Galetta Fabio, Franzoni Ferdinando, Cervetti Giulia, Cecconi Nadia, Carpi Angelo, Petrini Mario, Santoro Gino
Department of Internal Medicine, University of Pisa School of Medicine, Via Roma, 67, Italy.
Biomed Pharmacother. 2005 Dec;59(10):541-4. doi: 10.1016/j.biopha.2004.12.003. Epub 2005 Oct 21.
Aim of the present study was to assess the effect of epirubicin-based chemotherapy on QT interval dispersion in patients with aggressive non-Hodgkin lymphoma (NHL), and the effect of dexrazoxane supplementation. Prolongation of QT dispersion may not only represent a sensitive tool in identifying the first sign of anthracycline-induced cardiotoxicity, but it may serve also in identifying patients who are at risk of arrhythmic events.
Twenty untreated patients, <or=60 years of age with newly-diagnosed aggressive NHL, eligible for a treatment with epirubicin-based chemotherapy were selected for the study. The patients were randomly allocated in two subgroups (N=10) to receive or not dexrazoxane hydrochloride (400 mg/m(2)) after epirubicin infusion. The patients underwent 12-lead electrocardiogram (ECG) before and after epirubicin infusion and after dexrazoxane supplementation. QT dispersion was defined as the difference between the maximum and the minimum QT interval occurring in any of the 12 ECG leads, corrected (QTc) for heart rate.
All the 20 patients showed increased QT dispersion (44.3 +/- 8.4 vs. 68.4+/-11.4 ms, P<0.001) and QTc dispersion (46.2 +/- 6.2 vs. 72.2 +/- 8.4, P<0.001) after chemotherapy infusion. The 10 patients who underwent supplementation with dexrazoxane exhibited a significant reduction of QT dispersion (67.4 +/- 8.1 vs. 49.5 +/- 4.2 ms, P<0.001) and QTc dispersion (71.2 +/- .7 vs. 51.4 +/- 4.3 ms, P<0.001), while the 10 patients not supplemented with dexrazoxane did not (QT dispersion: 69.3 +/- 7.6 vs. 64.2 +/- 6.9 ms; QTc dispersion: 72.8 +/- 8.1 vs. 67.3 +/- 7.2 ms, ns).
Epirubicin-based chemotherapy causes an early increase of the QT and QTc dispersion, which is attenuated by dexrazoxane supplementation. Therefore, dexrazoxane can reduce the arrhythmic risk in patients treated with epirubicin.
本研究旨在评估以表柔比星为基础的化疗对侵袭性非霍奇金淋巴瘤（NHL）患者QT间期离散度的影响，以及补充右丙亚胺的效果。QT离散度延长不仅可能是识别蒽环类药物所致心脏毒性首个迹象的敏感工具，还可用于识别有发生心律失常事件风险的患者。
选取20例年龄≤60岁、新诊断为侵袭性NHL且适合接受以表柔比星为基础化疗的未治疗患者进行研究。患者被随机分为两个亚组（每组10例），在输注表柔比星后分别接受或不接受盐酸右丙亚胺（400mg/m²）。患者在输注表柔比星前、后以及补充右丙亚胺后进行12导联心电图（ECG）检查。QT离散度定义为12个ECG导联中任意导联出现的最大QT间期与最小QT间期之差，并根据心率进行校正（QTc）。
所有20例患者化疗输注后QT离散度（44.3±8.4对68.4±11.4ms，P<0.001）和QTc离散度（46.2±6.2对72.2±8.4，P<0.001）均增加。接受右丙亚胺补充的10例患者QT离散度（67.4±8.1对49.5±4.2ms，P<0.001）和QTc离散度（71.2±.7对51.4±4.3ms，P<0.001）显著降低，而未接受右丙亚胺补充的10例患者则未降低（QT离散度：69.3±7.6对64.2±6.9ms；QTc离散度：72.8±8.1对67.3±7.2ms，无显著性差异）。
以表柔比星为基础的化疗导致QT和QTc离散度早期增加，补充右丙亚胺可使其减弱。因此，右丙亚胺可降低接受表柔比星治疗患者的心律失常风险。
