ABSTRACT
Introduction ................................................................................................ 181 Enhancement of chemotherapy efficacy by antiangiogenic drug-induced vessel normalization, transiently decreased hypoxia, reduced interstitial fluid pressures, and enhanced intratumoral chemotherapy drug delivery ................................................................... 182 Enhancement of chemotherapy efficacy by antiangiogenic drug facilitation of chemotherapy targeting of dividing endothelial cells in growing tumor vasculature................................... 184 Enhancement of chemotherapy efficacy by antiangiogenic drugs by suppression of circulating proangiogenic bone marrow-derived cells including endothelial progenitor cells .. 185 Antiangiogenic therapies as a means of slowing down tumor cell reproduction after MTD cytotoxic chemotherapy............ 188 Summary and conclusions ....................................................................... 190 Acknowledgments ..................................................................................... 193 References .................................................................................................. 193
Introduction The design of the pivotal randomized phase III clinical trial that led to the subsequent approval of the first antiangiogenic drug for the treatment of cancer, bevacizumab (Avastin®), is also notable for highlighting a fundamental
paradox in the antiangiogenic therapy research field: why would a tumor starving drug such as bevacizumab that eliminates some tumor blood vessels or prevents new ones from forming and suppresses tumor blood flow as well as perfusion of other vessels increase the efficacy of combined chemotherapy (rather than the opposite) as first shown by Teicher and colleagues?1
