辅助治疗切除的胰腺腺癌：系统评价和网络荟萃分析。

Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis.

机构信息

Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.

Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.

出版信息

Lancet Oncol. 2013 Oct;14(11):1095-1103. doi: 10.1016/S1470-2045(13)70388-7. Epub 2013 Sep 12.

DOI:10.1016/S1470-2045(13)70388-7

PMID:24035532

Abstract

BACKGROUND

Major adjuvant treatments for pancreatic adenocarcinoma include fluorouracil, gemcitabine, chemoradiation, and chemoradiation plus fluorouracil or gemcitabine. Since the optimum regimen remains inconclusive, we aimed to compare these treatments in terms of overall survival after tumour resection and in terms of grade 3-4 toxic effects with a systematic review and random-effects Bayesian network meta-analysis.

METHODS

We searched PubMed, trial registries, and related reviews and abstracts for randomised controlled trials comparing the above five treatments with each other or observation alone before April 30, 2013. We estimated relative hazard ratios (HRs) for death and relative odds ratios (ORs) for toxic effects among different therapies by combining HRs for death and survival durations and ORs for toxic effects of included trials. We assessed the effects of prognostic factors on survival benefits of adjuvant therapies with meta-regression.

FINDINGS

Ten eligible articles reporting nine trials were included. Compared with observation, the HRs for death were 0·62 (95% credible interval 0·42-0·88) for fluorouracil, 0·68 (0·44-1·07) for gemcitabine, 0·91 (0·55-1·46) for chemoradiation, 0·54 (0·15-1·80) for chemoradiation plus fluorouracil, and 0·44 (0·10-1·81) for chemoradiation plus gemcitabine. The proportion of patients with positive lymph nodes was inversely associated with the survival benefit of adjuvant treatments. After adjustment for this factor, fluorouracil (HR 0·65, 0·49-0·84) and gemcitabine (0·59, 0·41-0·83) improved survival compared with observation, whereas chemoradiation resulted in worse survival than fluorouracil (1·69, 1·12-2·54) or gemcitabine (1·86, 1·04-3·23). Chemoradiation plus gemcitabine was ranked the most toxic, with significantly higher haematological toxic effects than second-ranked chemoradiation plus fluorouracil (OR 13·33, 1·01-169·36).

INTERPRETATION

Chemotherapy with fluorouracil or gemcitabine is the optimum adjuvant treatment for pancreatic adenocarcinoma and reduces mortality after surgery by about a third. Chemoradiation plus chemotherapy is less effective in prolonging survival and is more toxic than chemotherapy.

FUNDING

None.

摘要

背景

胰腺癌的主要辅助治疗方法包括氟尿嘧啶、吉西他滨、放化疗以及氟尿嘧啶或吉西他滨联合放化疗。由于最佳方案尚未确定，我们旨在通过系统评价和随机效应贝叶斯网络荟萃分析，比较这些治疗方法在肿瘤切除后的总体生存率和 3-4 级毒性方面的差异。

方法

我们检索了 PubMed、试验注册处以及相关的综述和摘要，以查找比较上述五种治疗方法相互之间以及与单独观察的随机对照试验，检索时间截至 2013 年 4 月 30 日。我们通过组合包含试验的死亡率和生存时间的相对危险比（HR）以及毒性的相对比值比（OR），来估计不同治疗方法的死亡相对 HR 和毒性相对 OR。我们通过荟萃回归来评估预后因素对辅助治疗生存获益的影响。

结果

纳入了 10 项符合条件的文章，报道了 9 项试验。与单独观察相比，氟尿嘧啶的死亡 HR 为 0.62（95%可信区间 0.42-0.88），吉西他滨为 0.68（0.44-1.07），放化疗为 0.91（0.55-1.46），放化疗联合氟尿嘧啶为 0.54（0.15-1.80），放化疗联合吉西他滨为 0.44（0.10-1.81）。阳性淋巴结患者的比例与辅助治疗的生存获益呈负相关。在调整了这一因素后，氟尿嘧啶（HR 0.65，0.49-0.84）和吉西他滨（0.59，0.41-0.83）与单独观察相比可改善生存，而放化疗的生存获益不如氟尿嘧啶（1.69，1.12-2.54）或吉西他滨（1.86，1.04-3.23）。放化疗联合吉西他滨的毒性最大，与排名第二的放化疗联合氟尿嘧啶相比，血液学毒性显著更高（OR 13.33，1.01-169.36）。