Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients
Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients
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DOI：
10.1093/annonc/mdf132
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发表时间：
2002-05-01
影响因子：
50.5
通讯作者：
Nielsen, SL
中科院分区：
文献类型：
--
作者：
Jensen, BV;Skovsgaard, T;Nielsen, SL
背景：随着剂量的增加，高杀瘤活性的蒽环类药物会引起心脏损害，根据经验药物限制，大约10-15%的患者会在两年内发展为充血性心力衰竭，死亡率接近50%，仅用洋地黄利尿剂治疗。为了避免CHF，有一项共识的建议，即心功能监测应密切结合使用蒽环类药物。由于没有进行更大系列的前瞻性研究，这些建议是基于对少数患者的回顾数据。患者和方法：在一项前瞻性、盲法观察研究中，120名晚期乳腺癌患者在表柔比星治疗前、期间和中位数3年后进行了跟踪调查。他们进行了604次连续的左心室射血分数(LVEF)放射性核素测量，这些测量结果没有经过计算就被储存起来，除了出现明确的CHF的患者。结果：蒽环类药物的心脏毒性与累积剂量密切相关，个体敏感性差异很大，并随着年龄的增长而急剧增加。在延迟起病3个月或更长时间的情况下，表柔比星在治疗数年后持续引起心功能的威胁、缓慢的进行性恶化。精算估计有59%的患者在服用表柔比星850-1000 mg/m(2)后的3年内左心室射血分数相对下降25%，20%的患者恶化为CHF。患者未自发恢复心功能，而持续应用昼夜节律血管紧张素转换酶抑制剂治疗3个月以上可显著恢复心功能，且持续时间长。结论：由于心脏毒性表现的移位，与服用蒽环类药物密切相关的功能监测似乎是一种效果不佳的方法，但后期监测是必要的。因此，应修订目前的监测建议。
Background: With increasing doses the highly tumoricidal anthracycline drugs cause heart damage, Based on empirical drug limitations about 10-15% of patients will develop congestive heart failure (CHF) with a mortality of similar to50% within 2 years on digitalo-diuretic therapy alone. To avoid CHF there is a consensus recommendation that cardiac function should be monitored in close connection with anthracycline administration. As no prospective studies in a larger series have been performed, these recommendations are based on retrospective data on small numbers of patients.Patients and methods: In a prospective, blinded observational study 120 patients with advanced breast cancer were followed before, during, and a median 3 years after treatment with epirubicin. They had 604 serial radionuclide measurements of left ventricular ejection fraction (LVEF) that were stored without calculations except in patients who developed a well-defined CHF.Results: Anthracycline cardiotoxicity was closely correlated with the cumulative dose, with a great variability in individual susceptibility and a dramatic increase with advancing age. With a delayed onset of 3 months or more, epirubicin induced a threatening, slowly progressive deterioration of cardiac function continuing years after treatment. An actuarial estimation of 59% of the patients experienced a 25% relative reduction in LVEF 3 years after 850-1000 mg/m(2) of epirubicin and 20% had deteriorated into a CHF. The patients did not spontaneously regain cardiac function whereas continued therapy with a circadian angiotensin-converting enzyme inhibitor for more than 3 months caused a remarkably potent and long-lasting recovery.Conclusions: Due to the displaced cardiotoxic manifestation, functional monitoring in close connection with anthracycline administration appears to be a poorly effective method while later monitoring is essential. Current monitoring recommendations should therefore be revised.