Berry G, Billingham M, Alderman E, Richardson P, Torti F, Lum B, Patek A, Martin F J
Department of Surgical Pathology, Stanford University, CA, USA.
Ann Oncol. 1998 Jul;9(7):711-6. doi: 10.1023/a:1008216430806.
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.
Myocardial tissue from ten KS patients who had received cumulative PL-DOX (20 mg/m2/biweekly) of 440-840 mg/m2 was evaluated for evidence of anthracycline-induced cardiac damage. Controls were assembled from patients who had received cumulative doxorubicin doses of 174-671 mg/m2 in two earlier cardiac biopsy protocols. Two control groups were selected on the basis of both cumulative (+/- 10 mg/m2) and peak doxorubicin dose (60 or 20 mg/m2, control group 1), or peak dose alone (20 mg/m2, control group 2).
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).
Less severe cardiac changes were seen in patients given PL-DOX relative to historical control patients given comparable cumulative doses of doxorubicin.
在临床前模型中已表明，聚乙二醇化脂质体阿霉素（PL-DOX）比非脂质体阿霉素诱导的心脏毒性更小。心内膜心肌活检是检测蒽环类药物所致心脏损伤的一种高度敏感且特异的方法。
对10例接受累积剂量为440 - 840mg/m²的PL-DOX（每两周20mg/m²）的卡波西肉瘤患者的心肌组织进行评估，以寻找蒽环类药物所致心脏损伤的证据。对照组选自之前两项心脏活检方案中接受累积阿霉素剂量为174 - 671mg/m²的患者。根据累积剂量（±10mg/m²）和阿霉素峰值剂量（60或20mg/m²，对照组1）或仅根据峰值剂量（20mg/m²，对照组2）选择两个对照组。
尽管PL-DOX患者的蒽环类药物累积剂量更高，但与阿霉素对照组相比，其活检评分显著更低。对于第1组，PL-DOX组和阿霉素组的活检评分中位数分别为0.3和3.0（P = 0.002， Cochr an - Mantel - Haenszel行平均差异检验）；对于第2组，分别为1.25（P < 0.001，Wilcoxon秩和检验）。
与接受相当累积剂量阿霉素的历史对照患者相比，接受PL-DOX的患者心脏变化较轻。
