A phase II trial of maintenance ADAPT therapy targeting colon cancer stem cells in patients with metastatic colorectal cancer.

TPS3650 Background: Presence of cancer stem cells (CSC) appears to be the chief cause of drug resistance to cytotoxic or targeted chemotherapy. Experimental models suggest that these resistant cancer cells undergo dormancy transition that is best targeted with a stemness modulator in its activation window through a strategy that we call ADAPT: Activating (CSC) from Dormancy And Potentiate for Targeting. In vitro and in vivo data suggest that 5FU activates while celecoxib inhibits and depletes these putative colorectal CSC. We retrospectively administer three year ADAPT therapy in unresectable metastatic colorectal cancer (MCRC) patients using capecitabine and celecoxib +/- radiation following maximal responses (complete (CR) and partial response (PR) and stable disease (SD)) to first-line combination chemotherapy. ADAPT therapy led to 30% CR and additional 10% surgical CR whose median survival reached 92.7 months in patients with unresectable MCRC. (Lin et al AACR 2010 LB-254). Methods: Fred Hutch Cancer ...