Synergistic pharmaceutical combination for the treatment of squamous cell carcinoma of head and neck

Abstract

The present invention relates to a pharmaceutical combination for use in the treatment of squamous cell carcinoma, comprising a CDK inhibitor selected from the compounds of formula (I);or a pharmaceutically acceptable salt thereof and one or more antineoplastic agents selected from sorafenib, lapatinib, erlotinib, cisplatin, 5-fluorouracil, docetaxel or cetuximab or a pharmaceutically acceptable salt thereof. The said pharmaceutical combination exhibits synergy when used in the treatment of squamous cell carcinoma of head and neck (SCCHN). The invention also relates to a pharmaceutical composition comprising the said combination and a method for the treatment of squamous cell carcinoma of head and neck (SCCHN), using a therapeutically effective amount of said combination.

1 - 20 . (canceled) 
     
     
         21 . A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a CDK inhibitor of Formula I, or a pharmaceutically acceptable salt or solvate thereof, and a therapeutically effective amount of an antineoplastic agent selected from sorafenib, lapatinib, erlotinib, cisplatin, 5-fluorouracil, docetaxel, and cetuximab, wherein in Formula I Ar is 2-chloro-phenyl or 2-chloro-4-trifluoromethyl phenyl: 
       
         
           
           
               
               
           
         
       
     
     
         22 . The method of  claim 21 , wherein the pharmaceutically acceptable salt is (+)-trans-2-(2-chloro-phenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one hydrochloride. 
     
     
         23 . The method of  claim 21 , wherein the pharmaceutically acceptable salt is (+)-trans-2-(2-chloro-4-trifluoromethylphenyl)-5,7-dihydroxy-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-chromen-4-one hydrochloride. 
     
     
         24 . The method of  claim 21 , wherein the antineoplastic agent is sorafenib. 
     
     
         25 . The method of  claim 21 , wherein the antineoplastic agent is lapatinib. 
     
     
         26 . The method of  claim 21 , wherein the antineoplastic agent is erlotinib. 
     
     
         27 . The method of  claim 21 , wherein the antineoplastic agent is cisplatin. 
     
     
         28 . The method of  claim 21 , wherein the antineoplastic agent is 5-fluorouracil. 
     
     
         29 . The method of  claim 21 , wherein the antineoplastic agent is docetaxel. 
     
     
         30 . The method of  claim 21 , wherein the antineoplastic agent is cetuximab. 
     
     
         31 . The method of  claim 21 , wherein the cancer is squamous cell carcinoma. 
     
     
         32 . The method of  claim 21 , wherein the cancer is head and neck cancer. 
     
     
         33 . The method of  claim 21 , wherein the cancer is tongue cancer. 
     
     
         34 . The method of  claim 21 , wherein the cancer is pharyngeal cancer. 
     
     
         35 . The method of  claim 21 , further comprising administration of radiation.