title: Body composition variation and impact of low skeletal muscle mass in patients with advanced medullary thyroid carcinoma treated with vandetanib: results from a placebo-controlled study.
abstract: OBJECTIVE
  Vandetanib was approved by the U.S. Food and Drug Association for the treatment of advanced medullary thyroid cancer (MTC). Because body weight (BW) loss is observed in MTC and because low skeletal muscle mass (SM) is associated with drug toxicity, this study assessed effects of vandetanib on SM and adipose tissue (AT) and explored the association between SM, toxicity, and serum concentration of vandetanib.
  
  
  METHODS
  Thirty-three patients with MTC received vandetanib (n = 23) or placebo (n = 10) in the ZETA study. Visceral AT (VAT), sc AT (SAT), and SM were assessed with computed tomography imaging by measuring tissue cross-sectional areas (square centimers per square meter). Dose-limiting toxicities (DLTs) were prospectively recorded.
  
  
  RESULTS
  Early at 3 months, compared with placebo group who lost BW, muscle, and SAT, patients treated with vandetanib gained 1.5 kg BW (P = 0.02), 1.3 cm(2)/m(2) (∼0.7 kg) of SM (P = 0.009), and 4.5 cm(2)/m(2) (∼0.5 kg) of SAT (P = 0.004) and gained more VAT, 5.1 cm(2)/m(2) (∼0.7 kg) (P = 0.02). Patients with DLT had lower SM index (37.2 vs 44.3 cm(2)/m(2), P = 0.003) and a higher vandetanib serum concentration (1091 vs 739 ng/mL, P = 0.03). Patients with SM index <43.1 cm(2)/m(2) had a higher probability of DLT (73% vs 14%, P = 0.004) and a higher vandetanib serum concentration (1037 vs 745 ng/mL, P = 0.04). Patients with the highest compared with the intermediate and lower levels of vandetanib serum concentration experienced more DLT, respectively, 78% vs 40% vs 20% (P = 0.04).
  
  
  CONCLUSIONS
  Muscle and adipose tissues are restored after only 3 months of vandetanib treatment. Patients with low muscle mass had high vandetanib serum concentration and high incidence of toxicities.
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, F-94805 Villejuif, France. marie-helene.massicotte@usherbrooke.ca
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Massicotte
authors.forename: Isabelle
authors.initials: I
authors.lastname: Borget
authors.forename: Sophie
authors.initials: S
authors.lastname: Broutin
authors.forename: Vickie E
authors.initials: VE
authors.lastname: Baracos
authors.forename: Sophie
authors.initials: S
authors.lastname: Leboulleux
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
authors.forename: Alain
authors.initials: A
authors.lastname: Deroussent
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: Sami
authors.initials: S
authors.lastname: Antoun
mesh_terms: D000328:Adult; D000368:Aged; D001823:Body Composition; D018278:Carcinoma, Neuroendocrine; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D010880:Piperidines / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C452423:vandetanib