Ghersi Davina, Willson Melina L, Chan Matthew Ming Ki, Simes John, Donoghue Emma, Wilcken Nicholas
Research Translation Group, National Health and Medical Research Council, 16 Marcus Clarke Street, Canberra, ACT, Australia, 2601.
Cochrane Database Syst Rev. 2015 Jun 10;2015(6):CD003366. doi: 10.1002/14651858.CD003366.pub3.
It is generally accepted that taxanes are among the most active chemotherapy agents in the management of metastatic breast cancer. This is an update of a Cochrane review first published in 2003.
The objective of this review was to compare taxane-containing chemotherapy regimens with regimens not containing a taxane in the management of women with metastatic breast cancer.
In this review update, we searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov on 14 February 2013 using keywords such as 'advanced breast cancer' and 'chemotherapy'. We searched reference lists of articles, contacted study authors, and did not apply any language restrictions.
Randomised controlled trials comparing taxane-containing chemotherapy regimens to regimens without taxanes in women with metastatic breast cancer. We included published and unpublished studies.
Two review authors independently assessed trial quality and extracted data. We derived hazard ratios (HRs) for overall survival, time to progression, and time to treatment failure where possible, and used a fixed-effect model for meta-analysis. We represented objective tumour response rates and toxicity as risk ratios (RRs). We extracted quality of life data where present.
This review included 28 studies. The updated analysis included 6871 randomised women, while the original review had 3643 women. Of the 28 included studies, we considered 19 studies to be at low risk of bias overall; however, some studies failed to report details on allocation concealment and methods of outcome assessment for those outcomes that are more likely to be influenced by a lack of blinding (for example tumour response rate). Studies varied in the taxane-containing chemotherapy backbone, and the comparator arms and were categorised into three groups: Regimen A plus taxane versus Regimen A (2 studies); Regimen A plus taxane versus Regimen B (14 studies); and single-agent taxane versus Regimen C (13 studies). Thirteen studies used paclitaxel, 14 studies used docetaxel, and 1 study allowed the investigator to decide on the type of taxane; the majority of studies delivered a taxane every 3 weeks. Twenty studies administered taxanes as first-line treatment, and 21 studies involved anthracycline naïve women in the metastatic setting. The combined HR for overall survival and time to progression favoured the taxane-containing regimens (HR 0.93, 95% confidence interval (CI) 0.88 to 0.99, P = 0.002, deaths = 4477; and HR 0.92, 95% CI 0.87 to 0.97, P = 0.002, estimated 5122 events, respectively) with moderate to substantial heterogeneity across trials. If the analyses were restricted to studies of first-line chemotherapy, this effect persisted for overall survival (HR 0.93, 95% CI 0.87 to 0.99, P = 0.03) but not for time to progression (HR 0.96, 95% CI 0.90 to 1.02, P = 0.22). Tumour response rates appeared to be better with taxane-containing chemotherapy in assessable women (RR 1.20, 95% CI 1.14 to 1.27, P < 0.00001) with substantial heterogeneity across studies. Taxanes were associated with an increased risk of neurotoxicity (RR 4.84, 95% CI 3.18 to 7.35, P < 0.00001, 24 studies) and hair loss (RR 2.37, 95% CI 1.45 to 3.87, P = 0.0006, 11 studies) but less nausea/vomiting compared to non-taxane-containing regimens (RR 0.62, 95% CI 0.46 to 0.83, P = 0.001, 26 studies). Leukopaenia and treatment-related death did not differ between the two groups (RR 1.07, 95% CI 0.97 to 1.17, P = 0.16, 28 studies; and RR 1.00, 95% CI 0.63 to 1.57, P = 0.99, 23 studies, respectively). For quality of life measures, none of the individual studies reported a difference in overall or any of quality of life subscales between taxane-containing and non-taxane chemotherapy regimens.
AUTHORS' CONCLUSIONS: Taxane-containing regimens appear to improve overall survival, time to progression, and tumour response rate in women with metastatic breast cancer. Taxanes are also associated with an increased risk of neurotoxicity but less nausea and vomiting compared to non-taxane-containing regimens. The considerable heterogeneity encountered across studies probably reflects the varying efficacy of the comparator regimens used in these studies and indicates that taxane-containing regimens are more effective than some, but not all, non-taxane-containing regimens.
