Broeyer Frederik J F, Osanto Susanne, Suzuki Jun, de Jongh Felix, van Slooten Henk, Tanis Bea C, Bruning Tobias, Bax Jeroen J, Ritsema van Eck Henk J, de Kam Marieke L, Cohen Adam F, Mituzhima Yutaka, Burggraaf Jacobus
Centre for Human Drug Research, Leiden, The Netherlands.
Br J Clin Pharmacol. 2014 Nov;78(5):950-60. doi: 10.1111/bcp.12429.
Anthracycline-induced cardiotoxicity is (partly) mediated by free radical overload. A randomized study was performed in breast cancer patients to investigate whether free radical scavenger super oxide dismutase (SOD) protects against anthracycline-induced cardiotoxicity as measured by changes in echo, electrocardiography and an array of biomarkers.
Eighty female, chemotherapy-naïve breast cancer patients (median age 49, range 24-67 years) scheduled for four or five courses of adjuvant 3 weekly doxorubicin plus cyclophosphamide (AC) chemotherapy, were randomly assigned to receive 80 mg PC-SOD (human recombinant SOD bound to lecithin) or placebo, administered intravenously (i.v.) immediately prior to each AC course. The primary end point was protection against cardiac damage evaluated using echocardiography, QT assessments and a set of biochemical markers for myocardial function, oxidative stress and inflammation. Assessments were performed before and during each course of chemotherapy, and at 1, 4 and 9 months after completion of the chemotherapy regimen. In all patients cardiac effects such as increases in NT-proBNP concentration and prolongation of the QTc interval were noticed. There were no differences between the PC-SOD and placebo-treated patients in systolic or diastolic cardiac function or for any other of the biomarkers used to assess the cardiac effects of anthracyclines.
PC-SOD at a dose of 80 mg i.v. is not cardioprotective in patients with breast carcinoma treated with anthracyclines.
蒽环类药物引起的心脏毒性(部分)是由自由基过载介导的。在乳腺癌患者中进行了一项随机研究,以调查自由基清除剂超氧化物歧化酶(SOD)是否能预防蒽环类药物引起的心脏毒性,这通过超声心动图、心电图的变化以及一系列生物标志物来衡量。
八十名初治的女性乳腺癌患者(中位年龄49岁,范围24 - 67岁)计划接受三周一疗程,共四或五个疗程的阿霉素联合环磷酰胺(AC)辅助化疗,被随机分配接受80毫克的聚乙二醇化超氧化物歧化酶(与卵磷脂结合的重组人SOD)或安慰剂,在每次AC疗程前立即静脉注射。主要终点是通过超声心动图、QT评估以及一组用于评估心肌功能、氧化应激和炎症的生化标志物来评估对心脏损伤的预防作用。在化疗的每个疗程之前和期间,以及化疗方案完成后的1、4和9个月进行评估。在所有患者中均观察到心脏效应,如NT - proBNP浓度升高和QTc间期延长。在收缩或舒张心脏功能方面,以及用于评估蒽环类药物心脏效应的任何其他生物标志物方面,聚乙二醇化超氧化物歧化酶治疗组和安慰剂治疗组之间没有差异。
对于接受蒽环类药物治疗的乳腺癌患者,静脉注射80毫克的聚乙二醇化超氧化物歧化酶没有心脏保护作用。