Methods and compositions for ameliorating the undesirable effects of chemotherapy

Abstract

In one aspect, the present invention provides chemoprotectant compositions that each comprise at least two of the chemoprotectants disclosed herein. The chemoprotectant compositions of the invention are useful, for example, for ameliorating at least one adverse effect of chemotherapy. In another aspect, the present invention provides methods of ameliorating at least one adverse effect of chemotherapy, the methods each comprising the step of administering to a subject undergoing chemotherapy an amount of a chemoprotectant composition that is effective to ameliorate at least one adverse effect of the chemotherapy.

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:  
     
         1 . A chemoprotectant composition that comprises at least two chemoprotectants selected from the group consisting of methionine, N-acetyl-DL-methionine, S-adenosylmethionine, cysteine, homocysteine, cystathione, cysteamine, N-acetylcysteine, glutathione, glutathione ethylester, glutathione diethylester, glutathione triethylester, cysteamine, DiNAC, RibCys, RibCyst, β-LactCys, α-LactCys, MeliCys, MaltCys, CellCys, OTCA, allopurinol, 1-methylallopurinol, 2-methylallopurinol, 5-methylallopurinol, 7-methylallopurinol, 1,5-dimethylallopurinol, 2,5-dimethylallopurinol, 1,7-dimethylallopurinol, 2,7-dimethylallopurinol, 5,7-dimethylallopurinol, 2,5,7-trimethylallopurinol, 1-ethoxycarbonylallopurinol, 1-ethoxycarbonyl-5-methylallopurinol, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one, and 6-diSeCD.  
     
     
         2 . A chemoprotectant composition of  claim 1  comprising at least two chemoprotectants selected from the group consisting of allopurinol, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one, and N-acetylcysteine.  
     
     
         3 . A chemoprotectant composition of  claim 1  comprising allopurinol and 2-phenyl-1,2-benzoisoselenazol-3(2H)-one.  
     
     
         4 . A chemoprotectant composition of  claim 1  comprising allopurinol and N-acetylcysteine.  
     
     
         5 . A chemoprotectant composition of  claim 1  comprising 2-phenyl-1,2-benzoisoselenazol-3(2H)-one, and N-acetylcysteine.  
     
     
         6 . A method of ameliorating at least one adverse effect of chemotherapy, the method comprising the step of administering to a subject undergoing chemotherapy an amount of a chemoprotectant composition that is effective to ameliorate at least one adverse effect of the chemotherapy, said chemoprotectant composition comprising a chemoprotectant selected from the group consisting of: L-methionine, N-acetyl-DL-methionine, S-adenosylmethionine, cysteine, homocysteine, cystathione, cysteamine, N-acetylcysteine, glutathione, glutathione ethylester, glutathione diethylester, glutathione triethylester, cysteamine, DiNAC, RibCys, RibCyst, β-LactCys, α-LactCys, MeliCys, MaltCys, CeliCys, OTCA, allopurinol, 1-methylallopurinol, 2-methylallopurinol, 5-methylallopurinol, 7-methylallopurinol, 1,5-dimethylallopurinol, 2,5-dimethylallopurinol, 1,7-dimethylallopurinol, 2,7-dimethylallopurinol, 5,7-dimethylallopurinol, 2,5,7-trimethylallopurinol, 1-ethoxycarbonylallopurinol, 1-ethoxycarbonyl-5-methylallopurinol, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one, and 6-diSeCD.  
     
     
         7 . A method of  claim 6  wherein said chemoprotectant composition comprises a chemoprotectant selected from the group consisting of allopurinol, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one, and N-acetylcysteine.  
     
     
         8 . A method of  claim 6  wherein said chemoprotectant composition comprises allopurinol and 2-phenyl-1,2-benzoisoselenazol-3(2H)-one.  
     
     
         9 . A method of  claim 8  wherein said allopurinol is administered in an amount of from 10 to 2400 mg/day, and said 2-phenyl-1,2-benzoisoselenazol-3(2H)-one is administered in an amount of from 5 to 5000 mg/day.  
     
     
         10 . A method of  claim 6  wherein said chemoprotectant composition comprises allopurinol and N-acetylcysteine.  
     
     
         11 . A method of  claim 10  wherein said allopurinol is administered in an amount of from 10 to 2400 mg/day, and said N-acetylcysteine is administered in an amount of from 5 to 5000 mg/day.  
     
     
         12 . A method of  claim 6  wherein said chemoprotectant composition comprises 2-phenyl-1,2-benzoisoselenazol-3(2H)-one, and N-acetylcysteine.  
     
     
         13 . A method of  claim 12  wherein said 2-phenyl-1,2-benzoisoselenazol-3(2H)-one is administered in an amount of from 5-5000 mg/day, and said N-acetylcysteine is administered in an amount of from 5 to 5000 mg/day.  
     
     
         14 . A chemoprotectant composition comprising: 
 (a) a chemoprotectant selected from the group consisting of methionine, N-acetyl-DL-methionine, S-adenosylmethionine, cysteine, N-acetylcysteine, glutathione, glutathione ethylester, glutathione diethylester, glutathione triethylester, DiNAC, RibCys, homocysteine, cystathione, cysteamine, OTCA and RibCyst;    (b) a chemoprotectant selected from the group consisting of allopurinol, 1-methylallopurinol, 2-methylallopurinol, 5-methylallopurinol, 7-methylallopurinol, 1,5-dimethylallopurinol, 2,5-dimethylallopurinol, 1,7-dimethylallopurinol, 2,7-dimethylallopurinol, 5,7-dimethylallopurinol, 2,5,7-trimethylallopurinol, 1-ethoxycarbonylallopurinol, and 1-ethoxycarbonyl-5-methylallopurinol; and    (c) a chemoprotectant selected from the group consisting of Ebselen and 6-diSeCD.    
     
     
         15 . A pharmaceutical composition comprising: 
 (a) a chemoprotectant selected from the group consisting of methionine, N-acetyl-DL-methionine, S-adenosylmethionine, cysteine, homocysteine, cystathione, cysteamine, N-acetylcysteine, glutathione, glutathione ethylester, glutathione diethylester, glutathione triethylester, cysteamine, DiNAC, RibCys, RibCyst, β-LactCys, α-LactCys, MeliCys, MaltCys, CellCys, OTCA, allopurinol, 1-methylallopurinol, 2-methylallopurinol, 5-methylallopurinol, 7-methylallopurinol, 1,5-dimethylallopurinol, 2,5-dimethylallopurinol, 1,7-dimethylallopurinol, 2,7-dimethylallopurinol, 5,7-dimethylallopurinol, 2,5,7-trimethylallopurinol, 1-ethoxycarbonylallopurinol, 1-ethoxycarbonyl-5-methylallopurinol, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one, and 6-diSeCD; and    (b) a chemotherapeutic agent.    
     
     
         16 . A method of  claim 15  wherein said chemotherapeutic agent comprises platinum.  
     
     
         17 . A method of  claim 16  wherein said chemotherapeutic agent comprises cisplatin.