低剂量表柔比星与多柔比星心脏毒性的比较：通过放射性核素血管造影术研究舒张和收缩参数的变化
Comparison of epirubicin and doxorubicin cardiotoxicity induced by low doses: evolution of the diastolic and systolic parameters studied by radionuclide angiography.
作者信息
Cottin Y, Touzery C, Dalloz F, Coudert B, Toubeau M, Riedinger A, Louis P, Wolf J E, Brunotte F
机构信息
Centre de Cardiologie, Hôpital du Bocage, Dijon, France.
出版信息
Clin Cardiol. 1998 Sep;21(9):665-70. doi: 10.1002/clc.4960210911.
BACKGROUND
Previous studies have demonstrated that epirubicin (EPI) has a lower propensity to produce cardiotoxic effects than doxorubicin (DXR) at high doses.
HYPOTHESIS
The aim of the study was to compare the cardiotoxicity induced by low doses of EPI and DXR in patients before and 1 month after the end of chemotherapy.
METHOD
In a prospective study, 99 patients with a mean age of 51 +/- 12 years and without cardiac disease were studied before and 1 month after the end of chemotherapy. Group 1 included 38 patients receiving 246 +/- 96 mg/m2 of DXR and Group 2 included 61 patients receiving EPI with and equivalent dose of 219 +/- 92 mg/m2 of DXR. Ejection fraction (EF) of the left ventricle (LV), peak ejection rate (PER), and peak filling rate (PFR) [expressed in end-diastolic volume/s (EDV/s)] were evaluated by gated radionuclide angiography; PFR/PER were also calculated.
RESULTS
Moderate and similar alterations of left ventricular ejection fraction were shown for low doses of anthracyclines. The EF of the LV decreased from 57 +/- 6% to 54 +/- 6% for DXR group (Group 1) (p = 0.005), and from 58 +/- 5% to 55 +/- 5% for the EPI group (Group 2)(p = 0.001). The PER of the left ventricle fell from 3.08 +/- 0.46 EDV/s to 2.79 +/- 0.49 in Group 1 (p = 0.004) and from 2.98 +/- 0.50 to 2.73 +/- 0.34 EDV/s in Group 2 (p = 0.001). In contrast, no significant alteration of PFR appeared in Group 2 (from 2.72 +/- 0.51 to 2.62 +/- 0.41 EDV/s) for the equivalent dose of anthracycline, while PFR of the LV dropped from 2.82 +/- 0.76 (EDV/s) to 2.41 +/- 0.55 after doxorubicin (p = 0.004). No difference was found between 1 and 12 months after the end of the treatment in 25 patients in Group 1 and 28 patients in Group 2. These results confirm the advantage of EPI over DXR in terms of cardiotoxicity and help explain the relationship of cellular damage mechanisms with the functional parameters of nuclear investigation.
CONCLUSION
A possible explanation for specific alteration after DXR could be the increased production of semiquinone free radicals, which are known to induce membrane damage and, consequently, myocardial edema and diastolic alteration.
背景
先前的研究表明，高剂量时表柔比星（EPI）产生心脏毒性作用的倾向低于多柔比星（DXR）。
假设
本研究的目的是比较低剂量EPI和DXR在化疗结束前及结束后1个月对患者心脏毒性的影响。
方法
在一项前瞻性研究中，对99例平均年龄为51±12岁且无心脏病的患者在化疗结束前及结束后1个月进行了研究。第1组包括38例接受246±96mg/m² DXR的患者，第2组包括61例接受等效剂量219±92mg/m² DXR的EPI的患者。通过门控放射性核素血管造影评估左心室（LV）的射血分数（EF）、峰值射血率（PER）和峰值充盈率（PFR）[以舒张末期容积/秒（EDV/s）表示]；还计算了PFR/PER。
结果
低剂量蒽环类药物显示出左心室射血分数的中度且相似改变。DXR组（第1组）的LV-EF从57±6%降至54±6%（p = 0.005），EPI组（第2组）从58±5%降至55±5%（p = 0.001）。第1组左心室的PER从3.08±0.46 EDV/s降至2.79±0.49（p = 0.004），第2组从2.98±0.50降至2.73±0.34 EDV/s（p = 0.001）。相比之下，对于等效剂量的蒽环类药物，第2组的PFR无显著改变（从2.72±0.51降至2.62±0.41 EDV/s），而多柔比星治疗后LV的PFR从2.82±0.76（EDV/s）降至2.41±0.55（p = 0.004）。第1组的25例患者和第2组的28例患者在治疗结束后1个月和12个月之间未发现差异。这些结果证实了EPI在心脏毒性方面优于DXR，并有助于解释细胞损伤机制与核检查功能参数之间的关系。
结论
DXR后出现特定改变的一个可能解释是半醌自由基生成增加，已知其可诱导膜损伤，进而导致心肌水肿和舒张功能改变。
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