Association of QT interval-prolonging drugs with clinical trial eligibility in patients with advanced cancer.
Association of QT interval-prolonging drugs with clinical trial eligibility in patients with advanced cancer.
复制标题
DOI：
10.3389/fcvm.2022.894623
复制
发表时间：
2022
影响因子：
3.6
通讯作者：
Skaar, Todd C.
中科院分区：
文献类型：
--
作者：
Rowe, Elizabeth J.;Shugg, Tyler;Ly, Reynold C.;Philips, Santosh;Rosenman, Marc B.;Callaghan, John T.;Radovich, Milan;Overholser, Brian R.;Schneider, Bryan P.;Tisdale, James E.;Skaar, Todd C.
药物引起的心率校正QT间期(QTC)延长与潜在致命性尖端心律失常的风险增加有关。由于心律失常的风险，癌症治疗的临床试验通常根据QT间期延长的阈值排除患者。我们的目的是评估在一组晚期癌症患者中，延长QT间期药物的处方与达到癌症试验排除QTC阈值的几率之间的关系。我们对271名在我们机构分子实体肿瘤诊所就诊的患者的电子健康记录进行了回顾。收集的数据包括人口统计学、QTC测量、与室性心律失常相关的诊断以及所有住院和门诊处方。评估了人口统计学和临床变量之间的潜在关联，包括延长QT间期药物的处方和QTC测量。女性QTc值的中位数比男性更长(p=0.030)，在研究期间，女性服用了更多延长QT的药物(p=0.010)。在所有患者中，QT间期延长药物的处方与多个评估时间点(即QT间期测量10、30、60和90天内开出的延长QT间期药物)的中位数和最大QTc值延长有关。同样，开出的延长QT的药物的数量与多个时间点较长的中位数和最大QTc值相关。常见的QTC相关排除标准收集自最近癌症临床试验的ClinicalTrials.gov综述。根据共同排除标准，延长QT的药物处方增加了试验排除的几率。这项研究表明，服用延长QT间期药物的处方与较长的QTc值和更高的被排除在癌症临床试验之外的几率相关。
Drug-induced prolongation of the heart rate-corrected QT interval (QTc) is associated with increased risk for the potentially fatal arrhythmia torsades de pointes. Due to arrhythmia risk, clinical trials with cancer therapeutics often exclude patients based on thresholds for QTc prolongation. Our objective was to assess associations between prescriptions for QT-prolonging drugs and the odds of meeting cancer trial exclusionary QTc thresholds in a cohort of adults with advanced cancer. Electronic health records were retrospectively reviewed for 271 patients seen at our institutional molecular solid tumor clinic. Collected data included demographics, QTc measurements, ventricular arrhythmia-related diagnoses, and all inpatient and outpatient prescriptions. Potential associations were assessed between demographic and clinical variables, including prescriptions for QT-prolonging drugs, and QTc measurements. Women had longer median QTc measurements than men (p = 0.030) and were prescribed more QT-prolonging drugs during the study (p = 0.010). In all patients, prescriptions for QT-prolonging drugs were associated with longer median and maximum QTc measurements at multiple assessed time points (i.e., for QT-prolonging drugs prescribed within 10, 30, 60, and 90 days of QTc measurements). Similarly, the number of QT-prolonging drugs prescribed was correlated with longer median and maximum QTc measurements at multiple time points. Common QTc-related exclusionary criteria were collected from a review of ClinicalTrials.gov for recent cancer clinical trials. Based on common exclusion criteria, prescriptions for QT-prolonging drugs increased the odds of trial exclusion. This study demonstrates that prescriptions for QT-prolonging drugs were associated with longer QTc measurements and increased odds of being excluded from cancer clinical trials.
登录
查看更多内容
影响因子：
2.8
作者：
Burke, JH;Ehlert, FA;Kadish, AH
通讯作者：
Kadish, AH
影响因子：
3.6
作者：
Tri Le;Yang, Hui;Gerber, David E.
通讯作者：
Gerber, David E.
影响因子：
24
作者：
Drew, Barbara J.;Ackerman, Michael J.;Funk, Marjorie;Gibler, W. Brian;Kligfield, Paul;Menon, Venu;Philippides, George J.;Roden, Dan M.;Zareba, Wojciech
通讯作者：
Zareba, Wojciech
影响因子：
3.6
作者：
Kim P;Masha L;Olson A;Iliescu C;Karimzad K;Hassan S;Palaskas N;Durand JB;Leung CH;Lopez-Mattei J
通讯作者：
Lopez-Mattei J
影响因子：
2.9
作者：
Khan, Qasim;Ismail, Mohammad;Khan, Sehrash
通讯作者：
Khan, Sehrash