The combination of antiangiogenic therapy with other modalities.

A B S T R A C T Angiogenesis is critical for a number of physiologic and pathophysiologic processes, and several angiogenesis inhibitors are now in clinical trials for the treatment of cancer. Antiangiogenic therapy offers a number of potential benefits including lack of drug resistance for some agents, synergistic interaction with other modalities, lack of significant toxicity compared with conventional agents, and a potent antitumor effect. However, no angiogenesis inhibitor has been approved for clinical use. Although antiangiogenic agents offer great therapeutic potential, preclinical and early clinical trial results suggest that these agents will have a delayed onset of activity and may induce stabilization of disease, and not regression, in patients with advanced disease. Studies suggest that regulation of angiogenesis in various capillary beds may be differentially regulated, suggesting that antiangiogenic therapy may require organ-specific optimization. By combining antiangiogenic agents with each other and/or with other modalities used in the treatment of cancer, the limitations of each therapeutic approach will be overcome, leading to enhanced efficacy with diminished toxicity. However, the optimal strategies for the use, monitoring, and validation of antiangiogenic agents in the clinic remains unclear. Before these agents can be integrated into clinical practice, a better understanding of their mechanism of action and regulation is required.