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Research Letter
Dec 2012

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

Author Affiliations

Author Affiliations: Departments of Dermatology (Drs Giacchero, Arnault, Maksimovic, Mateus, and Robert), Pathology (Drs Tomasic and Wechsler), Endocrinology, and Nuclear Medicine (Dr Schlumberger), Gustave Roussy Institute, Villejuif, France; and Departments of Endocrinology and Nuclear Medicine, University of Paris-Sud, Villejuif (Dr Schlumberger).

Arch Dermatol. 2012;148(12):1418-1420. doi:10.1001/2013.jamadermatol.192

Skin manifestations are among the most frequent adverse effects of targeted therapies.1 Hyperkeratosis 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.2

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. This study was conducted according to the Declaration of Helsinki Good Clinical Practice guidelines and in accordance with applicable local laws and regulations.