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Anti-cancer potential of tumor-vascular disrupting agents: review of the latest clinical evidence

Bruce C Baguley

Solid tumors differ from normal tissue by having a low vascular density, leading to various forms of vascular stress. Tumor vascular disrupting agents (VDAs) act to potentiate this stress, increasing vascular permeability and decreasing blood flow. Two main classes of tumor VDAs have progressed so far to clinical trial: the ‘flavonoid’ class, represented by vadimezan, and the tubulin poisons, represented by fosbretabulin (combretastatin A-4 phosphate). Both classes have been tested clinically, generally in combination with cytotoxic drugs such as carboplatin and paclitaxel. An important feature of trials is the measurement of effects on tumor vascular permeability and blood flow. Dynamic contrast-enhanced MRI, using a gadolinium-based biomarker, has been commonly employed. Promising clinical results, as well as indications of efficacy as tumor VDAs, have been obtained in Phase II clinical trials. However, Phase III trials have not yet demonstrated an increase in patient survival.