title: Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Kolling Institute of Medical Research, Sydney Medical School, The University of Sydney, New South Wales 2006, Australia. b.robinson@usyd.edu.au
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Robinson
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: Annetta
authors.initials: A
authors.lastname: Krebs
authors.forename: James
authors.initials: J
authors.lastname: Vasselli
authors.forename: Robert
authors.initials: R
authors.lastname: Haddad
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002116:Calcitonin / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D018276:Carcinoma, Medullary / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D003062:Codon; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D002272:Carcinoembryonic Antigen; D003062:Codon; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D002116:Calcitonin; C452423:vandetanib