van Dalen Elvira C, van der Pal Helena J H, Caron Huib N, Kremer Leontien Cm
Paediatric Oncology, Emma Children's Hospital / Academic Medical Center, PO Box 22660 (room F8-257), Amsterdam, Netherlands, 1100 DD.
Cochrane Database Syst Rev. 2009 Oct 7(4):CD005008. doi: 10.1002/14651858.CD005008.pub3.
The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. To prevent this cardiotoxicity, different anthracycline dosage schedules have been studied.
To determine the occurrence of cardiotoxicity with the use of different anthracycline dosage schedules (i.e. peak doses and infusion durations) in cancer patients.
We searched the databases of The Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2008), MEDLINE (1966 to November 2008) and EMBASE (1980 to November 2008). Also, we searched reference lists of relevant articles, conference proceedings and ongoing trials databases.
Randomised controlled trials (RCTs) in which different anthracycline dosage schedules were compared in cancer patients (children and adults).
Two authors independently performed the study selection, the risk of bias assessment and the data-extraction.
We identified seven RCTs addressing different anthracycline infusion durations. The meta-analysis showed a statistically significant lower rate of clinical heart failure with an infusion duration of 6 hours or longer as compared to a shorter infusion duration (relative risk (RR) = 0.27; 95% confidence interval (CI) 0.09 to 0.81; 5 studies; 557 patients). The majority of patients included in these studies were adults with different solid tumours. For different anthracycline peak doses we identified two RCTs addressing a doxorubicin peak dose of less than 60 mg/m(2) versus 60 mg/m(2) or more, one RCT addressing a liposomal doxorubicin peak dose of 25 mg/m(2) versus 50 mg/m(2) and one RCT addressing an epirubicin peak dose of 83 mg/m(2) versus 110 mg/m(2). In none of the studies a significant difference in the occurrence of clinical heart failure was identified. All patients included in these studies were adults with different solid tumours.
AUTHORS' CONCLUSIONS: An anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure and it seems to reduce the risk of subclinical cardiac damage. Since there is only a small amount of data for children and data obtained in adults cannot be extrapolated to children, different anthracycline infusion durations should be evaluated further in children.No significant difference in the occurrence of clinical heart failure was identified in patients treated with a doxorubicin peak dose of less than 60 mg/m(2) or 60 mg/m(2) or more. For the other identified peak doses only one RCT was available, so no definitive conclusions can be made about the occurrence of cardiotoxicity. More high quality research is needed, both in children and adults and in leukaemias and solid tumours.
蒽环类化疗药物的使用因心脏毒性的发生而受到限制。为预防这种心脏毒性，人们研究了不同的蒽环类药物给药方案。
确定癌症患者使用不同蒽环类药物给药方案（即峰值剂量和输注持续时间）时心脏毒性的发生情况。
我们检索了Cochrane对照试验注册库（CENTRAL）（Cochrane图书馆，2008年第4期）、MEDLINE（1966年至2008年11月）和EMBASE（1980年至2008年11月）的数据库。此外，我们还检索了相关文章的参考文献列表、会议论文集和正在进行的试验数据库。
在癌症患者（儿童和成人）中比较不同蒽环类药物给药方案的随机对照试验（RCT）。
两位作者独立进行研究筛选、偏倚风险评估和数据提取。
我们确定了7项针对不同蒽环类药物输注持续时间的RCT。荟萃分析显示，与较短的输注持续时间相比，输注持续时间为6小时或更长时，临床心力衰竭的发生率在统计学上显著降低（相对风险（RR）=0.27；95%置信区间（CI）0.09至0.81；5项研究；557例患者）。这些研究中的大多数患者为患有不同实体瘤的成人。对于不同的蒽环类药物峰值剂量，我们确定了2项RCT，比较了阿霉素峰值剂量小于60mg/m²与60mg/m²或更高的情况，1项RCT比较了脂质体阿霉素峰值剂量25mg/m²与50mg/m²的情况，以及1项RCT比较了表柔比星峰值剂量83mg/m²与110mg/m²的情况。在这些研究中，均未发现临床心力衰竭发生率存在显著差异。这些研究中的所有患者均为患有不同实体瘤的成人。
蒽环类药物输注持续时间为6小时或更长可降低临床心力衰竭的风险，似乎也可降低亚临床心脏损伤的风险。由于儿童的数据很少，且成人获得的数据不能外推至儿童，因此应在儿童中进一步评估不同的蒽环类药物输注持续时间。阿霉素峰值剂量小于60mg/m²或60mg/m²或更高的患者，临床心力衰竭发生率无显著差异。对于其他确定的峰值剂量，仅有1项RCT，因此关于心脏毒性的发生无法得出明确结论。儿童和成人以及白血病和实体瘤都需要更多高质量的研究。
