Vandetanib (100 mg) in Patients with Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer

• Published in: The journal of clinical endocrinology and metabolism 2010-06, Vol.95 (6), p.2664-2671
• Main Authors: Robinson, Bruce G., Paz-Ares, Luis, Krebs, Annetta, Vasselli, James, Haddad, Robert
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Calcitonin - blood; Carcinoembryonic Antigen - blood; Carcinoma, Medullary - drug therapy; Carcinoma, Medullary - genetics; Carcinoma, Medullary - pathology; Codon; Double-Blind Method; Endocrinopathies; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Humans; Magnetic Resonance Imaging; Male; Malignant tumors; Medical sciences; Middle Aged; Neoplasm Metastasis; Original; Piperidines - adverse effects; Piperidines - therapeutic use; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Quinazolines - adverse effects; Quinazolines - therapeutic use; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; Thyroid. Thyroid axis (diseases); Tomography, X-Ray Computed; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2009-2461

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. Vandetanib at 100 mg/day has clinically relevant antitumor activity and an acceptable safety profile in patients with advanced or metastatic hereditary medullary thyroid cancer.