背景:蒽环类化疗相关的心脏毒性限制了其在已有心肌病或心力衰竭患者中的应用。Dexrazoxane可以防止蒽环类药物的心脏毒性作用,但是在美国和一些欧洲国家,其使用仅限于累积剂量>300mg/m2的阿霉素(蒽环类药物)的晚期乳腺癌成人.我们评估了在患有心肌病的成年患者中使用右雷佐生作为心脏保护剂的标签外使用,正在接受蒽环类药物化疗.
方法:2015年7月至2017年6月,连续5名患者,与预先存在的,无症状,需要蒽环类化疗的收缩期左心室(LV)功能障碍,同时用标签外的右雷佐辛处理,每次蒽环类药物剂量前30分钟给药,无论癌症类型或阶段。人口统计,心血管,与癌症相关的结局进行了比较,并与在同一家医院早期接受无症状心肌病治疗的3例连续患者的结局进行了比较.
结果:五名接受右雷佐生治疗的患者和三名没有接受右雷佐生治疗的患者的平均年龄分别为70.6和72.6岁,分别。所有五名接受右雷佐生治疗的患者都成功完成了计划的化疗(阿霉素,280到300mg/m2)。用右雷佐生治疗,左心室收缩功能变化最小,化疗后平均左心室射血分数(LVEF)从基线时的39%降至34%.右雷佐生治疗的患者均未出现症状性心力衰竭或生物标志物升高(心肌肌钙蛋白I或脑利钠肽)。在没有右旋雷佐生治疗的三名患者中,两人接受了阿霉素(平均剂量,210mg/m2),一个接受柔红霉素(540mg/m2)。蒽环类药物治疗导致LVEF从基线时的42.5%显著降低至18%。这三人都出现了症状性心力衰竭,需要住院治疗和静脉利尿剂治疗。其中2人死于心源性休克和多器官衰竭。
结论:在先前存在的心肌病患者中同时给予右雷佐生可以成功地提供以蒽环类为基础的化疗,而没有心脏代偿失调。有必要进行更大的前瞻性试验,以检查右雷佐生在需要蒽环类药物的先前存在的心肌病患者中作为心脏保护剂的使用。
BACKGROUND: Cardiotoxicity associated with anthracycline-based chemotherapies has limited their use in patients with preexisting cardiomyopathy or heart failure. Dexrazoxane protects against the cardiotoxic effects of anthracyclines, but in the USA and some European countries, its use had been restricted to adults with advanced breast cancer receiving a cumulative doxorubicin (an anthracycline) dose > 300 mg/m2. We evaluated the off-label use of dexrazoxane as a cardioprotectant in adult patients with preexisting cardiomyopathy, undergoing anthracycline chemotherapy.
METHODS: Between July 2015 and June 2017, five consecutive patients, with preexisting, asymptomatic, systolic left ventricular (LV) dysfunction who required anthracycline-based chemotherapy, were concomitantly treated with off-label dexrazoxane, administered 30 min before each anthracycline dose, regardless of cancer type or stage. Demographic, cardiovascular, and cancer-related outcomes were compared to those of three consecutive patients with asymptomatic cardiomyopathy treated earlier at the same hospital without dexrazoxane.
RESULTS: Mean age of the five dexrazoxane-treated patients and three patients treated without dexrazoxane was 70.6 and 72.6 years, respectively. All five dexrazoxane-treated patients successfully completed their planned chemotherapy (doxorubicin, 280 to 300 mg/m2). With dexrazoxane therapy, changes in LV systolic function were minimal with mean left ventricular ejection fraction (LVEF) decreasing from 39% at baseline to 34% after chemotherapy. None of the dexrazoxane-treated patients experienced symptomatic heart failure or elevated biomarkers (cardiac troponin I or brain natriuretic peptide). Of the three patients treated without dexrazoxane, two received doxorubicin (mean dose, 210 mg/m2), and one received daunorubicin (540 mg/m2). Anthracycline therapy resulted in a marked reduction in LVEF from 42.5% at baseline to 18%. All three developed symptomatic heart failure requiring hospitalization and intravenous diuretic therapy. Two of them died from cardiogenic shock and multi-organ failure.
CONCLUSIONS: The concomitant administration of dexrazoxane in patients with preexisting cardiomyopathy permitted successful delivery of anthracycline-based chemotherapy without cardiac decompensation. Larger prospective trials are warranted to examine the use of dexrazoxane as a cardioprotectant in patients with preexisting cardiomyopathy who require anthracyclines.