Zhang Xiu-Wei, Ma Yu-Xiang, Sun Yang, Cao Yu-Bo, Li Qin, Xu Chong-An
Department of Pathology, The Fourth Affiliated Hospital, China Medical University, Shenyang, China.
Department of Oncologic Medicine, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China.
Target Oncol. 2017 Jun;12(3):309-321. doi: 10.1007/s11523-017-0486-5.
It remains controversial whether the addition of a second cytotoxic agent can further improve the therapeutic effect of gemcitabine monotherapy in advanced or metastatic pancreatic cancer (LA/MPC).
The objective of the present systematic review and meta-analysis was to investigate the efficacy and safety of gemcitabine-based doublet chemotherapy regimens compared to single-agent gemcitabine in the first-line treatment of unresectable LA/MPC.
We searched for randomized controlled trials (RCTs) of gemcitabine monotherapy versus gemcitabine in combination with a second cytotoxic agent in patients with LA/MPC. The last search date was December 31, 2016.
Twenty-seven RCTs were identified and included in the present systematic review and meta-analysis, involving a total of 7343 patients. The meta-analysis showed that gemcitabine-based combination therapy significantly improved overall survival (OS) (HR: 0.89; 95% confidence interval (CI): 0.85-0.94; P < 0.0001), progression-free survival (PFS) (HR: 0.80; 95% CI: 0.73-0.88; P < 0.0001), and overall response rate (ORR) (RR: 1.83; 95% CI: 1.62-2.07; P < 0.0001) in comparison to single-agent gemcitabine. Subgroup analysis suggested that the antitumor activity differed between gemcitabine-based combination regimens: doublet regimens of gemcitabine plus a taxoid, and gemcitabine plus a fluoropyrimidine, in particular an oral fluoropyrimidine, resulted in a significant OS benefit for the patients. However, the combination of gemcitabine with other cytotoxic agents, such as platinum compounds or topoisomerase inhibitors failed to reduce the mortality risk. Combination therapy caused more grade 3/4 toxicities, including neutropenia, thrombocytopenia, vomiting, diarrhea, and fatigue.
Gemcitabine-based doublet regimens demonstrated superiority over gemcitabine monotherapy in overall efficacy, but were associated with increased toxicity. Different gemcitabine-based combinations showed different antitumor activity, and doublet regimens of gemcitabine in combination with a taxoid or a fluoropyrimidine, in particular an oral fluoropyrimidine provided significant survival benefits in the first-line treatment of unresectable LA/MPC.
在晚期或转移性胰腺癌（LA/MPC）中，添加第二种细胞毒性药物是否能进一步提高吉西他滨单药治疗的疗效仍存在争议。
本系统评价和荟萃分析的目的是研究在一线治疗不可切除的LA/MPC时，与单药吉西他滨相比，基于吉西他滨的双联化疗方案的疗效和安全性。
我们检索了LA/MPC患者中吉西他滨单药治疗与吉西他滨联合第二种细胞毒性药物的随机对照试验（RCT）。最后检索日期为2016年12月31日。
共纳入27项RCT并进行本系统评价和荟萃分析，涉及7343例患者。荟萃分析显示，与单药吉西他滨相比，基于吉西他滨的联合治疗显著改善了总生存期（OS）（风险比[HR]：0.89；95%置信区间[CI]：0.85 - 0.94；P < 0.0001）、无进展生存期（PFS）（HR：0.80；95% CI：0.73 - 0.88；P < 0.0001）和总缓解率（ORR）（RR：1.83；95% CI：1.62 - 2.07；P < 0.0001）。亚组分析表明，基于吉西他滨的联合方案之间的抗肿瘤活性有所不同：吉西他滨加紫杉类药物以及吉西他滨加氟嘧啶，特别是口服氟嘧啶的双联方案，能为患者带来显著的总生存期获益。然而，吉西他滨与其他细胞毒性药物（如铂类化合物或拓扑异构酶抑制剂）联合使用未能降低死亡风险。联合治疗导致更多3/4级毒性反应，包括中性粒细胞减少、血小板减少、呕吐、腹泻和疲劳。
基于吉西他滨的双联方案在总体疗效上优于吉西他滨单药治疗，但毒性增加。不同的基于吉西他滨的联合方案显示出不同的抗肿瘤活性，吉西他滨与紫杉类药物或氟嘧啶，特别是口服氟嘧啶联合的双联方案在一线治疗不可切除的LA/MPC时能提供显著的生存获益。
