Details

Autor(en) / Beteiligte

• Massicotte, Marie-Hélène
• Borget, Isabelle
• Broutin, Sophie
• Baracos, Vickie E
• Leboulleux, Sophie
• Baudin, Eric
• Paci, Angelo
• Deroussent, Alain
• Schlumberger, Martin
• Antoun, Sami

Titel

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

Ist Teil von

• The journal of clinical endocrinology and metabolism, 2013-06, Vol.98 (6), p.2401-2408

Ort / Verlag

Bethesda, MD: Endocrine Society

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Objectives: 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 cm2/m2 (∼0.7 kg) of SM (P = 0.009), and 4.5 cm2/m2 (∼0.5 kg) of SAT (P = 0.004) and gained more VAT, 5.1 cm2/m2 (∼0.7 kg) (P = 0.02). Patients with DLT had lower SM index (37.2 vs 44.3 cm2/m2, P = 0.003) and a higher vandetanib serum concentration (1091 vs 739 ng/mL, P = 0.03). Patients with SM index <43.1 cm2/m2 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.