Anticancer therapy

Abstract

A subject afflicted with a cancer or precancerous condition is treated by administering an agent that increases expression of somatostatin receptors, and a cytotoxic recognition ligand. In an alternative embodiment, somatostatin analogs, which are radiolabeled are used to treat cancer or precancerous conditions.

1 . A radiopharmaceutical composition comprising: 
 a therapeutic agent comprising  213 Bi; and    a pharmaceutically acceptable carrier.    
     
     
         2 . The radiopharmaceutical composition of  claim 1  wherein the therapeutic agent further comprises a targeting moiety that targets the therapeutic agent to a selected mammalian cell.  
     
     
         3 . The radiopharmaceutical composition of  claim 2  wherein the targeting moiety binds to a component of the mammalian cell membrane.  
     
     
         4 . The radiopharmaceutical composition of  claim 2  wherein the targeting moiety facilitates internalization of the therapeutic agent by the cell.  
     
     
         5 . The radiopharmaceutical composition of  claim 2  wherein the selected mammalian cell is a cancer cell.  
     
     
         6 . The radiopharmaceutical composition of  claim 2  wherein the selected mammalian cell is a tumor cell.  
     
     
         7 . The radiopharmaceutical composition of  claim 6  wherein the tumor cell is a cancer cell.  
     
     
         8 . The radiopharmaceutical composition of  claim 1  wherein the therapeutic agent comprises a peptide, a peptide analog, a peptide derivative or a peptidomimetic compound.  
     
     
         9 . The radiopharmaceutical composition of  claim 1  wherein the therapeutic agent is effective in peptide receptor radionuclide therapy (PRRT).  
     
     
         10 . The radiopharmaceutical composition of  claim 8  wherein the therapeutic agent binds a mammalian peptide receptor.  
     
     
         11 . The radiopharmaceutical composition of  claim 10  wherein the peptide receptor is a component of a tumor cell.  
     
     
         12 . A radiopharmaceutical composition comprising: 
 a somatostatin peptide or analog or derivative thereof, comprising  213 Bi; and    a pharmaceutically acceptable carrier.    
     
     
         13 . A radiopharmaceutical composition comprising: 
 an octreotide or analog or derivative thereof, comprising  213 Bi; and    a pharmaceutically acceptable carrier.    
     
     
         14 . A radiopharmaceutical composition comprising: 
   213 Bi-DOTATOC; and    a pharmaceutically acceptable carrier.    
     
     
         15 . A radiopharmaceutical composition comprising: 
 a therapeutic agent comprising a high linear energy transfer α-emitter radionuclide; and    a pharmaceutically acceptable carrier.    
     
     
         16 . The radiopharmaceutical composition of  claim 15  wherein the therapeutic agent further comprises a targeting moiety that targets the therapeutic agent to a selected mammalian tumor cell.  
     
     
         17 . The radiopharmaceutical composition of  claim 15  wherein the therapeutic agent comprises a somatostatin or analog or derivative thereof.  
     
     
         18 . A method for treating disease in a mammalian patient comprising administering to a mammalian patient in need thereof the radiopharmaceutical composition of  claim 1 .  
     
     
         19 . The method of  claim 18  wherein the disease is cancer.  
     
     
         20 . The method of  claim 18  wherein the therapeutic agent is targeted to a tumor.  
     
     
         21 . The method of  claim 20  wherein the tumor is a pancreatic tumor.  
     
     
         22 . The method of  claim 18  wherein the radiopharmaceutical composition is administered systemically.  
     
     
         23 . The method of  claim 18  wherein the radiopharmaceutical composition is administered in a plurality of doses over a period of time.  
     
     
         24 . A method for treating disease in a mammalian patient, said patient suffering from a disease treatable with a therapeutic agent comprising  90 Y, the method comprising administering to the patient a radiopharmaceutical composition comprising an analogous therapeutic agent comprising  213 Bi in place of  90 Y.  
     
     
         25 . A method of treating a subject afflicted with a cancer or precancerous condition, comprising: 
 administering a first therapeutic agent to the subject, wherein the first therapeutic agent increases the expression level of somatostatin receptors in a cancer cell; and    administering a second therapeutic agent to the subject, wherein the second therapeutic agent comprises: 
 a recognition ligand that selectively binds to a somatostatin receptor on the cancer cell; and  
 a cytotoxic compound;  
 so as to cause a deleterious effect on cancer cell.  
   
