Anti-angiogenic agents: clinical trial design and therapies in development.

Development of therapies aimed at inhibiting the growth of new blood vessels is among the most intensively studied approaches to the treatment of cancer. Deciphering the many biological processes involved in tumour angiogenesis has led to the development of new agents targeting either metalloproteases, angiogenic growth factors, endothelial cells or other components of the tumour neovasculature. More than 35 anti-angiogenic agents have already entered clinical trials in cancer patients and most of them are reviewed here. It has rapidly emerged from the preliminary results of these studies that the steps and endpoints classically adopted and used worldwide in developing new anticancer agents could be inappropriate to assess the efficacy of agents that do not target cancer cells directly. One of the major challenges for scientists and clinical researchers is to define new surrogate endpoints adapted to anti-angiogenic agents in the design of clinical trials. Once this has been achieved, the place of clinically active anti-angiogenic agents will need to be further refined in order to determine where they best fit in our current armamentarium, either as single agents or in combination with classical anticancer therapies. Finally, the use of these new agents may in the future encompass every aspect of cancer management, not only from palliative to curative treatment but also in the prevention of cancer.