Methods for treatment of colorectal cancer using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione

Abstract

Methods of treating, preventing and/or managing cancer as well as and diseases and disorders associated with, or characterized by, undesired angiogenesis are disclosed. Specific methods encompass the administration of an immunomodulatory compound alone or in combination with a second active ingredient. The invention further relates to methods of reducing or avoiding adverse side effects associated with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy which comprise the administration of an immunomodulatory compound. Pharmaceutical compositions, single unit dosage forms, and kits suitable for use in methods of the invention are also disclosed.

1 - 21 . (canceled) 
   
   
       22 . A method of treating colorectal cancer, which comprises administering to a patient having colorectal cancer about 5 to about 50 mg per day of a compound of the formula: 
     
       
         
         
             
             
         
       
       or a pharmaceutically acceptable salt, solvate or stereoisomer thereof. 
     
   
   
       23 . The method of  claim 22 , wherein the colorectal cancer is Dukes C & D colorectal cancer, unresectable colorectal carcinoma, refractory colorectal cancer, relapsed colorectal cancer, or metastatic colorectal cancer. 
   
   
       24 . The method of  claim 22 , wherein the compound is 
     
       
         
         
             
             
         
       
     
   
   
       25 . The method of  claim 22 , wherein the compound is a pharmaceutically acceptable salt. 
   
   
       26 . The method of  claim 22 , wherein the compound is a pharmaceutically acceptable solvate. 
   
   
       27 . The method of  claim 22 , wherein the compound is a pharmaceutically acceptable stereoisomer. 
   
   
       28 . The method of  claim 27 , wherein the stereoisomer is an enantiomerically pure R isomer. 
   
   
       29 . The method of  claim 27 , wherein the stereoisomer is an enantiomerically pure S isomer. 
   
   
       30 . The method of  claim 22 , which further comprises administering a therapeutically effective amount of a second active agent. 
   
   
       31 . The method of  claim 30 , wherein the second active agent is hematopoietic growth factor, a cytokine, or an anti-cancer agent. 
   
   
       32 . The method of  claim 30 , wherein the second active agent is capecitabine, fluorouracil, leucovorin, irinotecan, xeloda, or a combination thereof. 
   
   
       33 . The method of  claim 30 , wherein the second active agent is capecitabine, xeloda, irinotecan, or a combination thereof. 
   
   
       34 . The method of  claim 30 , wherein the second active agent is capecitabine. 
   
   
       35 . The method of  claim 30 , wherein the second active agent is fluorouracil, leucovorin, irinotecan, or a combination thereof. 
   
   
       36 . The method of  claim 22 , which further comprises administering radiation therapy, hormonal therapy, biological therapy or immunotherapy. 
   
   
       37 . The method of  claim 22 , wherein the colorectal cancer is relapsed, refractory or resistant to conventional therapy. 
   
   
       38 . The method of  claim 22 , wherein the compound is administered orally. 
   
   
       39 . The method of  claim 38 , wherein the compound is administered in the form of a capsule or tablet. 
   
   
       40 . The method of  claim 22 , wherein the compound is administered in an amount of from about 10 to about 25 mg per day. 
   
   
       41 . The method of  claim 22 , wherein the compound is administered in an amount of about 5, 10, 20, 25, 30, or 50 mg per day. 
   
   
       42 . The method of  claim 22 , wherein the compound is administered in an amount of from about 5 mg per day to about 25 mg per day. 
   
   
       43 . The method of  claim 22 , wherein the compound is administered in an amount of about 25 mg per day. 
   
   
       44 . The method of  claim 22 , wherein the compound is administered cyclically. 
   
   
       45 . The method of  claim 44 , wherein one cycle comprises four to six weeks. 
   
   
       46 . The method of  claim 44 , wherein one cycle comprises the administration of the compound for 21 days followed by seven days rest. 
   
   
       47 . The method of  claim 44 , wherein the compound is administered for four to twenty-four weeks with one to six weeks of rest. 
   
   
       48 . The method of  claim 22 , wherein the compound is administered in an amount of from about 5 to about 25 mg per day for 21 days every 28 days for sixteen to twenty-four weeks. 
   
   
       49 . The method of  claim 44 , wherein the compound is administered in an amount of about 25 mg per day for 21 days followed by seven days rest in a 28 day cycle. 
   
   
       50 . The method of  claim 22 , wherein the compound is administered in an amount of about 5 mg per day. 
   
   
       51 . The method of  claim 22 , wherein the compound is administered in an amount of 10 mg per day. 
   
   
       52 . The method of  claim 22 , wherein the compound is administered in an amount of 15 mg per day. 
   
   
       53 . The method of  claim 22 , wherein the compound is administered in a capsule of 5 mg, 10 mg, 15 mg or 25 mg. 
   
   
       54 . The method of  claim 39 , wherein the capsule comprises the compound, lactose anhydrous, microcrystalline cellulose, croscarmellose sodium and magnesium stearate.