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Medline ® Abstract for Reference 30

of 'Toxicity of molecularly targeted antiangiogenic agents: Non-cardiovascular effects'

30
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Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.
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Robinson BG, Paz-Ares L, Krebs A, Vasselli J, Haddad R
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J Clin Endocrinol Metab. 2010;95(6):2664. Epub 2010 Apr 6.
 
PURPOSE: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC.
PATIENTS AND METHODS: Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors.
RESULTS: The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies.
CONCLUSIONS: Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.
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Kolling Institute of Medical Research, Sydney Medical School, The University of Sydney, New South Wales 2006, Australia. b.robinson@usyd.edu.au
PMID