Combination Of Local And Systemic Immunomodulative Therapies For Enhanced Treatment of Cancer

Abstract

A method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic immunomodulatory anticancer agent. A further method for the treatment of cancer comprising administration of a therapeutically effective amount of an intralesional chemoablative pharmaceutical composition, or variant of said composition, in combination with a therapeutically effective amount of a systemic targeted anticancer agent. The present invention is further directed to pharmaceutical compositions for treatment of cancer. The intralesional chemoablative pharmaceutical composition can comprise an IL chemoablative agent comprising primarily a halogenated xanthene.

What is claimed as new and desired to be protected by Letters Patent is set forth in the appended claims: 
     
         1 . A method of treatment of cancer in a human comprising separately administering a therapeutically effective amount of: (1) an intralesional chemoablative pharmaceutical composition to elicit ablation of at least one cancerous tumor; and administration of (2) a therapeutically effective amount of a systemic targeted anticancer agent that is a drug that targets protein kinases and the receptors that activate them,
 wherein said intralesional chemoablative pharmaceutical composition comprises an intralesional (IL) chemoablative agent comprising rose bengal (4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein) in an appropriate pharmaceutical composition, including a 0.1% (w/v) or higher concentration aqueous solution of rose bengal, or a physiologically acceptable salt of rose bengal, said intralesional chemoablative pharmaceutical composition being administered intralesionally into said at least one cancerous tumor at about 0.1 mL/cc lesion volume to about 2 mL/cc lesion volume.   
     
     
         2 . A method of treatment of melanoma, or primary or metastatic liver cancer in a human comprising separately administering a therapeutically effective amount of: (1) an intralesional chemoablative pharmaceutical composition to elicit ablation of at least one melanoma, or primary or metastatic liver cancerous tumor; and administration of (2) a therapeutically effective amount of a systemic targeted anticancer agent,
 wherein said intralesional chemoablative pharmaceutical composition comprises an intralesional (IL) chemoablative agent comprising rose bengal (4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein) in an appropriate pharmaceutical composition, including a 0.1% (w/v) or higher concentration aqueous solution of rose bengal, or a physiologically acceptable salt of rose bengal, said intralesional chemoablative pharmaceutical composition being administered intralesionally into said at least one melanoma, or primary or metastatic liver cancerous tumor at about 0.1 mL/cc lesion volume to about 2 mL/cc lesion volume.   
     
     
         3 . A method for treatment of a cancerous tumor selected from the group consisting of melanoma, breast cancer, primary and metastatic liver cancer, prostate cancer and small cell and non small cell lung cancer in a human comprising separately administering a therapeutically effective amount of: (1) an intralesional chemoablative pharmaceutical composition to elicit ablation of at least one cancerous tumor; and (2) therapeutically effective amounts of two systemic immunomodulatory anticancer agents that are each a systemic enhancer of immune system up-regulation in a combination therapeutic regime,
 wherein said intralesional chemoablative pharmaceutical composition comprises an intralesional (IL) chemoablative agent comprising rose bengal (4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein) in an appropriate pharmaceutical composition, including a 0.1% (w/v) up to about 20% (w/v) aqueous solution of rose bengal, or a physiologically acceptable salt of rose bengal, said intralesional chemoablative pharmaceutical composition being administered intralesionally into said at least one cancerous tumor at about 0.1 mL/cc lesion volume to about 2 mL/cc lesion volume.   
     
     
         4 . The method of  claim 3 , wherein said two systemic immunomodulatory anticancer agents are each a systemic inhibitor of immune system up-regulation. 
     
     
         5 . The method of  claim 3 , wherein one of said two systemic inhibitors of immune system up-regulation is interferon-gamma.