Pharmacokinetic and pharmacodynamic analysis of gastric cancer patients treated with telatinib.

113 Background: The soluble form of the VEGFR2 receptor (sVEGFR2) neutralizes circulating VEGF, and functions as a negative feedback mechanism to enable partial inhibition of VEGF-stimulated endothelial cell migration and proliferation. In response to inhibition of VEGFR2 tyrosine kinase activity, up-regulation of VEGF expression and down-regulation of sVEGFR2 expression levels have been observed (Murukesh et al., 2010). Telatinib (tel) is a novel orally available kinase inhibitor that is highly selective for the VEGFR, PDGFR, and KIT tyrosine kinases at nanomolar concentrations with potent antiangiogenic activity. Correlation between telatinib exposure and reduction in plasma sVEGFR2 levels from baseline has previously been demonstrated in patient serum samples in phase I studies. Methods: TEL0805, a phase II study administered tel with capecitabine (X) and cisplatin (P) in previously untreated metastatic or unresectable gastric or GEJ adenocarcinoma pts. Patient serum samples were obtained on day -7, [6...