Challenges of antiangiogenic therapy of tumors

Abstract

After the approval of the first antiangiogenic agent, bevacizumab, in February 2004, a humanized monoclonal antibody anti-vascular endothelial growth factor (VEGF), this category of new anticancer drugs expanded rapidly. At the end of 2006, the U.S. Food and Drug Administration (FDA) approved bevacizumab for therapy of advanced colorectal and non-small cell lung cancers (except squamous cell histotype), sunitinib for advancedrefractory renal cancer and for imatinib-resistant gastro-intestinal stromal tumors (GISTs), and sorafenib for recurrent advanced kidney cancer. Twelve antiangiogenic drugs entered Phase III trials and at least another 15-20 are under evaluation in Phase I-II studies. Such a rapid clinical development of inhibitors of angiogenesis with different pharmacodynamic and pharmacokinetic characteristics opens a number of challenges, including: the identification of targets of choice; the optimal therapeutic strategy; the rational selection of the patients; proper study-design of clinical trials as well as the monitoring of drug efficacy; management of toxicity; and, finally, the determination of the disease stage to obtain the best benefit. All the above relevant issues are presented and discussed in this chapter. © 2008 Springer US.