotoxic derivative is administered, and wherein the amounts of the VEGF inhibitor, the 5-fluoropyrimidine derivative and folinic acid administered exhibit a therapeutically synergistic effect in the treatment of the neoplastic disease.  
   
   
       25 . Combinations containing a VEGF inhibitor with at least 5-fluorouracil or a 5-fluoropyrimidine derivative that is therapeutically useful in the treatment of neoplastic diseases.  
   
   
       26 . Combinations containing a VEGF inhibitor with 5-fluorouracil or capecitabine or gemcitabine.  
   
   
       27 . The combinations as claimed in  claim 26 , containing a VEGF inhibitor with fluorouracil.  
   
   
       28 . The combinations as claimed in  claim 27 , containing a VEGF-Trap inhibitor with 5-fluorouracil.  
   
   
       29 . The combinations as claimed in any one of  claims 25  to  28 , which also contain folinic acid.  
   
   
       30 . The combinations as claimed in one of  claims 25  to  28 , which contain from 2 to 80% by weight of VEGF-Trap.  
   
   
       31 . The combinations as claimed in  claim 25 , which also contain folinic acid, and which contain from 2 to 80% of VEGF-Trap.  
   
   
       32 . The combinations as claimed in  claim 26 , which also contain folinic acid, and which contain from 2 to 80% of VEGF-Trap.  
   
   
       33 . The combinations as claimed in  claim 27 , which also contain folinic acid, and which contain from 2 to 80% of VEGF-Trap.  
   
   
       34 . The combinations as claimed in  claim 28 , which also contain folinic acid, and which contain from 2 to 80% of VEGF-Trap.  
   
   
       35 . Products containing a VEGF inhibitor and at least one therapeutically useful substance as defined in one of  claims 25  to  28 , in the treatment of neoplastic diseases, as a combined preparation for simultaneous use, separate use or use spread out over time in anticancer therapy.  
   
   
       36 . Products containing a VEGF inhibitor and at least one therapeutically useful substance as defined  claim 25 , and which may contain folinic acid, in the treatment of neoplastic diseases, as a combined preparation for simultaneous use, separate use or use spread out over time in anticancer therapy.  
   
   
       37 . Products containing a VEGF inhibitor and at least one therapeutically useful substance as defined  claim 26 , and which may contain folinic acid, in the treatment of neoplastic diseases, as a combined preparation for simultaneous use, separate use or use spread out over time in anticancer therapy.  
   
   
       38 . Products containing a VEGF inhibitor and at least one therapeutically useful substance as defined  claim 27 , and which may contain folinic acid, in the treatment of neoplastic diseases, as a combined preparation for simultaneous use, separate use or use spread out over time in anticancer therapy.  
   
   
       39 . Products containing a VEGF inhibitor and at least one therapeutically useful substance as defined  claim 28 , and which may contain folinic acid, in the treatment of neoplastic diseases, as a combined preparation for simultaneous use, separate use or use spread out over time in anticancer therapy.  
   
   
       40 . Combinations containing a VEGF inhibitor with at least 5-flurorouracil or a 5-fluoropyrimidine derivative and folinic acid with the exclusion of any other chemotoxic derivative exhibiting a therapeutically synergistic effect in the treatment of neoplastic diseases.