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While continued VEGF inhibition is thought to maintain important anti-angiogenic effects that keep tumor cells from growing and spreading, cessation of VEGF suppression may diminish those effects. In fact, in preclinical models, withdrawal of an anti-VEGF agent has been shown to result in regrowth of tumor vasculature.15-18 This vessel regrowth may be particularly rapid along the basement membrane tracks left by previously regressed vasculature.17,18 These proposed effects influence clinical trial design. Specifically, many clinical trials with anti-VEGF agents have been designed to maintain VEGF inhibition, even in instances in which administration of accompanying antitumor compounds may be modified.19-22
