Combination therapies for treatment of cancer

Abstract

A method for treatment of prostate cancer or benign prostate hyperplasia by combination therapy comprising administering to a patient an androgen-deprivation therapy agent and a bacteriochlorophyll derivative followed by photodynamic therapy (PDT) or vascular-targeted photodynamic therapy (VTP).

1 . A method for treatment of prostate cancer by combination therapy comprising administering to a patient in need thereof: (i) a therapeutically effective amount of an androgen-deprivation therapy (ADT) agent (hereinafter “ADT agent”); and (ii) a therapeutically effective amount of a bacteriochlorophyll derivative (Bchl-D) followed by vascular-targeted photodynamic therapy (VTP) (hereinafter “Bchl-D VTP”), wherein said ADT agent is enzalutamide that is administered once or in repeated doses, during several days, before and optionally after administration of said Bchl-D. 
     
     
         2 - 6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the Bchl-D is an anionic bacteriochlorophyll derivative optionally conjugated with an RGD-containing peptide or RGD-peptidomimetic residue. 
     
     
         8 . The method of  claim 7 , wherein the Bchl-D has the formula I: 
       
         
           
           
               
               
           
         
         wherein 
         M represents 2H or Pd; 
         R 1  is O—R 4  or —NHR 5 , wherein R 4  is selected from the group consisting of H, H + , an ammonium group or a monovalent metal cation, and R 5  is an RGD-containing peptide or RGD peptidomimetic residue; 
         R 2  is —O—C 1 -C 6  alkyl; 
         R 3  is —NH—(CH 2 ) n —SO 3   − R 6   + , wherein n is 2 or 3, and R 6   +  is a monovalent metal cation; or 
         pharmaceutically acceptable salts or optical isomers thereof. 
       
     
     
         9 . The method of  claim 8 , wherein the monovalent metal cation represented by R 4  and R 6   +  each or both are Na +  or K + , and R 2  is methoxy. 
     
     
         10 . The method of  claim 9 , wherein R 1  is O—R 4 , R 2  is methoxy, R 3  is —NH—(CH 2 ) n —SO 3   − R 6   + , wherein n is 2, and R 4  and R 6   +  are K + . 
     
     
         11 . The method of  claim 10 , wherein the Bchl-D of formula I is the compound Palladium 3 1 -oxo-15-methoxycarbonylmethyl-rhodobacteriochlorin 13 1 -(2-sulfoethyl) amide dipotassium salt (herein designated WST11) or the compound 3 1 -oxo-15-methoxycarbonylmethyl-rhodobacteriochlorin 13 1 -(2-sulfoethyl) amide dipotassium salt (herein designated STL-7012). 
     
     
         12 . The method of  claim 11 , wherein the area to be treated by said VTP is locally illuminated immediately after the administration of the Bchl-D. 
     
     
         13 . The method of  claim 11 , wherein the area to be treated by said VTP is locally illuminated at a time of up to 30 min after the administration of the Bchl-D. 
     
     
         14 . The method of  claim 9 , wherein in the Bchl-D of formula I R 1  is NH—R 5 , and R 5  is a cyclic RGD-containing peptide or a cyclic RGD-peptidomimetic residue. 
     
     
         15 . The method of  claim 14 , wherein the Bchl-D is STL-6014. 
     
     
         16 - 17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein the Bchl-D derivative is WST11. 
     
     
         19 . The method of  claim 18 , wherein the WST11 is administered once and enzalutamide is administered once before and one or several times after the administration of WST11 at determined time intervals. 
     
     
         20 - 21 . (canceled) 
     
     
         22 . The method of  claim 1 , wherein the prostate cancer is a low risk prostate cancer. 
     
     
         23 . The method of  claim 1 , wherein the prostate cancer is an intermediate risk prostate cancer. 
     
     
         24 . The method of  claim 1 , wherein the prostate cancer is a high risk prostate cancer. 
     
     
         25 . The method of  claim 1 , wherein the prostate cancer is castration-sensitive. 
     
     
         26 . The method of  claim 1 , wherein enzalutamide is administered as a single dose several days before administration of said Bchl-D, which is followed by VTP. 
     
     
         27 . The method of  claim 1 , wherein enzalutamide is administered in repeated doses, during several days, before and after administration of said Bchl-D, which is followed by VTP. 
     
     
         28 . The method of  claim 18 , wherein enzalutamide is administered daily for two weeks total both before and after VTP, starting several days before administration of WST11. 
     
     
         29 . The method of  claim 28 , wherein administration of enzalutamide starts 3 days before administration of WST11, which is followed by immediate laser local illumination of the area at 755 nm.