Current status of vandetanib (ZD6474) in the treatment of non-small cell lung cancer.

Vandetanib (ZD6474) is an oral small molecule inhibitor of multiple intracellular receptor kinases, including the vascular endothelial growth factor receptor (VEGFR) -2 and epidermal growth factor receptor (EGFR). Both VEGFR and EGFR pathways have emerged as instrumental in the growth and metastasis of multiple malignancies, including non-small cell lung cancer (NSCLC). Indeed, inhibitors of each pathway have been approved by the US Food and Drug Administration for use in advanced NSCLC. As there is considerable cross talk between these pathways, dual inhibition with such agents has become an attractive strategy, with encouraging Phase II clinical trial data to date. The convenience of one oral agent targeting both pathways is clear, and clinical trials have established the maximum tolerated daily dose of vandetanib, with data from randomized Phase III trials emerging. This report will review completed and ongoing NSCLC clinical trials evaluating vandetanib, and speculate on the future of this agent in NSCLC.