Novel antifolate combination therapies

Abstract

A method of administering an antifolate to a mammal in need thereof, comprising administering an effective amount of said antifolate in combination with a methylmalonic acid lowering agent.

1 - 2 . (canceled)  
   
   
       3 . A method of inhibiting tumor growth in humans comprising administering to said human an effective amount of pemetrexed disodium in combination with a methylmalonic acid lowering agent selected from the group consisting of vitamin B 12,  hydroxocobalamin, cyano-10-chlorocobalamin aquocobalamin perchlorate, aquo-10-chlorocobalamin perchlorate, azidocobalamin, chlorocobalamin, cobalamin, and cyanocobalamin wherein the methylmalonic acid lowering agent is administered prior to the first administration of pemetrexed and the methylmalonic acid lowering agent administration is repeated from about every 6 weeks to about every 12 weeks.  
   
   
       4 - 33 . (canceled)  
   
   
       34 . The method of  claim 3  wherein the human is further treated with folic acid.  
   
   
       35 . The method of  claim 38  wherein about 500 μg to about 1000 μg of the methylmalonic acid lowering agent is administered.  
   
   
       36 . The method of  claim 35  wherein about 1000 μg of the methylmalonic acid lowering agent is administered.  
   
   
       37 . The method of any one of claims  3 ,  34 , or  35  wherein the methylmalonic acid lowering agent is administered by an intramuscular injection, orally, or as a parenteral.  
   
   
       38 . The method of  claim 37  wherein the methylmalonic acid lowering agent is administered by an intramuscular injection.  
   
   
       39 . The method of  claim 38  wherein the methylmalonic acid lowering agent is administered orally.  
   
   
       40 . A method of inhibiting tumor growth in humans comprising administering an effective amount of pemetrexed disodium in combination with about 500 μg to about 1500 μg of a methylmalonic acid lowering agent selected from the group consisting of vitamin B 12,  hydroxocobalamin, cyano-10-chlorocobalamin, aquocobalamin perchlorate, aquo-10-chlorocobalamin perchlorate, azidocobalamin, chlorocobalamin, cobalamin, and cyanocobalamin wherein the treatment with the methylmalonic acid lowering agent is administered by an intramuscular injection or orally and is repeated from about every 24 hours to about every 1680 hours, until treatment with pemetrexed disodium has ended.