Dosage regimen for an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor

Abstract

The present invention relates to methods of treating or preventing a proliferative disease in a patient in need thereof by orally administering a therapeutically effective amount of an alpha-isoform selective phosphatidylinositol 3-kinase inhibitor compound of formula (I) or a pharmaceutically acceptable salt thereof for at least two five-consecutive day cycle, wherein said compound is not administered to the patient for a period of about two days to about three days between said five-consecutive day cycles; the use of said compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for treating or preventing a proliferative disease administered in accordance with said dosage regimen; therapeutic regimen comprising administration of said compound of formula (I) or a pharmaceutically acceptable salt thereof in accordance with said dosage regimen; and related pharmaceutical compositions and packages thereof.

What is claimed is: 
     
         1 - 13 . (canceled) 
     
     
         14 . A method of treating a cancer selected from ovary and head and neck in a patient in need thereof, comprising orally administering a therapeutically effective amount of the compound of formula (I) 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof to the patient in a daily dose of about 100 mg to about 450 mg for at least two five-consecutive day cycles, wherein said compound or a pharmaceutically acceptable salt thereof is not administered to the patient for a period of about 2 days between one five-consecutive day cycle and its subsequent five-consecutive day cycle. 
       
     
     
         15 . A method of treating ovary or head and neck cancer comprising first administering to a patient in need thereof a compound of formula (I) of  claim 14  or a pharmaceutically acceptable salt thereof in amount of about 100 mg to about 450 mg daily on a continuous daily schedule via oral administration, second determining said patient has a side effect selected from neutropenia, elevated bilirubin, cardiac toxicity, unstable angina, myocardial infarction, persistent hypertension, peripheral sensory or motor neuropathy/pain, hepatic dysfunction, reduced red and/or white blood cell count, hyperglycemia, nausea, decreased appetite, diarrhea, rash and hypersensitivity, photosensitivity, asthenia/fatigue, vomiting, stomatitis, oral mucositis, pancreatitis, dysgeusia, and dyspepsia after administration of said compound of formula (I) or a pharmaceutically acceptable salt thereof to said patient, and third reducing the administration of said compound of formula (I) or a pharmaceutically acceptable salt thereof to a daily dose of about 100 mg to about 450 mg via oral administration for at least two five-consecutive day cycles via oral administration, wherein said compound or a pharmaceutically acceptable salt thereof is not administered to the patient for a period of about 2 days between one five-consecutive day cycle and its subsequent five-consecutive day cycle. 
     
     
         16 . The method of  claim 14 , wherein the daily dose of the compound of formula (I) or a pharmaceutically acceptable salt thereof is about 200 mg to about 400 mg. 
     
     
         17 . The method of  claim 14 , wherein the compound of formula (I) or a pharmaceutically acceptable salt is orally administered once per day (q.d.) in a daily dose of about 100 mg to about 450 mg for at least two five-consecutive day cycles. 
     
     
         18 . The method of  claim 14 , wherein the compound of formula (I) or a pharmaceutically acceptable salt thereof is administered in two or more of said five-consecutive day cycles until the relief, reduction, or alleviation of the severity, occurrence rate, or frequency of at least one side effect in said patient. 
     
     
         19 . The method of  claim 18 , wherein the side effect is selected from neutropenia, elevated bilirubin, cardiac toxicity, unstable angina, myocardial infarction, persistent hypertension, peripheral sensory or motor neuropathy/pain, hepatic dysfunction, reduced red and/or white blood cell count, hyperglycemia, nausea, decreased appetite, diarrhea, rash and hypersensitivity, photosensitivity, asthenia/fatigue, vomiting, stomatitis, oral mucositis, pancreatitis, dysgeusia, and dyspepsia. 
     
     
         20 . The method of  claim 19  wherein the side effect is selected from rash and hyperglycemia. 
     
     
         21 . A method of treating ovary cancer in a patient in need thereof, comprising orally administering a therapeutically effective amount of the compound of formula (I) 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof to the patient in a daily dose of about 100 mg to about 450 mg for at least two five-consecutive day cycles, wherein said compound or a pharmaceutically acceptable salt thereof is not administered to the patient for a period of about 2 days between one five-consecutive day cycle and its subsequent five-consecutive day cycle. 
       
     
     
         22 . A method of treating head and neck cancer in a patient in need thereof, comprising orally administering a therapeutically effective amount of the compound of formula (I) 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof to the patient in a daily dose of about 100 mg to about 450 mg for at least two five-consecutive day cycles, wherein said compound or a pharmaceutically acceptable salt thereof is not administered to the patient for a period of about 2 days between one five-consecutive day cycle and its subsequent five-consecutive day cycle.