Antivascular cancer treatments: functional assessments by dynamic contrast-enhanced magnetic resonance imaging

Abstract

New anticancer therapeutics that target tumor blood vessels promise improved efficacy and tolerability in humans. Early phase 1 drug trials have shown that the maximum tolerated dose may be inappropriate for more advanced clinical studies with efficacy endpoints. More advanced clinical trials have demonstrated that morphologic assessments of tumor response are of limited value for gauging the efficacy of treatment. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can serve as pharmacodynamic indicator of biological activity for antivascular cancer drugs by helping to define the biologically active dose. DCE-MRI studies may also predict the efficacy of treatment on the basis of changes observed. If DCE-MRI is to be used for the selection of antivascular drugs that advance into efficacy trials, then it will be necessary to develop standardized approaches to measurement and robust analytic approaches with clear accepted endpoints specified prospectively that have biological validity. Such developments will be essential for multicenter trials in which it will be necessary to establish effective cross-site standardization of measurements and evaluation.