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
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
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DOI：
10.1210/jc.2013-1115
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发表时间：
2013-06-01
影响因子：
5.8
通讯作者：
Antoun, Sami
中科院分区：
文献类型：
--
作者：
Massicotte, Marie-Helene;Borget, Isabelle;Antoun, Sami
目的：Vandetanib被美国食品和药物协会批准用于晚期甲状腺髓样癌（MTC）的治疗。由于在MTC中观察到体重（BW）下降，并且由于低骨骼肌质量（SM）与药物毒性有关，因此本研究评估了vandetanib对SM和脂肪组织（AT）的影响，并探讨了SM、毒性和vandetanib血清浓度之间的关系。方法：在ZETA研究中，33例MTC患者接受万德替尼（n = 23）或安慰剂（n = 10）治疗。内脏AT （VAT）、sc AT （SAT）和SM通过测量组织横截面积（每平方米平方厘米）进行计算机断层成像评估。前瞻性记录剂量限制毒性（dlt）。结果：在3个月早期，与体重、肌肉和SAT下降的安慰剂组相比，vandetanib治疗的患者体重增加1.5 kg (P = 0.02)， SM增加1.3 cm(2)/m(2)（类似于0.7 kg） （P = 0.009）， SAT增加4.5 cm(2)/m(2)（类似于0.5 kg） （P = 0.004）， VAT增加更多，5.1 cm(2)/m(2)（类似于0.7 kg） （P = 0.02）。DLT患者SM指数较低(37.2 vs 44.3 cm(2)/m(2), P = 0.003)， vandetanib血清浓度较高（1091 vs 739 ng/mL, P = 0.03）。SM指数< 43.1 cm(2)/m(2)的患者发生DLT的概率较高（73% vs 14%, P = 0.004），万德替尼血清浓度较高（1037 vs 745 ng/mL, P = 0.04）。vandetanib血清浓度最高的患者与中低水平的患者相比，DLT发生率更高，分别为78% vs 40% vs 20% （P = 0.04）。结论：万德替尼治疗3个月后肌肉和脂肪组织恢复。肌肉质量低的患者血清万德他尼浓度高，毒性发生率高。
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). Doselimiting 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) (similar to 0.7 kg) of SM (P = 0.009), and 4.5 cm(2)/m(2) (similar to 0.5 kg) of SAT (P = 0.004) and gained more VAT, 5.1 cm(2)/m(2) (similar to 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.