Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
BMC Cancer. 2018 Oct 23;18(1):1034. doi: 10.1186/s12885-018-4948-7.
Pancreatic cancer is a highly malignant tumor with a poor prognosis. Chemotherapy such as gemcitabine is still an important treatment. Gemcitabine (Gem) may prolong survival time and delay the development of recurrent disease after complete resection of pancreatic cancer. Currently, some control studies have been performed between certain drugs and gemcitabine monotherapy after pancreatic cancer surgery, but the outcomes were uncertain. Here, we implemented meta-analysis to compare the efficacy between adjuvant treatments and gemcitabine monotherapy in patients with resected pancreatic cancer.
PubMed, Embase and the Central Registry of Controlled Trials of the Cochrane Library searches were undertaken to identify randomized controlled trials (RCTs). Date of search ranged from January 1997 to December 2017. The meta-analysis included six RCTs. The major endpoints involved overall survival (OS), disease-free survival/progress free survival/relapse-free survival (DFS/PFS/RFS) and grade 3-4 toxicity.
Pooled meta-analytic estimates were derived using random-effects model. Subgroup analysis used fixed-effects model. The outcome showed that there was no difference in OS (hazard ratio (HR), 0.87; 95% CI, 0.70-1.07; P = 0.19) and DFS (HR, 0.85; 95% CI, 0.71-1.02; P = 0.08) between the adjuvant treatments group (fluorouracil+folinic acid, S-1, gemcitabine+capecitabine, gemcitabine+erlotinib and gemcitabine+uracil/tegafur) and Gem monotherapy group. However, the subgroup analysis showed that only S-1 chemotherapy, which is an oral fluoropyrimidine agent containing tegafur, gimeracil and oteracil, was significant in OS (HR, 0.59; 95% CI, 0.46-0.74; P < 0.0001) and DFS (HR, 0.63; 95% CI, 0.52-0.75; P < 0.00001) compared with Gem alone. Toxicity analysis showed there was an increased incidence of grade 3/4 diarrhea (risk ratio (RR), 5.11; 95%CI, 3.24-8.05; P < 0.00001) and decreased incidence of grade 3/4 leucopenia (RR, 0.55; 95%CI, 0.31-0.98; P = 0.04), thrombocytopenia (RR, 0.61; 95%CI, 0.39-0.97; P = 0.04) in adjuvant treatments group. Neutropenia (RR, 0.69; 95%CI, 0.36-1.29; P = 0.24) and fatigue (RR, 1.29; 95%CI, 0.95-1.77; P = 0.11) for patients between the two groups were not significantly different.
In our meta-analysis, a significant survival benefit is only observed in the S-1 regimen, but the results are yet to be determined. Optimal cytotoxicity or targeted drug regimens need further validation in clinical trials in the future.
胰腺癌是一种恶性程度很高的肿瘤，预后不良。吉西他滨等化疗仍是重要的治疗方法。吉西他滨（Gem）可能延长胰腺癌完全切除术后的生存时间并延迟复发性疾病的发展。目前，一些对照研究已经在胰腺癌手术后的某些药物与吉西他滨单药治疗之间进行，但结果不确定。在这里，我们进行了荟萃分析，以比较辅助治疗与吉西他滨单药治疗在接受胰腺切除术的患者中的疗效。
我们对 PubMed、Embase 和 Cochrane 图书馆对照试验中心注册库进行了检索，以确定随机对照试验（RCT）。检索日期范围为 1997 年 1 月至 2017 年 12 月。荟萃分析包括 6 项 RCT。主要终点包括总生存期（OS）、无病生存期/无进展生存期/无复发生存期（DFS/PFS/RFS）和 3-4 级毒性。
使用随机效应模型得出汇总荟萃分析估计值。使用固定效应模型进行亚组分析。结果显示，辅助治疗组（氟尿嘧啶+亚叶酸、S-1、吉西他滨+卡培他滨、吉西他滨+厄洛替尼和吉西他滨+尿嘧啶/替加氟）与吉西他滨单药治疗组之间的 OS（风险比（HR），0.87；95%CI，0.70-1.07；P=0.19）和 DFS（HR，0.85；95%CI，0.71-1.02；P=0.08）之间没有差异。然而，亚组分析显示，只有 S-1 化疗（一种含有替加氟、吉美嘧啶和奥替拉西的口服氟嘧啶药物）在 OS（HR，0.59；95%CI，0.46-0.74；P<0.0001）和 DFS（HR，0.63；95%CI，0.52-0.75；P<0.00001）方面具有显著意义。与单独使用 Gem 相比，毒性分析显示，3/4 级腹泻的发生率增加（风险比（RR），5.11；95%CI，3.24-8.05；P<0.00001），3/4 级白细胞减少症（RR，0.55；95%CI，0.31-0.98；P=0.04）、血小板减少症（RR，0.61；95%CI，0.39-0.97；P=0.04）的发生率降低。中性粒细胞减少症（RR，0.69；95%CI，0.36-1.29；P=0.24）和疲劳（RR，1.29；95%CI，0.95-1.77；P=0.11）在两组患者之间无显著差异。
在我们的荟萃分析中，仅在 S-1 方案中观察到生存获益显著，但结果仍有待确定。未来需要在临床试验中进一步验证最佳细胞毒性或靶向药物方案。
