Dynamic Contrast-Enhanced Magnetic Resonance Imaging As a Pharmacodynamic Measure of Response After Acute Dosing of AG-013736, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors: Results From a Phase I Study

Purpose Identifying suitable markers of biologic activity is important when assessing novel compounds such as angiogenesis inhibitors to optimize the dose and schedule of therapy. Here we present the pharmacodynamic response to acute dosing of AG-013736 measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Patients and Methods Thirty-six patients with advanced solid tumors were treated with various doses of AG-013736. In addition to standard measures of objective disease response and pharmacokinetic analysis, DCE-MRI scans were acquired at baseline and repeated at cycle 1—day 2 after the scheduled morning dose of the AG-013736 in 26 patients. Indicators of a vascular response, such as the volume transfer constant (Ktrans) and initial area under the curve (IAUC), were calculated to assess the effect of treatment on tumor vascular function. Results Evaluable vascular response data were obtained in 17 (65%) of 26 patients. A linear correlation was found in which the percentage change fr...