A phase I study of dovitinib in combination with capecitabine and oxaliplatin in upfront treatment of advanced colorectal and gastric cancer with a dose expansion cohort in advanced gastric cancer.

TPS174 Background: Dovitinib (TKI258) is an investigational multi-targeting tyrosine kinase inhibitor with potent inhibitory activity against several class III,IV,V RTKs relevant in cancer, including VEGF receptors-1,2,3, bFGF receptors-1,2,3, PDGFR and c-KIT. The addition of bevacizumab to chemotherapy is presently employed in management of colorectal cancer but did not improve survival in gastric cancer (AVAGAST). FGF pathway activation has been related to aggressive gastric and colorectal cancer, resistance to anti-VEGF therapy may be mediated in part by FGF upregulation. FGFR2 amplification is reported in subsets of gastric cancer (Hara et al. Lab Invest (1998) 78(9):1143-53). FGFR2 is required for cell proliferation and survival in FGFR2 amplified gastric cancer cell lines (Kunli et al. Cancer Rsch (2008) 68; 2340), which are sensitive to FGFR2 inhibitors, including Dovitinib. Methods: This trial is a single arm open label phase I trial in patients with treatment naive advanced gastric or colorectal ...