Pharmacokinetics (PK) and pharmacodynamics (PD) of E7820-an oral sulfonamide with novel, alpha-2 integrin mediated antiangiogenic properties: Results of a phase I study

3082 Background: : E7820 is a first in class orally administered antiangiogenic sulfonamide that inhibits alpha-2 integrin. E7820 is a potent inhibitor of endothelial cell proliferation and vascular tube formation in vitro, and it effectively inhibits the growth of human breast and pancreatic cancer xenografts. Methods: This open-label, non-randomized phase I study of E7820 in patients (pts) with metastatic and/or recurrent solid tumors utilizes a standard dose escalation design to evaluate the safety and to determine the maximum tolerated dose of daily oral administration of E7820. Secondary objectives include characterization of the PK profile, assessment of PD markers (DCE-MRI, VEGF and bFGF levels in plasma and serum, and changes in alpha-2 integrin expression in circulating platelets), and preliminary exploration of antitumor activity. Results: To date, 18 pts (13 male/5 female; median age 68 [range 40–80]), have been treated with E7820 at doses ranging from 10 to 100 mg/day. No dose-limiting toxicit...