A New Spectrum of Skin Toxic Effects Associated With the Multikinase Inhibitor Vandetanib

Abstract

S kin manifestations are among the most frequent adverse effects of targeted therapies. 1Hyperkeratosis and hand-foot skin reaction are observed with most raf and vascular endothelial growth factor (VEGF) inhibitors, whereas folliculitis is a hallmark of epidermal growth factor receptor (EGFR) blocking agents. 1 Vandetanib (Zactima, ZD6474; AstraZeneca) is a multikinase inhibitor that targets EGFR, VEGF receptors 1, 2, and 3 and the RET (rearranged during transfection) receptor. 2Methods.Between November 2005 and October 2009, patients with metastatic thyroid cancer received vandetanib at a dose of 300 mg/d in 3 clinical trials: a phase 2 open-label study (NCT00098345) 3 and 2 randomized phase 3 studies comparing vandetanib with a placebo (NCT00537095 and NCT00410761).Clinical examination of all patients exhibiting any skin manifestation was performed.Skin toxic effects were assessed using version 3 of the National Cancer Institute Common Terminology Criteria (http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm), and additional drug intake was recorded.All patients participating in this study provided a written informed consent for the clinical trials.