A phase I study of the novel, third generation epothilone ZK-EPO in patients with advanced solid tumors

2051 Background: Epothilones are a new class of cytotoxic agents that induce tubulin polymerization. ZK-EPO, the only fully synthetic, third-generation analogue of epothilone B, is a highly potent tubulin stabilizer that has shown substantial preclinical antitumor activity, including against taxane-resistant models. This Phase I study was initiated to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of ZK-EPO in patients with advanced solid tumors. Secondary objectives were to determine the safety, tolerability, pharmacokinetics and antitumor activity of ZK-EPO. Methods: Patients with histologically confirmed advanced solid tumors that were resistant/refractory to conventional antineoplastic treatment (n=44), or for whom no standard therapy was available (n=3), were enrolled on the trial. ZK-EPO was given as a 30-minute intravenous infusion once every 3 weeks; the starting dose was 0.6 mg/m2, and dose levels were escalated using a modified Fibonacci design. Treatment was conti...