Doxorubicin administration by continuous infusion is not cardioprotective: The Dana-Farber 91-01 acute lymphoblastic leukemia protocol
Doxorubicin administration by continuous infusion is not cardioprotective: The Dana-Farber 91-01 acute lymphoblastic leukemia protocol
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DOI：
10.1200/jco.20.6.1677
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发表时间：
2002-03-15
影响因子：
45.3
通讯作者：
Colan, SD
中科院分区：
文献类型：
--
作者：
Lipshultz, SE;Giantris, AL;Colan, SD
目的：急性阿霉素诱导的心脏毒性可以通过持续输注药物来预防，但儿童心脏毒性的机制不同。我们比较了接受推注或持续输注阿霉素的儿童的心脏结局。患者和方法：在一项随机研究中，高危急性淋巴细胞白血病儿童接受阿霉素360 mg/m2，剂量为30 mg/m2，每3周一次，推注（1小时内，n = 57）或持续输注（超过48小时，n = 64）。超声心动图之前获得的阿霉素，并在最长的后续时间进行了集中重新测量，并计算心脏测量的Z分数的基础上，健康population.Results：各组在年龄，性别分布，阿霉素剂量和随访时间相似。治疗前，左心室（LV）结构和功能的测量结果未显示扩张性心肌病，推注组和连续输注组之间无统计学差异。随访超声心动图显示两组之间的任何心脏特征均无显著差异，但与正常和基线相比，两组均显示LV结构和功能明显异常。例如，在两次超声心动图之间，两组的平均左心室短缩分数均下降约2个标准差。两组的左心室收缩力均受到抑制（推注组患者，中位z评分= -0.70 SD，P = 0.006;连续输注组患者，中位z评分=-0.765，P = 0.005）。在两组中均观察到扩张性心肌病和左心室肥厚不充分。临床心脏表现和事件无survivaldids.Conclusion：连续阿霉素输注超过48小时的儿童白血病并没有提供一个心脏保护的优势，推注。两种方案均与进行性亚临床心脏毒性相关。应探索其他心脏保护策略。
Purpose: Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug, but mechanisms of cardiotoxicity are different in children. We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin.Patients and Methods: In a randomized study, children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m(2) in 30-mg/m(2) doses every 3 weeks either by bolus (within 1 hour, n = 57) or by continuous infusion (over 48 hours, n = 64). Echocardiograms obtained before doxorubicin and at longest follow-up times were centrally remeasured, and z scores of cardiac measurements were calculated based on a healthy population.Results: The groups were similar in age, sex distribution, doxorubicin dose, and duration of follow-up. Before treatment, measures of left ventricular (LV) structure and function did not reveal dilated cardiomyapathy and were not statistically different between bolus and continuous-infusion groups. The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic, but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline. For example, the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms. LV contractility was depressed in both groups (for bolus patients, median z score = -0.70 SD, P = .006; for continuous-infusion patients, median z score = -0.765, P = .005). Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups. Clinical cardiac manifestations and event-free survival did not differ.Conclusion: Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion. Both regimens were associated with progressive subclinical cardiotoxicity. Other cardioprotective strategies should be explored.