Cambridge University Health Partners, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK,
Invest New Drugs. 2013 Oct;31(5):1283-93. doi: 10.1007/s10637-013-9962-7. Epub 2013 Apr 27.
Some targeted anticancer agents are associated with serious ventricular tachyarrhythmias, which may be predicted by electrocardiographic evaluation of drug-related QT prolongation. We studied the effects of nintedanib (BIBF 1120; an oral, triple angiokinase inhibitor targeting vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptors) on the QT interval in patients with renal cell carcinoma (RCC) participating in an open-label phase II trial.
Treatment-naïve, adult patients with unresectable/metastatic, clear cell RCC received nintedanib 200 mg twice daily. QT intervals were evaluated at baseline (day -1), on day 1 (after the first dose), and on day 15 (steady state) by 12-lead electrocardiograms (ECGs) performed in triplicate. Pharmacokinetic sampling was also undertaken.
Among 64 evaluable patients, the upper limits of the 2-sided 90 % confidence intervals for the adjusted mean time-matched changes in QTcF interval (corrected for heart rate by Fridericia's method) from baseline to day 1 and 15 (primary ECG endpoint) were well below the regulatory threshold of 10 ms at all times. No relationship between nintedanib exposure and change from baseline in QTcF was seen. Nintedanib was generally well tolerated with no drug-related cardiovascular adverse events.
Nintedanib administered at 200 mg twice daily was not associated with clinically relevant QT prolongation.
一些靶向抗癌药物与严重的室性心动过速有关，这可能通过药物相关 QT 延长的心电图评估来预测。我们研究了尼达尼布（BIBF 1120；一种口服的、针对血管内皮生长因子、成纤维细胞生长因子和血小板衍生生长因子受体的三激酶抑制剂）对接受开放标签 II 期试验的肾细胞癌（RCC）患者 QT 间期的影响。
未经治疗的、成年、不可切除/转移性、透明细胞 RCC 患者每天接受尼达尼布 200 mg，每日两次。在基线（第-1 天）、第 1 天（第一次给药后）和第 15 天（稳态）通过重复进行 12 导联心电图（ECG）评估 QT 间期。还进行了药代动力学采样。
在 64 名可评估的患者中，从基线到第 1 天和第 15 天（主要心电图终点），校正后的平均时间匹配的 QTcF 间隔（用 Fridericia 法校正心率）的双侧 90%置信区间上限在任何时候都远低于 10 毫秒的监管阈值。在尼达尼布暴露与 QTcF 从基线的变化之间没有关系。尼达尼布通常耐受性良好，无药物相关的心血管不良事件。
尼达尼布每天两次 200mg 给药与临床相关的 QT 延长无关。
