Assessment of Pharmacodynamic Vascular Response in a Phase I Trial of Combretastatin A4 Phosphate
作者： Helen L. Anderson , Jeffrey T. Yap , Mathew P. Miller , Adele Robbins , Terry Jones
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摘要: Purpose: Clinical evaluation of novel agents that target tumor blood vessels requires pharmacodynamic end points measure vascular damage. Positron emission tomography (PET) was used to the effects targeting agent combretastatin A4 phosphate (CA4P) on and normal tissue perfusion volume. Patients Methods: with advanced solid tumors were enrolled onto part a phase I, accelerated-titration, dose-escalation study. The 5 114 mg/m2 CA4P tumor, spleen, kidney investigated. Tissue measured using oxygen-15 (15O)–labeled water volume 15O-labeled carbon monoxide (C15O). Scans performed immediately before, 30 minutes 24 hours after first infusion each dose level CA4P. All statistical tests two sided. Results: PET data obtained for 13 patients intrapatient escalation. Significant dose-dependent reductions seen in afte...
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