Journal article

Clinical, Pharmacodynamic, and Pharmacokinetic Evaluation of BNC105P: A Phase I Trial of a Novel Vascular Disrupting Agent and Inhibitor of Cancer Cell Proliferation

Danny Rischin, David C Bibby, Geoff Chong, Gabriel Kremmidiotis, Annabell F Leske, Clayton A Matthews, Shirley S Wong, Mark A Rosen, Jayesh Desai

Clinical Cancer Research | AMER ASSOC CANCER RESEARCH | Published : 2011

Abstract

PURPOSE: To determine the recommended phase II dose and evaluate the safety and toxicity profile and pharmacokinetic (PK) and pharmacodynamic (PD) effects of BNC105P, an inhibitor of tubulin polymerization that has vascular disrupting and antiproliferative effects. EXPERIMENTAL DESIGN: BNC105P was administered as a 10-minute infusion on days 1 and 8 of a 21-day cycle in a first-in-human phase I study. A dynamic accelerated dose titration method was used for dose escalation. Plasma concentrations of BNC105P (phosphate prodrug) and BNC105 (active agent) were determined. PD assessments were carried out using dynamic contrast enhanced (DCE)-MRI and analysis of a blood-borne biomarker. RESULTS: T..

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