Metronomic low-dose chemotherapy as antiangiogenic therapeutic strategy for cancer.

New blood vessel formation is essential for the growth and metastasis of many cancers. As a result, antitumor activities of various angiogenesis inhibitors have been intensely explored in various tumors. Recent preclinical studies suggest that certain conventional cytotoxic agents can function as antiangiogenic drugs when administered at comparatively low doses on a continuous or very frequent schedule. Such antiangiogenic 'metronomic' scheduling of chemotherapy without extended rest periods has been shown to exert significant therapeutic antitumor efficacy with very limited toxicity in different tumor models. Combining metronomic low-dose chemotherapy regimens with specific angiogenesis inhibitors further increases efficacy. Based on the promising preclinical studies, it is anticipated that metronomic chemotherapy in combination with angiogenesis inhibitors will prove effective in clinical trials in terms of survival prolongation. While considerable progress may derive from larger randomized clinical studies, only joint efforts between basic and clinical research will ultimately advance the new paradigm of long-term metronomic antiangiogenic chemotherapy, which carries the prospect of turning cancer into a more controllable chronic disease at minimal toxicity.