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Iodine-refractory differentiated thyroid cancer, whether locally recurrent or metastatic, is notoriously resistant to systemic chemotherapy. Differentiated thyroid cancers are characterized by upregulated expression of angiogenesis-stimulating endothelial growth factor (EGF); thus, when initial therapy fails, angiogenesis inhibition might be effective. In a phase I study, motesanib — an oral, multitargeted tyrosine kinase inhibitor of EGF receptors, platelet-derived growth-factor receptors, and KIT stem-cell–factor receptors — demonstrated activity against papillary thyroid cancer (J Clin Oncol 2007; 25:2369). Based on these results, investigators evaluated motesanib’s efficacy against iodine-refractory thyroid cancer in an industry-sponsor…