Department of Pulmonary Medicine, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
J Thorac Oncol. 2023 Aug;18(8):1017-1030. doi: 10.1016/j.jtho.2023.03.020. Epub 2023 Mar 29.
Alectinib is a standard-of-care treatment for metastatic ALK+ NSCLC. Weight gain is an unexplored side effect reported in approximately 10%. To prevent or intervene alectinib-induced weight gain, more insight in its extent and etiology is needed.
Change in body composition was analyzed in a prospective series of 46 patients with ALK+ NSCLC, treated with alectinib. Waist circumference, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle were quantified using sliceOmatic software on computed tomography images at baseline, 3 months (3M), and 1 year (1Y). To investigate an exposure-toxicity relationship, alectinib plasma concentrations were quantified. Four patients with more than 10 kg weight gain were referred to Erasmus MC Obesity Center CGG for in-depth analysis (e.g., assessments of appetite, dietary habits, other lifestyle, medical and psychosocial factors, and extensive metabolic and endocrine assessments, including resting energy expenditure).
Mean increase in waist circumference was 9 cm (9.7%, p < 0.001) in 1Y with a 40% increase in abdominal obesity (p = 0.014). VAT increased to 10.8 cm (15.0%, p = 0.003) in 3M and 35.7 cm (39.0%, p < 0.001) in 1Y. SAT increased to 18.8 cm (12.4%, p < 0.001) in 3M and 45.4 cm (33.3%, p < 0.001) in 1Y. The incidence of sarcopenic obesity increased from 23.7% to 47.4% during 1Y of treatment. Baseline waist circumference was a positive predictor of increase in VAT (p = 0.037). No exposure-toxicity relationship was found. In-depth analysis (n = 4) revealed increased appetite in two patients and metabolic syndrome in all four patients.
Alectinib may cause relevant increased sarcopenic abdominal obesity, with increases of both VAT and SAT, quickly after initiation. This may lead to many serious metabolic, physical, and mental disturbances in long-surviving patients.
阿来替尼是转移性 ALK+ NSCLC 的标准治疗方法。体重增加是约 10%报告的未探索到的副作用。为了预防或干预阿来替尼引起的体重增加，需要更多地了解其程度和病因。
对 46 例接受阿来替尼治疗的 ALK+ NSCLC 患者进行前瞻性系列研究，分析身体成分的变化。使用切片 Omatic 软件，在基线、3 个月（3M）和 1 年（1Y）时对 CT 图像上的腰围、内脏脂肪组织（VAT）、皮下脂肪组织（SAT）和骨骼肌进行定量分析。为了研究暴露与毒性的关系，对阿来替尼的血浆浓度进行了定量。有 4 名体重增加超过 10 公斤的患者被转介到 Erasmus MC 肥胖中心 CGG 进行深入分析（例如，评估食欲、饮食习惯、其他生活方式、医疗和心理社会因素，以及广泛的代谢和内分泌评估，包括静息能量消耗）。
在 1Y 时，腰围平均增加 9 厘米（9.7%，p<0.001），腹部肥胖增加 40%（p=0.014）。3M 时 VAT 增加 10.8 厘米（15.0%，p=0.003），1Y 时增加 35.7 厘米（39.0%，p<0.001）。3M 时 SAT 增加 18.8 厘米（12.4%，p<0.001），1Y 时增加 45.4 厘米（33.3%，p<0.001）。在治疗 1Y 期间，肌肉减少性肥胖的发生率从 23.7%增加到 47.4%。基线腰围是 VAT 增加的正预测因子（p=0.037）。未发现暴露与毒性的关系。深入分析（n=4）显示，两名患者食欲增加，四名患者均患有代谢综合征。
阿来替尼可能会导致快速增加的肌肉减少性腹部肥胖，同时增加 VAT 和 SAT。这可能会导致长期存活患者出现许多严重的代谢、身体和精神障碍。
Zotero 插件