Assessment of metabolism, excretion and pharmacokinetics of a single dose of [14C]-ZD6126 in patients with solid malignant tumors

3083 Background: ZD6126 is a novel vascular-targeting agent that causes disruption of the microtubular network responsible for maintaining the shape of immature, proliferating endothelial cells in tumor vasculature. This leads to selective vessel occlusion and extensive tumor necrosis. Methods: A Phase I excretion balance study of ZD6126 has been conducted in 6 patients (47–56 yrs) with solid tumors refractory to standard therapies, a WHO performance status of 0–2 and a life expectancy of ≥12 weeks. Those with significant cardiac, hematopoietic, hepatic or renal dysfunction were excluded. Patients received a single 10 min infusion of 40 mg/m2 [14C]-ZD6126 (70 μCi; 2.6 MBq) on day 1 of a 28-day cycle. Urine and feces were collected continuously for the first 8 days and blood samples were collected on days 1 and 2. Subsequent treatment comprised a single i.v. infusion of ZD6126 (56 mg/m2). Results: Pharmacokinetic analysis showed that Cmax for plasma ZD6126 was observed 5 min into the 10 min infusion. Conce...