一项关于口服NEPA用于儿童癌症患者化疗所致恶心呕吐的2期药代动力学和药效学剂量探索研究。
完整摘要 · 中文译文
目的：化疗引起的恶心呕吐（CINV）仍然是儿科肿瘤学中的一个重大挑战，指导最佳止吐方案的资料有限。本2期研究评估了口服奈妥匹坦联合口服帕洛诺司琼（NEPA）在接受高度或中度致吐性化疗的儿科患者中的药代动力学（PK）、药效学、疗效和安全性。 方法：在这项多中心、随机、双盲、剂量探索研究中，儿科患者（<18岁）按年龄、化疗致吐性和方案分层。患者接受两种奈妥匹坦剂量（1.33或4 mg/kg）之一联合帕洛诺司琼（20 µg/kg）。疗效通过急性期（0-24小时）、延迟期（>24-120小时）和总体期（0-120小时）的完全缓解（CR；无呕吐且未使用补救药物）进行评估。PK参数来源于奈妥匹坦、其代谢物和帕洛诺司琼的血浆浓度。通过不良事件和临床评估监测安全性。 结果：在65例可评价患者中，较低奈妥匹坦剂量组的急性期、延迟期和总体期CR率分别为85.3%、70.6%和70.6%，较高剂量组分别为87.1%、71.0%和67.7%。CR在各年龄组和化疗致吐性中基本一致。在延迟期观察到较高的奈妥匹坦暴露（AUC0-inf）与CR增加呈趋势。安全性特征与细胞毒性化疗的预期一致，未观察到新的安全性信号。 结论：单次口服4 mg/kg奈妥匹坦联合口服帕洛诺司琼用于儿童患者化疗所致恶心呕吐（CINV）预防有效且耐受性良好，支持在该人群中进一步研究NEPA。 试验注册：NCT03204279 [注册日期：2017年7月2日]。
完整摘要 · 英文原文
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) remains a significant challenge in pediatric oncology, with limited data guiding optimal antiemetic regimens. This phase 2 study evaluated pharmacokinetics (PK), pharmacodynamics, efficacy, and safety of oral netupitant combined with oral palonosetron (NEPA) in pediatric patients receiving highly or moderately emetogenic chemotherapy. METHODS: In this multicenter, randomized, double-blind, dose-finding study, pediatric patients (< 18 years) were stratified by age, chemotherapy emetogenicity, and schedule. Patients received one of two netupitant doses (1.33 or 4 mg/kg) with palonosetron (20 µg/kg). Efficacy was assessed via complete response (CR; no emesis and no rescue medication) during acute (0-24h), delayed (> 24-120h), and overall (0-120h) phases. PK parameters were derived from plasma concentrations of netupitant, its metabolites, and palonosetron. Safety was monitored through adverse events and clinical assessments. RESULTS: Among 65 evaluable patients, CR rates were 85.3%, 70.6%, and 70.6% in the lower netupitant dose group, and 87.1%, 71.0%, and 67.7% in the higher dose group, for the acute, delayed, and overall phases, respectively. CR was mostly consistent across age groups and chemotherapy emetogenicity. A trend toward increased CR with higher netupitant exposure (AUC0-inf) was observed in the delayed phase. The safety profile was consistent with expectations for cytotoxic chemotherapy, and no new safety signals were observed. CONCLUSION: A single dose of 4 mg/kg oral netupitant with oral palonosetron was effective and well-tolerated for CINV prevention in pediatric patients, supporting further investigation of NEPA in this population. TRIAL REGISTRATION: NCT03204279 [2 July 2017 registration date].