van Dalen E C, van der Pal H J H, Caron H N, Kremer L C M
Emma Children's Hospital/Academic Medical Center, Pediatrics, Meibergdreef 9, PO Box 22660, 1100 DD Amsterdam, Netherlands.
Cochrane Database Syst Rev. 2006 Oct 18(4):CD005008. doi: 10.1002/14651858.CD005008.pub2.
The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline dosage schedules (i.e. peak doses and infusion durations) have been studied.
The primary objective was to determine the occurrence of cardiotoxicity with the use of different anthracycline dosage schedules in cancer patients.
We searched the databases of The Cochrane Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to June 2004) and EMBASE (1980 to June 2004). In addition, 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, quality assessment and data-extraction including adverse effects.
We identified six RCTs of varying quality addressing different anthracycline infusion durations (625 patients). 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, i.e. maximal duration of 1 hour (RR = 0.27; 95% confidence interval (CI) 0.09 to 0.81; 5 studies; 557 patients). In individual studies the infusion duration of 6 hours or longer also seemed to reduce the risk of subclinical cardiac damage. No statistically significant difference in response rate was found (RR = 0.83; 95% CI 0.45 to 1.54; 2 studies; 292 patients). No statistically significant difference in overall survival was found (HR = 1,42; 95% CI 0.61 to 3.30; 2 studies; 322 patients), but there was unexplained heterogeneity (I(2)=75%). No conclusions can be made regarding adverse effects. It should be emphasised that the majority of patients included in these studies were adults with different solid tumours. Children with leukaemia could not be included in the performed meta-analyses, but they were included in the descriptive results of non-pooled studies. No RCTs addressing different anthracycline peak doses with the same cumulative anthracycline dose in both treatment groups were identified.
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. There is no evidence which suggests a difference in response rate and survival between both treatment groups. Since there is only a small amount of data for children and also because data obtained in adults cannot be extrapolated to children, different anthracycline infusion durations should be evaluated further in children. For different anthracycline peak doses no high quality evidence was available and therefore, no definitive conclusions can be made about the occurrence of cardiotoxicity in patients treated with different anthracycline peak doses.
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，人们对不同的蒽环类药物给药方案（即峰值剂量和输注持续时间）进行了研究。
主要目的是确定癌症患者使用不同蒽环类药物给药方案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》2004年第2期）、MEDLINE（1966年至2004年6月）和EMBASE（1980年至2004年6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选择、质量评估和数据提取，包括不良反应。
我们确定了6项质量各异的RCT，涉及不同的蒽环类药物输注持续时间（625例患者）。荟萃分析显示，与较短的输注持续时间（即最长1小时）相比，输注持续时间为6小时或更长时间时，临床心力衰竭的发生率在统计学上显著降低（RR = 0.27；95%置信区间（CI）0.09至0.81；5项研究；557例患者）。在个别研究中，6小时或更长时间的输注持续时间似乎也降低了亚临床心脏损伤的风险。未发现缓解率有统计学显著差异（RR = 0.83；95% CI 0.45至1.54；2项研究；292例患者）。未发现总生存率有统计学显著差异（HR = 1.42；95% CI 0.61至3.30；2项研究；322例患者），但存在无法解释的异质性（I² = 75%）。关于不良反应无法得出结论。应强调的是，这些研究纳入的大多数患者是患有不同实体瘤的成年人。患有白血病的儿童无法纳入所进行的荟萃分析，但纳入了非汇总研究的描述性结果中。未发现两个治疗组蒽环类药物累积剂量相同但峰值剂量不同的RCT。
蒽环类药物输注持续时间为6小时或更长时间可降低临床心力衰竭的风险，且似乎可降低亚临床心脏损伤的风险。没有证据表明两个治疗组在缓解率和生存率方面存在差异。由于儿童的数据较少，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。对于不同的蒽环类药物峰值剂量，没有高质量的证据，因此，对于接受不同蒽环类药物峰值剂量治疗的患者心脏毒性的发生情况无法得出明确结论。
