Phorbol ester compositions and methods of use for treating or reducing the duration of cytopenia

Abstract

Methods and compositions containing a phorbol ester or a derivative of a phorbol ester in combination with G-CSF or in combination with EPO, are provided for the treatment of cytopenia in mammalian subjects. The compositions and methods also reduce the duration of cytopenia such as neutropenia, thrombocytopenia, and/or anemia.

We claim: 
     
         1 . A composition comprising a phorbol ester of Formula I, pharmaceutically-acceptable salt, isomer, enantiomer, solvate, hydrate, polymorph or prodrug thereof 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are selected from the group consisting of hydrogen, hydroxyl, 
       
       
         
           
           
               
               
           
         
       
       and substituted derivatives thereof, R 3  is hydrogen, 
       
         
           
           
               
               
           
         
       
       and substituted derivatives thereof; and a granulocyte-colony stimulating factor (G-CSF). 
     
     
         2 . A composition comprising a phorbol ester of Formula I, pharmaceutically-acceptable salt, isomer, enantiomer, solvate, hydrate, polymorph or prodrug thereof 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are selected from the group consisting of hydrogen, 
       
       
         
           
           
               
               
           
         
       
       and substituted derivatives thereof, R 3  is hydrogen, 
       
         
           
           
               
               
           
         
       
       and substituted derivatives thereof; and
 an erythropoietin (EPO). 
 
     
     
         3 . The composition of  claim 1 , wherein the phorbol ester of Formula I is TPA, and TPA and G-CSF are present in an effective amount sufficient to treat or reduce the duration of cytopenia. 
     
     
         4 . The composition of  claim 3 , wherein the cytopenia is neutropenia and/or thrombocytopenia. 
     
     
         5 . The composition of  claim 2 , wherein the phorbol ester of Formula I is TPA, and TPA and EPO are present in an effective amount to treat or reduce the duration of cytopenia. 
     
     
         6 . The composition of  claim 5 , wherein the cytopenia is anemia. 
     
     
         7 . The composition of  claim 3 , wherein the effective amount is a synergistically effective amount to treat or reduce the duration of cytopenia. 
     
     
         8 . The composition of  claim 5 , wherein the effective amount is a synergistically effective amount to treat or reduce the duration of cytopenia.