Dynamic Contrast-Enhanced Magnetic Resonance Imaging As a Biomarker for the Pharmacological Response of PTK787/ZK 222584, an Inhibitor of the Vascular Endothelial Growth Factor Receptor Tyrosine Kinases, in Patients With Advanced Colorectal Cancer and Liver Metastases: Results From Two Phase I Studies
作者： Bruno Morgan , Anne L Thomas , Joachim Drevs , Juergen Hennig , Martin Buchert
关键词: Internal medicine 、 Angiogenesis inhibitor 、 Vascular endothelial growth factor 、 Angiogenesis 、 Metastasis 、 Tyrosine kinase 、 Cancer research 、 Receptor tyrosine kinase 、 Growth factor receptor 、 Vatalanib 、 Medicine 、 Endocrinology
摘要: Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) patients with advanced colorectal cancer treated two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six had DCE-MRI performed at baseline, day 2, the end each 28-day cycle. Doses oral ranged from 50 to 2000 mg once daily. Tumor permeability vascularity assessed calculating bidirectional transfer constant (Ki). percentage baseline Ki (% Ki) time point was compared pharmacokinetic clinical points. Results: A significant negative correlation exists between % increase dose plasma leve...
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