Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: A meta-analysis of randomised trials
Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: A meta-analysis of randomised trials
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DOI：
10.1016/j.ejca.2012.08.019
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发表时间：
2013-02-01
影响因子：
8.4
通讯作者：
Tagliaferri, Pierosandro
中科院分区：
文献类型：
--
作者：
Ciliberto, Domenico;Botta, Cirino;Tagliaferri, Pierosandro
背景：胰腺癌是全球癌症相关死亡的第四大原因。吉西他滨是晚期疾病的主要治疗方法。然而，几乎所有评估吉西他滨联合治疗方案益处的最新试验均未能证明总生存期 (OS) 有所改善。在这项研究中，我们对随机临床试验 (RCT) 进行了系统回顾和荟萃分析，以研究基于吉西他滨的联合方案与单用吉西他滨治疗胰腺癌的疗效和安全性相比。方法：通过搜索不同的数据库（PubMed、Embase 和 Cochrane 图书馆对照试验中央登记处）和主要癌症会议的摘要来收集临床试验。我们考虑的时期为 1997 年 1 月至 2012 年 1 月。主要终点是 OS，次要终点是缓解率 (RR)、疾病控制率 (DCR) 和安全性。提取 OS 的风险比 (HR)、RR、DCR 的比值比 (OR) 和 3-4 级毒性率 (TR) 的风险比，并用于统计分析。使用随机效应模型得出荟萃分析估计值。结果：选择了涉及总共 10,660 名患者的 34 项试验并将其纳入最终分析。分析显示，联合化疗可带来 OS 方面的益处（HR：0.93；95% 置信区间 (CI)：0.89-0.97；p = 0.001）。 RR 和 DCR 的 OR 均显示联合治疗具有显着优势（RR 的 OR：0.60，95% CI：0.47-0.76，p < 0.001；DCR 的 OR：0.79；95% CI：0.66-0.93；p = 0.006）。联合治疗的毒性更频繁，腹泻（0.53，95% CI：0.36-0.79）、恶心（0.74，95% CI：0.56-0.96）、中性粒细胞减少（0.71，95% CI：0.59-0.85）和血小板减少（0.57，95% CI：0.57，95% CI：0.59-0.85）的风险比具有显着性。 0.43-0.75).解释：与单独吉西他滨相比，联合化疗显着改善晚期胰腺癌（APC）的 OS。然而，这种优势是微乎其微的，而与治疗相关的毒性却增加了，这表明基于吉西他滨的联合方案仅在选定的患者群体中使用。基于转化方法和创新的经过验证的生物标志物的新的前瞻性试验在这一主题上备受期待。 (C) 2012 Elsevier Ltd. 保留所有权利。
Background: Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Gemcitabine is the mainstay treatment for advanced disease. However, almost all up-to-date trials, that evaluated the benefit of gemcitabine-combination schedules, failed to demonstrate an improvement in overall survival (OS). In this study, we performed a systematic review and a meta-analysis of randomised clinical trials (RCTs) to investigate the efficacy and safety of gemcitabine-based combination regimens as compared to gemcitabine alone in the management of pancreatic cancer.Methods: Clinical trials were collected by searching different databases (PubMed, Embase and the Central Registry of Controlled Trials of the Cochrane Library) and abstracts from major cancer meetings. We considered period ranging from January 1997 to January 2012. Primary end-point was OS, secondary end-points were response rate (RR), disease control rate (DCR) and safety. Hazard ratios (HRs) of OS, odds-ratios (ORs) of RR, DCR and risk ratios of grade 3-4 toxicity rates (TRs), were extracted as presented in retrieved studies and used for statistical analysis. Meta-analytic estimates were derived using random-effects model.Findings: Thirty-four trials for a total of 10,660 patients were selected and included in the final analysis. The analysis showed that combination chemotherapy confers benefit in terms of OS (HR: 0.93; 95% confidence interval (CI): 0.89-0.97; p = 0.001). ORs for both RR and DCR demonstrated a significant advantage for combination therapy (OR for RR: 0.60, 95% CI: 0.47-0.76, p < 0.001; OR for DCR: 0.79; 95% CI: 0.66-0.93; p = 0.006). Toxicities were more frequent with the combination treatment and significance in terms of risk ratio was reached for diarrhoea (0.53, 95% CI: 0.36-0.79), nausea (0.74, 95% CI: 0.56-0.96), neutropenia (0.71, 95% CI: 0.59-0.85) and thrombocytopenia (0.57, 95% CI: 0.43-0.75).Interpretation: The combination chemotherapy as compared to gemcitabine alone significantly improves OS in advanced pancreatic cancer (APC). However, this advantage is marginal whereas the treatment-related toxicity is increased, suggesting the use of gemcitabine-based combination regimens only in selected patient populations. New prospective trials, based on translational approaches and innovative validated biomarkers, are eagerly awaited on this topic. (C) 2012 Elsevier Ltd. All rights reserved.