Combination cancer therapy with bis(thiohydrazide) amide compounds

Abstract

Disclosed is a method of treating a subject with cancer, the method comprising the step of co-administering to the subject over three to five weeks, a taxane in an amount of between about 243 μmol/m 2 to 315 μmol/m 2 ; and a bis(thiohydrazide amide) compound in an amount between about 1473 μmol/m 2 and about 1722 μmol/m 2 .

1 . A method of treating a human with ovarian cancer comprising the step of co-administering to the human over three to five weeks: paclitaxel or a paclitaxel analogue in an amount of between about 243 μmol/m 2  to 315 μmol/m 2 ; and a bis(thiohydrazide amide) in an amount between about 1473 μmol/m 2  and about 1722 μmol/m 2 , wherein the bis(thiohydrazide amide) is represented by the following Structural Formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the bis(thiohydrazide amide) is administered in combination with paclitaxel or docetaxel. 
     
     
         3 . The method of  claim 2 , wherein the bis(thiohydrazide amide) is administered in combination with paclitaxel. 
     
     
         4 . The method of  claim 3 , wherein the paclitaxel and the bis(thiohydrazide amide) are each administered in three equal weekly doses of three weeks of a four week period. 
     
     
         5 . The method of  claim 4 , further comprising repeating the four week administration period until the cancer is in remission. 
     
     
         6 . The method of  claim 5 , wherein the paclitaxel is intravenously administered in a weekly dose of about 94 μmol/m 2 . 
     
     
         7 . The method of  claim 6 , wherein the bis(thiohydrazide amide) is intravenously administered in a weekly dose of between about 500 μmol/m 2  and about 562 μmol/m 2 . 
     
     
         8 . The method of  claim 7 , wherein the bis(thiohydrazide amide) is intravenously administered in a weekly dose of 532 μmol/m 2 . 
     
     
         9 . The method of  claim 1 , wherein the bis(thiohydrazide amide) is the disodium or dipotassium salt. 
     
     
         10 . A method of treating a human with cancer, comprising intravenously administering to the human in a four week period, three equal weekly doses of the paclitaxel in an amount of about 94 μmol/m 2  and a bis(thiohydrazide amide) represented by the following Structural Formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof in an amout of about 532 μmol/m 2 , wherein the cancer is ovarian cancer.