Treatment of cancer with specific rxr agonists

Abstract

A method of treating cancer is disclosed comprising administering to a patient in need of such treatment a RXR agonist at a level below the RAR activating threshold and at or above the RXR effective dose.

What is claimed is: 
     
         1 . A method of treating cancer, wherein the cancer is a sarcoma, comprising administering to a patient in need of such treatment a retinoid X receptor (RXR) agonist at a dose below the Retinoic Acid Receptor (RAR) activating threshold and at or above the RXR effective dose, wherein the RXR agonist has the chemical structure 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof; where R is H or lower alkyl of 1 to 6 carbons, and the dose of the RXR agonist is from about 0.1 to about 20 mg/m 2 /day. 
       
     
     
         2 . The method according to  claim 1 , wherein the RAR activating threshold and the RXR effective dose for the patient is determined by dosing the patient with increasing concentrations of a RXR agonist to until the RXR effective dose and the RAR activating threshold are reached. 
     
     
         3 . The method according to  claim 2 , wherein the RXR effective dose is determined by measuring the reduction of the patient's TSH levels or at least one RAR biomarker expressed by the patient. 
     
     
         4 . The method according to  claim 3 , wherein the RAR biomarker is selected from the group consisting of CYP26 level, CRBPI level, and combinations thereof. 
     
     
         5 . The method according to  claim 1 , further comprising the steps of measuring the patient's C max  of the RXR agonist, and adjusting the dose to maintain the patient's C max  at an optimal level. 
     
     
         6 . The method according to  claim 1 , further comprising treating the patient with an anti-cancer agent. 
     
     
         7 . The method according to  claim 6 , wherein the anti-cancer agent is selected from the group consisting of a platinum-based compound, cytotoxic drug and mixtures thereof. 
     
     
         8 . The method according to  claim 6 , wherein the anti-cancer agent is a monoclonal antibody. 
     
     
         9 . The method according to  claim 1 , further comprising treating the patient with a TSH modulating agent 
     
     
         10 . The method according to  claim 9 , wherein the TSH modulating agent is a thyroid hormone. 
     
     
         11 . The method according to  claim 1 , further comprising treating the patient with a triglyceride lowering agent. 
     
     
         12 . The method according to  claim 1 , wherein the dose of the RXR agonist is from about 1 to about 20 mg/m 2 /day. 
     
     
         13 . The method according to  claim 1 , wherein the dose of the RXR agonist is from about 0.1 to about 10 mg/m 2 /day. 
     
     
         14 . The method according to  claim 1 , wherein the dose of the RXR agonist is from about 0.5 to about 2 mg/m 2 /day. 
     
     
         15 . The method according to  claim 1 , wherein the RXR agonist is 3,7-dimethyl-6(S),7(S)-methano,7-[1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphth-7-yl]2(E),4(E) heptadienoic acid. 
     
     
         16 . The method according to  claim 1 , wherein R is lower alkyl or 1 to 6 carbons. 
     
     
         17 . The method according to  claim 1 , comprising administering the pharmaceutically acceptable salt. 
     
     
         18 . The method according to  claim 1 , wherein the patient is a human. 
     
     
         19 . The method according to  claim 1 , wherein the cancer is Osteosarcoma/Malignant Fibrous Histiocytoma of bone, Clear Cell Sarcoma of Tendon Sheaths, Kaposi's Sarcoma, Rhabdomyosarcoma, Ewing's Family of Tumors sarcoma, Childhood Soft Tissue Sarcoma, Adult Soft Tissue Sarcoma, Uterine Sarcoma. 
     
     
         20 . The method according to  claim 1 , wherein the cancer is Soft Tissue Sarcoma.