Cardiac studies in patients treated with depsipeptide, FK228, in a phase II trial for T-cell lymphoma
Cardiac studies in patients treated with depsipeptide, FK228, in a phase II trial for T-cell lymphoma
复制标题
DOI：
10.1158/1078-0432.ccr-05-2095
复制
发表时间：
2006-06-15
影响因子：
11.5
通讯作者：
Bates, Susan E.
中科院分区：
文献类型：
--
作者：
Piekarz, Richard L.;Frye, A. Robin;Bates, Susan E.
目的：组蛋白脱乙酰酶抑制剂缩酚肽 (FK228) 对皮肤或外周 T 细胞淋巴瘤患者具有活性。心电图异常被认为是一种类别效应，在临床前动物研究和 I 期测试中观察到，并导致在一项正在进行的疗效试验中纳入强化心脏监测。 患者和方法：本报告总结了 42 名入组并接受 Depsipepticle II 期试验的患者的心脏监测。心脏评估包括连续心电图以评估 T 波、ST 段和 QT 间期影响，以及连续血清心肌肌钙蛋白 I 水平和左心室射血分数 (LVEF) 评估以排除心肌损伤。 结果：来自 282 个周期和 736 剂抗抑郁药的心脏研究包括 2,051 份心电图和 161 份 LVEF 评估。尽管在治疗后获得的心电图中观察到 T 波平坦（1 级）或 ST 段压低（2 级），但这些心电图异常与心肌肌钙蛋白 I 升高或左心室功能改变无关。即使在 16 名接受治疗≥ 6 个月的患者中，无论之前是否接触过蒽环类药物，也没有观察到 LVEF 的显着变化。治疗后心电图显示，与基线相比，平均心率校正 QT 间期延长了 14.4 毫秒。已经制定了电解质替代方案以减轻潜在的不良影响。结论：本研究中获得的数据表明，服用抗消化剂与心肌损伤或心功能受损无关。心率校正 QT 间期延长的潜在影响仍在研究中。
Purpose: The histone deacetylase inhibitor depsipeptide (FK228) has activity in patients with cutaneous or peripheral T-cell lymphoma. Electrocardiogram abnormalities, thought to be a class effect, were observed in preclinical animal studies and phase I testing and led to the incorporation of intensive cardiac monitoring in an ongoing efficacy trial.Patients and Methods: This report summarizes the cardiac monitoring of 42 patients enrolled and treated on a phase II trial with depsipepticle. Cardiac evaluations included serial electrocardiograms to evaluate T-wave, ST segment, and QT interval effects and serial serum cardiac troponin I levels and left ventricular ejection fraction (LVEF) evaluations to exclude myocardial damage.Results: Cardiac studies from 282 cycles and 736 doses of depsipepticle included 2,051 electrocardiograms and 161 LVEF evaluations. Although T-wave flattening (grade 1) or ST segment depression (grade 2) was observed in more than half of the electrocardiograms obtained posttreatment, these electrocardiogram abnormalities were not associated with elevation of cardiac troponin I or with altered left ventricular function. No significant changes in LVEF were observed, even in 16 patients treated for >= 6 months and regardless of prior anthracycline exposure. Posttreatment electrocardiograms had a mean heart rate-corrected QT interval prolongation of 14.4 milliseconds compared with baseline. Electrolyte replacement has been instituted to mitigate potential untoward effects.Conclusion: The data obtained in this study show that the administration of depsipepticle is not associated with myocardial damage or impaired cardiac function. The potential effect of heart rate-corrected QT interval prolongation remains under study.