A phase I evaluation of vandetanib plus paclitaxel, carboplatin, 5-fluorouracil, and XRT induction therapy followed by surgery for previously untreated locally advanced cancer of the esophagus and GE junction.

74 Background: Vandetanib (Vb) is an oral inhibitor that selectively targets VEGFR2, VEGFR3, RET and EGFR. Preclinical models indicate synergy with radiation and chemotherapy. We report the final results from an open-label phase I study of pre-operative Vb with carboplatin, paclitaxel, 5FU and radiation in pts with operable esophageal and GE junction (GEJ) carcinomas. Methods: Pts with operable PET/CT and EUS-staged carcinoma of the esophagus and GEJ received once daily Vb with concomitant RT (1.8 Gy/d, total 45 Gy) plus carboplatin AUC5 (d1 and 29), paclitaxel (50 mg/m2, d1,8,15,22,29), and 5-FU (CI 225 mg/m2, M-F, 5 wks). The primary objective was the safety, tolerability and the maximum tolerated dose of Vb in this combination. Planned dose escalations of Vb: 100, 200 and 300 mg daily with a “3+3” design. Results: Nine male pts (median age 58 (35-77), stage II, T2-3N0 (2 pts), III, T2-3N+ (7 pts)) were accrued between 03/2009 and 08/2010 at Fox Chase Cancer Center: 2/9 pts had esophageal squamous carci...