     
     
         26 . The method of  claim 25 , wherein the cancer is in the form of a tumor.  
     
     
         27 . The method of  claim 25 , wherein the cancer comprises a carcinoma, a sarcoma, or a lymphoma.  
     
     
         28 . The method of  claim 25 , wherein the cancer is selected from the group consisting of breast, pancreatic, gastric, prostate, renal, colorectal, thyroid, lung, kidney, liver, central nervous system, and malignant lymphoid cancer.  
     
     
         29 . The method of  claim 25 , wherein the cancer comprises a cancer of the neuroendocrine or central nervous system.  
     
     
         30 . The method of  claim 25 , wherein the first therapeutic agent comprises a nucleoside analog.  
     
     
         31 . The method of  claim 30 , wherein the nucleoside analog comprises a 2,2-difluoro-2-deoxyribose group.  
     
     
         32 . The method of  claim 30 , nucleoside analog comprises a deoxycytidine derivative.  
     
     
         33 . The method of  claim 32 , wherein the deoxycytidine derivative comprises gemcitabine or an active gemcitabine metabolite.  
     
     
         34 . The method of  claim 30 , wherein the first therapeutic agent or an active metabolite thereof comprises a ribonucleotide reductase inhibitor.  
     
     
         35 . The method of  claim 25 , wherein the cytotoxic compound comprises a radionuclide.  
     
     
         36 . The method of  claim 35 , wherein the radionuclide is selected from the group consisting of  90 yttrium,  111 indium,  177 lutetium,  225 actinium,  209 bismuth,  212 bismuth,  213 bismuth,  64 copper,  67 copper,  76 arsenic,  77 arsenic,  203 lead,  209 lead,  212 lead,  166 holmium,  153 promethium,  186 rhenium,  188 rhenium, and  211 astatine.  
     
     
         37 . The method of  claim 35 , wherein the recognition ligand comprises a somatostatin analog.  
     
     
         38 . The method of  claim 35 , wherein the recognition ligand comprises octreotide, lanreotide or vapreotide.  
     
     
         39 . The method of  claim 25 , wherein the second therapeutic agent is administered after the first therapeutic agent is administered.  
     
     
         40 . The method of  claim 39 , wherein the second therapeutic agent is administered at least 24 hours after the first therapeutic agent is administered.  
     
     
         41 . The method of  claim 40 , wherein the second therapeutic agent is administered at least 96 hours after the first therapeutic agent is administered.  
     
     
         42 . The method of  claim 25 , wherein treatment of the cancer by administration of the first therapeutic agent and the second therapeutic agent is synergistic.  
     
     
         43 . The method of  claim 25 , wherein the subject is a human.  
     
     
         44 . A method of treating a subject with a cancer or precancerous condition, comprising: 
 administering a first therapeutic agent to the subject, wherein the first therapeutic agent comprises a nucleoside analog; and    administering a second therapeutic agent to the subject, wherein the second therapeutic agent comprises a somatostatin analog and a cytotoxic compound;    so as to cause a deleterious effect on cancer cells of the subject.    
     
     
         45 . The method of  claim 44 , wherein the nucleoside analog comprises gemcitabine, 2′,2′-difluoro-2′-deoxycytidine diphosphate, or 2′,2′-difluoro-2′-deoxycytidine triphosphate.  
     
     
         46 . The method of  claim 44 , wherein the cytotoxic compound comprises a radionuclide.  
     
     
         47 . The method of  claim 46 , wherein the somatostatin analog is selected from the group consisting of octreotide, lanreotide, depreotide, and vapreotide, and derivatives thereof; and wherein the radionucleotide selected from the group consisting of  90 yttrium,  111 indium,  177 lutetium,  225 actinium,  209 bismuth,  212 bismuth  213 bismuth,  64 copper,  67 copper,  76 arsenic,  77 arsenic,  203 lead,  209 lead,  212 lead,  166 holmium,  153 promethium,  186 rhenium,  188 rhenium, and  211 astatine.