一般认为紫杉烷类是转移性乳腺癌治疗中最有效的化疗药物之一。这是对2003年首次发表的Cochrane系统评价的更新。
本系统评价的目的是比较含紫杉烷类的化疗方案与不含紫杉烷类的方案在转移性乳腺癌女性患者治疗中的效果。
在本次系统评价更新中，我们于2013年2月14日检索了Cochrane乳腺癌专业注册库、MEDLINE、EMBASE、世界卫生组织国际临床试验注册平台（WHO ICTRP）和ClinicalTrials.gov，使用了“晚期乳腺癌”和“化疗”等关键词。我们检索了文章的参考文献列表，联系了研究作者，并且未设置任何语言限制。
比较含紫杉烷类化疗方案与不含紫杉烷类方案治疗转移性乳腺癌女性患者的随机对照试验。我们纳入了已发表和未发表的研究。
两名系统评价作者独立评估试验质量并提取数据。我们尽可能得出总生存、疾病进展时间和治疗失败时间的风险比（HR），并使用固定效应模型进行Meta分析。我们将客观肿瘤缓解率和毒性表示为风险比（RR）。我们提取了存在的生活质量数据。
本系统评价纳入了28项研究。更新后的分析纳入了6871名随机分组的女性，而原始系统评价纳入了3643名女性。在纳入的28项研究中，我们认为19项研究总体偏倚风险较低；然而，一些研究未能报告分配隐藏细节以及那些更可能受缺乏盲法影响的结局（如肿瘤缓解率）的结局评估方法。含紫杉烷类的化疗主干、对照臂各不相同，研究被分为三组：方案A加紫杉烷类对比方案A（2项研究）；方案A加紫杉烷类对比方案B（14项研究）；单药紫杉烷类对比方案C（13项研究）。13项研究使用紫杉醇，14项研究使用多西他赛，1项研究允许研究者决定紫杉烷类的类型；大多数研究每3周给予一次紫杉烷类。20项研究将紫杉烷类作为一线治疗，21项研究纳入了转移性情况下未用过蒽环类药物的女性。总生存和疾病进展时间的合并HR支持含紫杉烷类的方案（HR 0.93，95%置信区间（CI）0.88至0.99，P = 0.002，死亡4477例；HR 0.92，95%CI 0.87至0.97，P = 0.002，分别估计5122例事件），各试验间存在中度至高度异质性。如果分析仅限于一线化疗研究，这种效应在总生存方面持续存在（HR 0.93，95%CI 0.87至0.99，P = 0.03），但在疾病进展时间方面不存在（HR 0.96，95%CI 0.90至1.02，P = 0.22）。在可评估的女性中，含紫杉烷类化疗的肿瘤缓解率似乎更好（RR 1.20，95%CI 1.14至1.27，P < 0.00001），各研究间存在高度异质性。紫杉烷类与神经毒性风险增加相关（RR 4.84，95%CI 3.18至7.35，P < 0.00001，24项研究）和脱发相关（RR 2.37，95%CI 1.45至3.87，P = 0.0006，11项研究），但与不含紫杉烷类的方案相比，恶心/呕吐较少（RR 0.62，95%CI 0.46至0.83，P = 0.001，26项研究）。两组间白细胞减少和治疗相关死亡无差异（RR 1.07，95%CI 0.97至1.17，P = 0.16，28项研究；RR 1.00，95%CI 0.63至1.57，P = 0.99，分别23项研究）。对于生活质量测量，没有任何一项单独研究报告含紫杉烷类和不含紫杉烷类化疗方案在总体生活质量或任何生活质量子量表上存在差异。
含紫杉烷类方案似乎可改善转移性乳腺癌女性患者的总生存、疾病进展时间和肿瘤缓解率。与不含紫杉烷类的方案相比，紫杉烷类还与神经毒性风险增加相关，但恶心和呕吐较少。各研究中存在的显著异质性可能反映了这些研究中所用对照方案的不同疗效，并表明含紫杉烷类方案比一些但并非所有不含紫杉烷类的方案更有效。
