Combination comprising an atp analog and an adenosine receptor antagonist or a nucleobase/nucleoside analog for the treatment of cancer

Abstract

A method for treating an ATP analog-induced side effect in a subject comprises administering an effective amount of an adenosine receptor antagonist to the subject. A method for treating cancer in a subject comprises administering a nucleobase and/or nucleoside prior to administering an ATP analog.

1 - 233 . (canceled) 
     
     
         234 . A method for treating and/or preventing an ATP analog-induced side effect in a subject, the method comprising administering an effective amount of an adenosine receptor antagonist to the subject. 
     
     
         235 . The method of  claim 234 , wherein the ATP analog is selected from a tyrosine kinase inhibitor, an mTOR inhibitor, a Bcl-2 inhibitor, and a PARP inhibitor. 
     
     
         236 . The method of  claim 235 , wherein the PARP inhibitor comprises at least one of olaparib, ABT 888, and BSI-221. 
     
     
         237 . The method of  claim 235 , wherein the tyrosine kinase inhibitor comprises at least one of axtinib, bosutinib, brivanib, cediranib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, pazopanib, semaxanib, sorafenib, sunitinib, vandetanib, and vatalanib. 
     
     
         238 . The method of  claim 235 , wherein the Bcl-2 inhibitor comprises ABT 263. 
     
     
         239 . The method of  claim 238 , wherein the adenosine receptor antagonist is specific for the adenosine A 2B  receptor. 
     
     
         240 . The method of  claim 234 , wherein the adenosine receptor antagonist comprises at least one methylxanthine. 
     
     
         241 . The method of  claim 240 , wherein the at least one methylxanthine comprises at least one of caffeine, theophylline, and aminophylline. 
     
     
         242 . The method of  claim 234 , wherein the ATP analog and the adenosine receptor antagonist are administered simultaneously. 
     
     
         243 . The method of  claim 234 , wherein the ATP analog is administered before the adenosine receptor antagonist. 
     
     
         244 . The method of  claim 234 , wherein the adenosine receptor antagonist is administered before the ATP analog. 
     
     
         245 . The method of  claim 234 , wherein the side effect is diarrhea and/or hand-foot syndrome. 
     
     
         246 . The method of  claim 234 , further comprising maintaining or escalating dose intensity of the ATP analog. 
     
     
         247 . A method for treating and/or preventing cancer in a subject, the method comprising administering an ATP analog and an adenosine receptor antagonist to the subject. 
     
     
         248 . The method of  claim 247 , wherein the ATP analog is selected from a tyrosine kinase inhibitor, an mTOR inhibitor, a Bcl-2 inhibitor, and a PARP inhibitor. 
     
     
         249 . The method of  claim 248 , wherein the PARP inhibitor comprises at least one of olaparib, ABT 888, and BSI-221. 
     
     
         250 . The method of  claim 248 , wherein the tyrosine kinase inhibitor comprises at least one of axtinib, bosutinib, brivanib, cediranib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, pazopanib, semaxanib, sorafenib, sunitinib, vandetanib, and vatalanib. 
     
     
         251 . The method of  claim 250 , wherein the Bcl-2 inhibitor comprises ABT 263. 
     
     
         252 . The method of  claim 247 , wherein the adenosine receptor antagonist is specific for the adenosine A 2B  receptor. 
     
     
         253 . The method of  claim 247 , wherein the adenosine receptor antagonist comprises at least one methylxanthine. 
     
     
         254 . The method of  claim 253 , wherein the at least one methylxanthine comprises at least one of caffeine, theophylline, and aminophylline. 
     
     
         255 . The method of  claim 247 , wherein the ATP analog and the adenosine receptor antagonist are administered simultaneously. 
     
     
         256 . The method of  claim 247 , wherein the ATP analog is administered before the adenosine receptor antagonist. 
     
     
         257 . The method of  claim 247 , wherein the adenosine receptor antagonist is administered before the ATP analog. 
     
     
         258 . A composition comprising an ATP analog and an adenosine receptor antagonist, wherein the adenosine receptor antagonist treats and/or prevents a side effect induced by the ATP analog. 
     
     
         259 . The composition of  claim 258 , wherein the ATP analog is selected from a tyrosine kinase inhibitor, an mTOR inhibitor, a Bcl-2 inhibitor, and a PARP inhibitor. 
     
     
         260 . The composition of  claim 259 , wherein the PARP inhibitor comprises at least one of olaparib, ABT 888, and BSI-221. 
     
     
         261 . The composition of  claim 259 , wherein the tyrosine kinase inhibitor comprises at least one of axtinib, bosutinib, brivanib, cediranib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, pazopanib, semaxanib, sorafenib, sunitinib, vandetanib, and vatalanib. 
     
     
         262 . The composition of  claim 258 , wherein the adenosine receptor antagonist is specific for the adenosine A 2B  receptor. 
     
     
         263 . The composition of  claim 258 , wherein the adenosine receptor antagonist comprises at least one methylxanthine. 
     
     
         264 . The composition of  claim 263 , wherein the at least one methylxanthine comprises at least one of caffeine, theophylline, and aminophylline. 
     
     
         265 . The composition of  claim 258 , wherein the adenosine receptor antagonist reduces an ATP analog-induced side effect. 
     
     
         266 . The composition of  claim 265 , wherein the side effect is diarrhea and/or hand-foot syndrome.