背景:Anamorelin,一种治疗癌症恶病质的药物,结合ghrelin受体,改善体重和食欲。在日本的临床试验中,患者经历了10.7%频率的兴奋剂传导系统抑郁作为严重的副作用。虽然罕见,anamorelin有时会导致致命的心律失常。因为癌症恶病质患者通常体重不足,缺乏关于阿纳瑞林在肥胖患者中安全性的数据.我们报告了一例肥胖的非小细胞肺癌患者在服用anamorelin后QT间期延长的病例。
方法:一名体重指数为30kg/m2的女性患者接受了肺腺癌的免疫治疗。她出现了严重的体重减轻,厌食症,和疲劳。她没有心脏病史。在第12天,每天一次服用100毫克阿纳瑞林后,病人出现恶心,腹泻,和厌食症,这被认为是癌症免疫疗法诱导的免疫相关不良事件,她被送进了医院.入院时的心电图(ECG)显示QTc间隔为502ms。一入场,她的肝功能是Child-PughB级,Anamorelin第二天就被停用了.Anamorelin停药后第3天,QTc间期延长了557ms,然后在第6天降至490ms,在第16天改善至450ms。避免了Anamorelin的再给药。
结论:在给肥胖患者服用阿纳瑞林时,我们应该意识到刺激传导系统抑郁的可能性,如体重不足的患者。因此,我们应该从阿纳瑞林给药的早期开始对患者进行心电图监测。Anamorelin是亲脂性的,肥胖患者的分布量增加。因此,肥胖患者在停用anamorelin后可能会继续有QT间期延长,需要长期的副作用监测。
BACKGROUND: Anamorelin, a drug to treat cancer cachexia, binds to ghrelin receptors and improves body weight and appetite. In clinical trials in Japan, patients experienced a 10.7% frequency of stimulant conduction system depression as a severe side effect. Although rare, anamorelin sometimes causes fatal arrhythmias. Because patients with cancer cachexia are often underweight, data on the safety of anamorelin in obese patients are lacking. We report a
case of QT interval prolongation after anamorelin administration to an obese patient with non-small cell lung cancer.
METHODS: A female patient with a body mass index of 30 kg/m2 underwent immunotherapy for lung adenocarcinoma. She presented with severe weight loss, anorexia, and fatigue. She had no history of heart disease. On day 12, after administration of anamorelin 100 mg once daily, the patient developed nausea, diarrhea, and anorexia, which were considered cancer immunotherapy-induced immune-related adverse events, and she was admitted to the hospital. An electrocardiogram (ECG) on admission showed a
QTc interval of 502 ms. On admission, her hepatic function was Child-Pugh class B, and anamorelin was discontinued the next day. On day 3 after anamorelin discontinuation, the
QTc interval was prolonged by up to 557 ms, then decreased to 490 ms on day 6, and improved to 450 ms on day 16. Re-administration of anamorelin was avoided.
CONCLUSIONS: When administering anamorelin to obese patients, we should be aware of the potential for stimulatory conduction system depression, as in underweight patients. Therefore, we should monitor patients by ECG from the early stages of anamorelin administration. Anamorelin is lipophilic, and its volume of distribution is increased in obese patients. Consequently, obese patients may continue to have QT interval prolongation after discontinuation of anamorelin, requiring long-term side-effect monitoring.