Subacute cardiotoxicity caused by anthracycline therapy in children:: can dexrazoxane prevent this effect?
Subacute cardiotoxicity caused by anthracycline therapy in children:: can dexrazoxane prevent this effect?
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DOI：
10.1007/s00431-006-0370-2
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发表时间：
2007-11-01
影响因子：
3.6
通讯作者：
Mueller, Judit
中科院分区：
文献类型：
--
作者：
Kovacs, Gabor T.;Erlaky, Hajna;Mueller, Judit
本文对1991年至2003年间诊断为骨肉瘤、尤文氏肉瘤、软组织肉瘤和白血病的108例患者进行了研究。其中，41名儿童（1996年开始治疗）从治疗开始就接受右拉唑烷（D组）作为化疗（平均随访时间：8.2±3.9年）。右旋唑烷的剂量比蒽环类药物剂量高20倍，并作为20分钟乳酸钠输注给药。对照组（C组）包括67名儿童（均在1996年之前接受治疗），未接受任何心脏保护（平均随访时间：12.3±3.2年）。C组和D组均短时间输注蒽环类药物（1 ~ 3 h）。两组间蒽环类药物的累积剂量没有差异（表1）。在调查期间，支持性治疗没有改变。定期行心脏超声检查，测定左心室功能分数缩短（FS）。急性心脏毒性发生率C组为13.4%，D组为7.3%，差异无统计学意义。治疗2年后，13.7%的C组患者和0%的D组患者的心功能（以FS表示）异常低（< 30%）（p= 0.034）（图2）。C组19.3%的患者和D组0%的患者治疗3年后仍异常低（p= 0.008）（图2）。1 b)。在5年随访中，14.9%的C组患者FS低于30%，2.4%的D组患者FS低于30%（图1c）。C组7例充血性心力衰竭患者需要心脏保护药物（洋地黄、速尿、血管紧张素转换酶抑制剂）治疗至少6个月。D组仅有1例患者接受心脏药物治疗。扩张性心肌病是蒽环类药物治疗的严重并发症，即使在儿童中，较低的累积剂量（< 300 mg/m2）也可能导致不可逆的充血性心力衰竭。据报道，轻微心脏毒性的发生率在12%至32%之间，死亡率或严重功能障碍的发生率在2%至7%之间
A total of 108 patients with the diagnosis of osteosarcoma, Ewing-sarcoma, soft tissue sarcoma and leukemia were studied between 1991 and 2003. Of these, 41 children (treated from 1996) received dexrazoxane (Group D) as chemotherapy from the beginning of their treatment (mean follow-up: 8.2±3.9 years). The dose of dexrazoxane was 20-fold higher than the anthracycline dose and was administered as a 20-min sodium-lactate infusion. The control (Group C) cohort comprised 67 children (all treated before 1996) who did not receive any cardioprotection (mean follow-up: 12.3±3.2 years). All patients in the C and D groups received anthracyclines in the form of short infusions (1–3 h). The cumulative dose of anthracycline did not differ between the two groups (Table 1). Supportive treatment did not change during the investigated period. Cardiac ultrasound examinations were performed regularly, and fractional shortening (FS) for detecting left ventricular function was measured.The incidence of acute cardiotoxicity was 13.4% in Group C patients and 7.3% in Group D patients, a nonsignificant difference. Cardiac function, expressed as FS, was abnormally low (< 30%) 2 years after therapy in 13.7% of the Group C patients and in 0% of the Group D patients (p= 0.034)(Fig. 1 a) and was still abnormally low 3 years after therapy in 19.3% of the Group C patients and 0% of the Group D patients (p= 0.008)(Fig. 1 b). At the 5-year follow-up, FS was under 30% in 14.9% of the Group C patients and 2.4% of the Group D patients (Fig. 1 c). Seven patients in Group C needed heart-protective drugs (digitalis, furosemide, angiotensine converting enzyme inhibitors) for congestive heart failure for at least 6 months. Only one patient in Group D received cardiac drugs. Dilatative cardiomyopathy is a severe complication of anthracycline therapy, and even in children, lower cumulative doses (< 300 mg/m2) may cause irreversible congestive heart failure [3]. The incidence of slight cardiotoxicity has been reported to vary between 12 and 32% and mortality or severe dysfunction to vary between 2 and 7%, depending