Therapeutic regimen for treating cancer

Abstract

The present invention provides a method for reducing the size of a tumor in a human comprising (a) directly injecting into the tumor, via multiple injections to different points of the tumor, a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) a replication-deficient adenoviral vector comprising a nucleic acid sequence encoding TNF-α operably linked to a promoter, wherein the dose comprises about 1×10 7 to about 4×10 12 3 particle units (pu) of replication-deficient adenoviral vector, two or more times over a therapeutic period comprising up to 10 weeks, and (b) administering a dose of ionizing radiation over the duration of the therapeutic period, whereby the size of the tumor is reduced.

What is claimed is:  
     
         1 . A method for reducing the size of a tumor in a human comprising: 
 (a) directly injecting into the tumor, via multiple injections to different points of the tumor, a dose of a pharmaceutical composition comprising (i) a pharmaceutically acceptable carrier and (ii) a replication-deficient adenoviral vector comprising a nucleic acid sequence encoding TNF-α operably linked to a promoter, wherein the dose comprises about 1×10 7  to about 4×10 12  particle units (pu) of replication-deficient adenoviral vector, two or more times in a therapeutic period comprising up to about 10 weeks, and (b) administering a dose of ionizing radiation to the tumor over the duration of the therapeutic period, whereby the size of the tumor is reduced.    
     
     
         2 . The method of  claim 1 , wherein a dose of pharmaceutical composition is administered to the tumor about once a week in a therapeutic period comprising about five to ten weeks.  
     
     
         3 . The method of  claim 1 , wherein the promoter is a radiation-inducible promoter.  
     
     
         4 . The method of  claim 3 , wherein the radiation-inducible promoter is EGR- 1.  
     
     
         5 . The method of  claim 1 , wherein the dose of ionizing radiation comprises about 20 Grays (Gy) to about 70 Gy administered over the duration of the therapeutic period.  
     
     
         6 . The method of  claim 1 , wherein the multiple injections comprise 2-8 injections.  
     
     
         7 . The method of  claim 1 , wherein each injection has a penetration depth of about 1 cm to about 5 cm.  
     
     
         8 . The method of  claim 1 , wherein the method is performed before, during, or after chemotherapy or surgery.  
     
     
         9 . The method of  claim 4 , wherein the tumor is a solid tumor.  
     
     
         10 . The method of  claim 9 , wherein the tumor is associated with cancer of the breast, pancreas, colon, rectum, head/neck, or non-small cell lung carcinoma.  
     
     
         11 . The method of  claim 9 , wherein the therapeutic period comprises up to six weeks, and the method comprises administering two doses of pharmaceutical composition in weeks 1-2 and one dose of pharmaceutical composition in each subsequent week of the therapeutic period.  
     
     
         12 . The method of  claim 11 , wherein the doses of pharmaceutical composition in weeks 1-2 are administered on day 1 and day 4.  
     
     
         13 . The method of  claim 9 , wherein the multiple injections comprise 2-5 injections.  
     
     
         14 . The method of  claim 9 , wherein the dose of ionizing radiation comprises about 30 Gy to about 70 Gy of ionizing radiation.  
     
     
         15 . The method of  claim 14 , wherein the dose of ionizing radiation is administered for five consecutive days and not administered for two days in each week of weeks 1-6 of the therapeutic period.  
     
     
         16 . The method of  claim 9 , wherein the multiple injections are equally spaced around the periphery of the tumor.  
     
     
         17 . The method of  claim 9 , wherein the tumor is soft tissue sarcoma.  
     
     
         18 . The method of  claim 17 , wherein the therapeutic period comprises up to five weeks, and the method comprises administering two doses of pharmaceutical composition in week 1 and one dose of pharmaceutical composition in each subsequent week of the therapeutic period.  
     
     
         19 . The method of  claim 18 , wherein the doses of pharmaceutical composition in week 1 are administered on day 1 and day 4.  
     
     
         20 . The method of  claim 17 , wherein the multiple injections comprise 3-8 injections.  
     
     
         21 . The method of  claim 17 , wherein the dose of ionizing radiation comprises about 45 Gy to about 50 Gy of ionizing radiation.  
     
     
         22 . The method of  claim 21 , wherein the dose of ionizing radiation is administered for five consecutive days and not administered for two days in each week of weeks 1-5 of the therapeutic period.