Department of Medicine, Division of Hematology/Oncology, Mount Sinai Beth Israel, 16th Street and 1st Avenue, New York, NY 10003, USA.
Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA; School of Public Health, The University of Texas Health Science Center at Houston, 1200 Herman-Pressler Street, Houston, TX 77030, USA.
Eur J Cancer. 2015 Nov;51(16):2314-20. doi: 10.1016/j.ejca.2015.07.031. Epub 2015 Sep 3.
Anthracyclines play a broad and important role in the care of patients with either operable or metastatic breast cancer. However cardiotoxicity narrows the therapeutic index of this drug class leading to potentially clinically meaningful treatment delays or discontinuations. We conducted a Bayesian network meta-analysis, a validated statistical methodology, allowing direct and indirect comparison of cardiotoxicity of different anthracycline and non-anthracycline regimens.
We conducted a systematic review of prospective randomised controlled trials through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Google Scholar comparing non-anthracycline based regimens (NON), doxorubicin (DOX), epirubicin (EPI) and liposomal doxorubicin (LD). We included studies published up to 1st January 2014 in both adjuvant and metastatic contexts. Notably, HER2/neu-targeted regimens were excluded. We assessed the studies' eligibility criteria and data collection with consensus of two independent authors. Our primary outcome measure was cardiac events grade 3 or greater (CE3) in accordance with Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. A Bayesian pairwise and network meta-analysis was conducted to estimate pooled Odds Ratio (OR).
Nineteen randomised controlled trials met eligibility criteria and were included in this analysis. We found a trend showing that LD is less cardiotoxic than DOX with an OR of 0.60 (95% confidence interval (CI) 0.34-1.07) There was no difference between Epi and LD with an OR of 0.95 (95%CI 0.39-2.33). DOX is more cardiotoxic than Non with an OR of 1.57 (95%CI 0.90-2.72).
DOX has higher CE3 rates than NON does. LD statistically trended to lower cardiac event rates than DOX. Non-statistical significance among EPI, LD and DOX with regard to cardiac toxicity indicates that avoidance of CE3 should not motivate selection of a particular anthracycline in otherwise healthy women in whom total lifetime anthracycline exposure will likely be limited. Overall low incidence of CE3 with any type of anthracycline indicates that we can safely use any anthracycline if cumulative dose limits are not exceeded. While CE3 does not limit our choice of anthracycline LD appears to be the least cardiotoxic.
Takeo Fujii is supported by the grant named Young Investigator Award for Study Abroad in Clinical Epidemiology from St. Luke's Life Science Institution.
蒽环类药物在可手术或转移性乳腺癌患者的治疗中具有广泛而重要的作用。然而，心脏毒性缩小了此类药物的治疗指数，导致潜在的临床意义上的治疗延迟或中断。我们进行了贝叶斯网络荟萃分析，这是一种经过验证的统计方法，允许直接和间接比较不同蒽环类药物和非蒽环类药物方案的心脏毒性。
我们通过 MEDLINE、EMBASE、Cochrane 对照试验中心注册库和 Google Scholar 进行了一项系统综述，比较了非蒽环类药物方案（NON）、多柔比星（DOX）、表柔比星（EPI）和脂质体多柔比星（LD）。我们纳入了截至 2014 年 1 月 1 日在辅助和转移性环境中发表的前瞻性随机对照试验。值得注意的是，排除了曲妥珠单抗靶向治疗方案。我们通过两名独立作者的共识评估了研究的纳入标准和数据收集。我们的主要结局指标是根据不良事件常用术语标准（CTCAE）第 4.0 版评定的 3 级或更高级别的心脏事件（CE3）。采用贝叶斯成对和网络荟萃分析来估计合并优势比（OR）。
19 项符合纳入标准的随机对照试验被纳入本分析。我们发现 LD 比 DOX 心脏毒性更小的趋势，OR 为 0.60（95%置信区间[CI]为 0.34-1.07）。EPI 和 LD 之间没有差异，OR 为 0.95（95%CI 为 0.39-2.33）。DOX 比 NON 更具心脏毒性，OR 为 1.57（95%CI 为 0.90-2.72）。
DOX 的 CE3 发生率高于 NON。LD 统计学上倾向于比 DOX 更低的心脏事件发生率。EPI、LD 和 DOX 之间关于心脏毒性的非统计学显著性表明，在总终生蒽环类药物暴露量可能有限的健康女性中，避免 CE3 不应促使选择特定的蒽环类药物。任何类型的蒽环类药物的 CE3 发生率都很低，这表明只要不超过累积剂量限制，我们就可以安全使用任何蒽环类药物。虽然 CE3 不会限制我们对蒽环类药物的选择，但 LD 似乎是心脏毒性最小的。
Takeo Fujii 得到了 St. Luke's Life Science Institution 颁发的临床流行病学出国留学青年研究员奖的资助。
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