The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS Kaposi's sarcoma patients treated with pegylated liposomal doxorubicin
The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS Kaposi's sarcoma patients treated with pegylated liposomal doxorubicin
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DOI：
10.1023/a:1008216430806
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发表时间：
1998-07-01
影响因子：
50.5
通讯作者：
Martin, FJ
中科院分区：
文献类型：
--
作者：
Berry, G;Billingham, M;Martin, FJ
背景资料：在临床前模型中，聚乙二醇化脂质体阿霉素（PL-DOX）诱导的心脏毒性低于非脂质体阿霉素。Endomyosis活检是一种高度敏感和特异性的方法检测蒽环类药物引起的心脏damage.Patients和方法：心肌组织从10个KS患者谁收到了累积PL-DOX（20毫克/平方米（2）/每两周）440-840毫克/平方米（2）蒽环类药物引起的心脏损害的证据进行了评估。对照组来自在两个早期心脏活检方案中接受累积阿霉素剂量为174-671 mg/m2的患者。根据累积剂量（+/-10 mg/m2）和多柔比星峰值剂量（60或20 mg/m2，对照组1）或单独峰值剂量（20 mg/m2，对照组2）选择两个对照组。PL-DOX组和阿霉素组的中位活检评分分别为0.3和3.0（P = 0.002，Cochran-Mantel-Haenszel行平均差异检验），组1，组2为1.25（P <0.001，Wilcoxon秩和检验）。相对于给予可比累积剂量的多柔比星的历史对照患者，给予PL-DOX的患者中观察到较不严重的心脏变化。
Background: Pegylated liposomal doxorubicin (PL-DOX) has been shown in preclinical models to induce less cardiotoxicity than non-liposomal doxorubicin. Endomyocardial biopsy is a highly sensitive and specific method for detecting anthracycline-induced cardiac damage.Patients and methods: Myocardial tissue from ten KS patients who had received cumulative PL-DOX (20 mg/m(2)/bi-weekly) of 440-840 mg/m(2) was evaluated for evidence of anthracycline-induced cardiac damage. Controls were assembled from patients who had received cumulative doxorubicin doses of 174-671 mg/m(2) in two earlier cardiac biopsy protocols. Two control groups were selected on the basis of both cumulative (+/-10 mg/m(2)) and peak doxorubicin dose (60 or 20 mg/m(2), control group 1), or peak dose alone (20 mg/m(2), control group 2).Results: PL-DOX patients had significantly lower biopsy scores compared with those of doxorubicin controls despite higher cumulative doses of anthracycline. The median biopsy scores for the PL-DOX and doxorubicin groups, respectively, were 0.3 vs. 3.0 (P = 0.002, Cochran-Mantel-Haenszel row mean difference test) for group 1 and 1.25 for group 2 (P < 0.001,Wilcoxon rank-sum test).Conclusions: Less severe cardiac changes were seen in patients given PL-DOX relative to historical control patients given comparable cumulative doses of doxorubicin.