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表柔比星、环磷酰胺和多西他赛治疗后乳腺癌患者QTc间期延长的评估及观察者间变异的影响

Evaluation of QTc Interval Prolongation in Breast Cancer Patients after Treatment with Epirubicin, Cyclophosphamide, and Docetaxel and the Influence of Interobserver Variation.

作者信息

Puppe Julian, van Ooyen Deborah, Neise Jeanne, Thangarajah Fabinshy, Eichler Christian, Krämer Stefan, Pfister Roman, Mallmann Peter, Wirtz Marina, Michels Guido

机构信息

Department of Gynaecology and Obstetrics, University Hospital Cologne, Cologne, Germany.

CIO Center for Integrated Oncology Cologne/Bonn, Bonn, Germany.

出版信息

Breast Care (Basel). 2017 Mar;12(1):40-44. doi: 10.1159/000455065. Epub 2017 Jan 18.

Abstract

BACKGROUND

Chemotherapy with anthracyclines is associated with life-threatening electrocardiographic alterations including corrected QT (QTc) interval prolongation.

PATIENTS AND METHODS

In this study we assessed the effect of epirubicin, cyclophosphamide, and docetaxel (EC-Doc) on the QTc interval in 10 patients with early breast cancer. Cardiac toxicity was assessed with symptoms, transthoracic echocardiography, electrocardiography (ECG), and serum cardiac markers at baseline and after 4 cycles of EC and 4 cycles of docetaxel. To evaluate the influence of interobserver variation, the QTc interval was analyzed by a cardiologist, a gynecologist, and with automated ECG interpretation software.

RESULTS

There was a significant QTc prolongation after EC treatment independent of the investigator. In addition, a significant increase in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels was noted after EC treatment. QTc prolongation and NT-proBNP levels normalized after docetaxel treatment. Other biochemical markers were within normal ranges. No clinically relevant effect on left ventricular ejection fraction was observed.

CONCLUSION

This prospective study demonstrated that EC treatment increases the QTc interval and NT-proBNP levels in women with early breast cancer. This effect was reversible and independent of docetaxel administration. Moreover, the treating physician can safely perform QTc interval evaluation as part of clinical routine independent of his/her specialty. Due to the small number of patients, further conclusions are limited at this point.

摘要

背景

蒽环类药物化疗与危及生命的心电图改变有关,包括校正QT(QTc)间期延长。

患者与方法

在本研究中,我们评估了表柔比星、环磷酰胺和多西他赛(EC-多西他赛)对10例早期乳腺癌患者QTc间期的影响。在基线时以及EC治疗4个周期和多西他赛治疗4个周期后,通过症状、经胸超声心动图、心电图(ECG)和血清心脏标志物评估心脏毒性。为了评估观察者间差异的影响,由心脏病专家、妇科医生以及使用自动ECG解读软件分析QTc间期。

结果

EC治疗后出现了与研究者无关的显著QTc延长。此外,EC治疗后观察到脑钠肽前体N末端(NT-proBNP)水平显著升高。多西他赛治疗后QTc延长和NT-proBNP水平恢复正常。其他生化标志物在正常范围内。未观察到对左心室射血分数有临床相关影响。

结论

这项前瞻性研究表明,EC治疗会增加早期乳腺癌女性的QTc间期和NT-proBNP水平。这种效应是可逆的,且与多西他赛给药无关。此外,治疗医生可作为临床常规的一部分安全地进行QTc间期评估,而与他/她的专业无关。由于患者数量较少,目前进一步的结论有限。

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Breast cancer therapy-associated cardiovascular disease.乳腺癌治疗相关的心血管疾病。
Nat Rev Clin Oncol. 2016 Mar;13(3):172-84. doi: 10.1038/nrclinonc.2015.171. Epub 2015 Nov 24.

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