Intermittent dosing of mdm2 inhibitor

Abstract

The present disclosure relates to mdm2 inhibitors for use in specific dosing schedules. It was found that if sufficiently potent or, in alternative, sufficiently high dose of a Mdm2 inhibitor is used, it can cause antineoplastic effect by triggering much longer lasting antiproliferative mechanism in cells. The long lasting effect can sustain for several weeks after a single dose, which eliminates the need for daily treatment and allows administering the Mdm2i intermittently. A treatment with the intermittent dosing schedule of a Mdm2 inhibitor can be combined with a daily treatment of the Mdm2i or with another pharmaceutically acceptable ingredient.

1 - 28 . (canceled) 
     
     
         29 . A method of treating cancer in a subject in need thereof, comprising administering a MDM2 inhibitor to the subject for at least three consecutive doses, wherein the period between each consecutive dose is at least 3 weeks and not longer than 60 days. 
     
     
         30 . The method of  claim 29 , wherein the period between each consecutive dose is 3 weeks. 
     
     
         31 . The method according to  claim 29 , wherein at least one dose of the MDM2 inhibitor is administered orally. 
     
     
         32 . The method according to  claim 29 , wherein each dose of the MDM2 inhibitor is administered orally. 
     
     
         33 . The method according to  claim 29 , wherein the cancer is amplified in MDM2. 
     
     
         34 . The method according to  claim 29 , wherein the cancer is a sarcoma. 
     
     
         35 . The method according to  claim 29 , wherein the cancer is liposarcoma. 
     
     
         36 . The method according to  claim 29 , wherein the cancer is biliary tract cancer. 
     
     
         37 . The method according to  claim 29 , wherein the subject is a human. 
     
     
         38 . The method according to  claim 29 , comprising administering another pharmaceutical ingredient to the subject. 
     
     
         39 . The method according to claim to  38 , wherein the pharmaceutical ingredient is an antineoplastic agent. 
     
     
         40 . The method according to  claim 29 , wherein each dose causes the MDM2 inhibitor to persist for at least 8 hours in plasma in vivo at least at a concentration that otherwise causes 80% tumour cell growth inhibition following exposure of the tumor cells in vitro to the MDM2 inhibitor for 8 hours, as measured by a proliferation test.