Some Problems of Trial Design for Anti-Angiogenic Agents in Cancer Therapy

The propensity of tumours to generate resistant clones is a major barrier to cytotoxic and hormone therapy. The vasculature of malignancies is a more appealing target, since tumour endothelial cells are not known to be tranformed or subject to somatic mutation or random phenotypic variation. Thus an effective anti-angiogenic therapy need not be vitiated by the acquisition of resistance. Although several antiangiogenic agents have been described and used in experimental models, there remain severe problems about optimising their use and about setting up informative clinical trials. These difficulties arise predominantly because of the “invisible” nature of tumour angiogenesis.