中国循证医学杂志

中国循证医学杂志

卡培他滨联合化疗治疗晚期胰腺癌疗效与安全性的系统评价

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目的 系统评价卡培他滨联合化疗方案治疗晚期胰腺癌的疗效和安全性。 方法 计算机检索 PubMed、The Cochrane Library、CBM、CNKI 和 WanFang Data 数据库,搜集卡培他滨联合化疗方案与不含卡培他滨的化疗方案比较治疗晚期胰腺癌的随机对照试验(RCT),检索时限均从建库至 2017 年 12 月 1 日。由 2 位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用 RevMan 5.3 软件进行 Meta 分析。 结果 共纳入 6 个 RCT,1 317 例患者。Meta 分析结果显示:卡培他滨联合化疗方案的中位生存期[HR=0.86,95%CI(0.77,0.96),P=0.006]、疾病无进展生存期[HR=0.83,95%CI(0.75,0.91),P=0.000 2]和治疗总有效率[RR=1.64,95%CI(1.27,2.11),P=0.000 1]明显优于不含卡培他滨的化疗方案;但在 1 年生存率方面,两组差异无统计学意义。在毒副作用方面,卡培他滨联合化疗方案的 3~4 级中性粒细胞减少、口腔炎及手足综合征的发生率高于不含卡培他滨的化疗方案(P 均<0.05)。 结论 卡培他滨联合化疗方案可延长晚期胰腺癌患者的总生存期及疾病无进展生存期,提高了治疗总有效率;但会增加毒副反应,且 1 年以后的远期生存无明显改善。受纳入研究数量和质量的限制,上述结论尚待开展更多高质量研究予以验证。

Objective To evaluate the efficacy and safety of capecitabine combination chemotherapy for advanced pancreatic cancer. Methods The Cochrane Library, PubMed, EMbase, CBM, CNKI and WanFang Data databases were searched to collect randomized controlled trials (RCTs) on capecitabine combination chemotherapy for advanced pancreatic cancer from inception to December, 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, data were analyzed by using RevMan 5.3 software. Results Six RCTs were included. The results of meta-analysis showed that compared with the control group, capecitabine combination chemotherapy extended the overall survival (HR=0.86, 95%CI 0.77 to 0.96, P=0.006) and disease progression-free survival (HR=0.83, 95%CI 0.75 to 0.91, P=0.000 2). Moreover, the objective response rate was significantly increased in capecitabine combination chemotherapy (RR=1.64, 95%CI 1.27 to 2.11, P=0.000 1). The results of 3–4 toxic side effects of 6 RCTs indicated that the incidence of neutropenia, stomatitis and hand-foot syndrome of capecitabine combination chemotherapy were obviously higher than those in the control group (P<0.05). Conclusions Capecitabine combination chemotherapy extend the overall survival and disease progression-free survival, and improve the objective response rate. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify above conclusion.

关键词: 晚期胰腺癌; 卡培他滨; 吉西他滨; 随机对照试验; 系统评价

Key words: Advanced pancreatic cancer; Capecitabine; Gemcitabine; Randomized controlled trial; Systematic review

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1. 张师容, 靳伟, 刘亮, 等. 2017 年胰腺癌基础研究及诊疗新进展. 中国癌症杂志, 2018, 28(1): 1-10.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin, 2018, 68(1): 7-30.
3. Kamisawa T, Wood LD, Itoi T, et al. Pancreatic cancer. Lancet, 2016, 388(10039): 73-85.
4. 中华医学会外科学分会胰腺外科学组. 胰腺癌诊治指南(2014). 中华外科杂志, 2014, 52(12): 881-887.
5. Ottaiano A, Capozzi M, De Divitiis C, et al. Gemcitabine mono-therapy versus gemcitabine plus targeted therapy in advanced pancreatic cancer: a meta-analysis of randomized phase III trials. Acta Oncol, 2017, 56(3): 377-383.
6. Cao C, Kuang M, Xu W, et al. Gemcitabine plus S-1: a hopeful frontline treatment for Asian patients with unresectable advanced pancreatic cancer. Jpn J Clin Oncol, 2015, 45(12): 1122-1130.
7. Irigoyen A, Gallego J, Guillén Ponce C, et al. Gemcitabine-erlotinib versus gemcitabine- erlotinib-capecitabine in the first-line treatment of patients with metastatic pancreatic cancer: Efficacy and safety results of a phase IIb randomised study from the Spanish TTD Collaborative Group. Eur J Cancer, 2017, 75: 73-82.
8. Lee HS, Chung MJ, Park JY, et al. A randomized multicenter phase III study of gemcitabine combined with capecitabine versus gemcitabine alone as first-line chemotherapy for advanced pancreatic cancer in South Korea. Medicine (Baltimore), 2017, 96(1): e5702.
9. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary. Control Clin Trials, 1996, 17(1): 1-12.
10. Cunningham D, Chau I, Stocken DD, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol, 2009, 27(33): 5513-5518.
11. Herrmann R, Bodoky G, Ruhstaller T, et al. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol, 2007, 25(16): 2212-2217.
12. Scheithauer W, Schüll B, Ulrich-Pur H, et al. Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized phase II trial. Ann Oncol, 2003, 14(1): 97-104.
13. 王健, 赵云超, 韩娜. 吉西他滨联合卡培他滨与吉西他滨单药治疗晚期胰腺癌的疗效. 中国老年学杂志, 2011, 31(16): 3197-3198
14. Middleton G, Palmer DH, Greenhalf W, et al. Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial. Lancet Oncol, 2017, 18(4): 486-499.
15. Hammel P, Huguet F, van Laethem JL, et al. Effect of chemoradiotherapy vs. chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the lap07 randomized clinical trial. JAMA, 2016, 315(17): 1844-1853.
16. Ottaiano A, Capozzi M, De Divitiis C, et al. Gemcitabine mono-therapy versus gemcitabine plus targeted therapy in advanced pancreatic cancer: a meta-analysis of randomized phase III trials. Acta Oncol, 2017, 56(3):377-383.
17. Satoi S, Fujii T, Yanagimoto H, et al. Multicenter Phase II study of intravenous and intraperitoneal paclitaxel with S-1 for pancreatic ductal adenocarcinoma patients with peritoneal metastasis. Ann Surg, 2017, 265(2): 397-401.