Cephalotaxine alkaloid compositions and uses thereof

Abstract

A method of treatment of a host with a cellular proliferative disease, comprising contacting the host with a cephalotaxine and an antiproliferative agent, each in an amount sufficient to modulate said cellular proliferative disease, is described. In some embodiments, the cephalotaxine comprises homoharringtonine (cephalotaxine, 4-methyl-2-hydroxy-2-(4-hydroxy-4-methyl pentyl)butanediocate ester). Antiproliferative agents of the invention comprise alkylating agents, intercalating agents, metal coordination complexes, pyrimidine nucleosides, purine nucleosides, inhibitors of nucleic acid associated enzymes and proteins, and agents affecting structural proteins and cytoplasmic enzymes.

We claim:  
     
         1 . A method of treatment of a host with a cellular proliferative disease, comprising contacting said host with a cephalotaxine and an antiproliferative agent, each in an amount sufficient to modulate said cellular proliferative disease.  
     
     
         2 . The method according to  claim 1 , wherein said cephalotaxine comprises the butanediocate ester cephalotaxine, 4-methyl-2-hydroxy-2-(4-hydroxy-4-methyl pentyl).  
     
     
         3 . The method according to  claim 1 , wherein said cephalotaxine comprises a homoharringtonine analog.  
     
     
         4 . The method according to  claim 1  wherein said antiproliferative agent comprises an agent that interacts with nucleic acids.  
     
     
         5 . The method according to  claim 1  wherein said antiproliferative agent comprises an alkylating agent, an intercalating agent, a metal coordination complex, a pyrimidine nucleoside, a purine nucleoside, an inhibitor of nucleic acid associated enzymes, or an inhibitor of nucleic acid associated proteins.  
     
     
         6 . The method according to  claim 1  wherein said antiproliferative comprises cisplatin, cytarabine, camptothecin, vinblastine, etoposide, 5-fluorouracil, amonafide, colchicine, or genistein.  
     
     
         7 . A method according to  claim 1  wherein said cephalotaxine is administered before the administration of said antiproliferative agent.  
     
     
         8 . A method according to  claim 1  wherein said cephalotaxine is administered during the administration of said antiproliferative agent.  
     
     
         9 . A method according to  claim 1  wherein said cephalotaxine is administered after the administration of said antiproliferative agent.  
     
     
         10 . The method of  claim 1  wherein the modulation on said disease with said composition is greater than that for said antiproliferative agent alone.  
     
     
         11 . A composition comprising a cephalotaxine and an antiproliferative agent.  
     
     
         12 . The composition of  claim 11  wherein said cephalotaxine comprises homoharringtonine.  
     
     
         13 . The composition of  claim 11  wherein said antiproliferative agent comprises cisplatin, cytarabine, camptothecin, vinblastine, etoposide, 5-fluorouracil, amonafide, colchicine, or genistein.  
     
     
         14 . Use of a cephalotaxine and an antiproliferative agent in the formulation of a medicament for the treatment of a cellular proliferative disease.