Phase IB study of eribulin mesylate in combination with carboplatin in patients with advanced solid tumors

2589 Background: Eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor with a novel mechanism of action, has clinical activity as monotherapy in breast cancer and other solid tumors. This phase I, open-label, dose-finding study determined the maximum tolerated dose (MTD) for eribulin in combination with carboplatin. Methods: Patients with advanced solid tumors whose prior standard therapy failed were enrolled. Carboplatin was administered by 30-min IV infusion and eribulin by 2- to 5-min IV bolus, separated by 1 h. In stage 1, eribulin mesylate (0.7, 0.9, 1.1, and 1.4 mg/m2) was dose escalated with carboplatin AUC5 in a 3+3 design in two schedules differing by the order of administration. In stage 2, eribulin mesylate (1.1 and 1.4 mg/m2) was dose escalated with carboplatin AUC6 using the preferred schedule from stage 1. In both stages, the MTD was defined as the highest dose where