INTEGRATED THERAPIES FOR TREATMENT OF HEMATOLOGICAL MALIGNANT DISEASES USING PIRIDOPYRIMIDININE PI3K / mTOR INHIBITORS WITH BENDAMUSTIN AND / OR RITUKSIMAB

摘要

1. A method of treating cancer in a patient, comprising administering to said patient an effective amount of (a) a compound of formula IA: or a metabolite or pharmaceutically acceptable salt thereof; and either (b) bendamustine, or (c) rituximab, or (d) a combination of bendamustine and rituximab, moreover, for a compound of formula IA: R is alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocycloalkyl, heterocycloalkylalkyl or heteroaryloarea or heteroaryl; alkyl; R is alkyl; R is hydrogen; and R is phenyl, acyl or heteroaryl, wherein said phenyl and heteroaryl are optionally substituted with 1, 2, 3, 4 or 5 R groups; and each R, if present, is independently halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, amino, alkylamino, dialkylamino, alkoxyalkyl, carboxyalkyl, alkoxycarbonyl, aminoalkyl, cycloalkyl, aryl, arylalkyl, heteroalkyl, hetero, each cycloalkyl, aryl, heterocycloalkyl and heteroaryl, individually or as part of another group within R, is independently optionally substituted with 1, 2, 3 or 4 groups selected from halogen, alkyl, haloalkyl, hydroxy, alkoxy, haloalkoxy, amino, alkylamino and dialkylamino. 2. The method of claim 1, wherein R in the compound of formula IA is alkyl, cycloalkyl, heterocycloalkylalkyl or arylalkyl; R is hydrogen or alkyl; R is alkyl; R is hydrogen; R is phenyl or heteroaryl, wherein said phenyl and heteroaryl are optionally substituted with one, two or three R groups; each R, if present, is independently amino, alkyl