Department of Gastrointestinal Surgery, Tumor Hospital, Xinjiang Medical University, Urumqi 830011, Xinjiang Uyghur Autonomous Region, China.
World J Gastroenterol. 2012 Dec 28;18(48):7384-93. doi: 10.3748/wjg.v18.i48.7384.
To investigate the effectiveness of 5-flurouracil-based neoadjuvant chemotherapy (NAC) for gastroesophageal and gastric cancer by meta-analysis.
MEDLINE and manual searches were performed to identify all published randomized controlled trials (RCTs) investigating the efficacy of the flurouracil-based NAC for gastroesophageal and gastric cancer, and RCTs of NAC for advanced gastroesophageal and gastric cancer vs no therapy before surgery. Studies that included patients with metastases at enrollment were excluded. Primary endpoint was the odds ratio (OR) for improving overall survival rate of patients with gastroesophageal and gastric cancer. Secondary endpoints were the OR of efficiency for down-staging tumor and increasing R0 resection in patients with gastroesophageal and gastric cancer. Safety analyses were also performed. The OR was the principal measurement of effect, which was calculated as the treatment group (NAC plus surgery) vs control group (surgery alone) and was presented as a point estimate with 95% confidence intervals (CI). All calculations and statistical tests were performed using RevMan 5.1 software.
Seven RCTs were included for the analysis. A total of 1249 patients with advanced gastroesophageal and gastric cancer enrolled in the seven trials were divided into treatment group (n = 620) and control group (n = 629). The quality scores of the RCTs were assessed according to the method of Jadad. The RCT quality scores ranged from 2 to 7 (5-point scale), with a mean of 3.75. The median follow-up time in these studies was over 3 years. The meta-analysis showed that NAC improved the overall survival rate (OR 1.40, 95%CI 1.11-1.76; P = 0.005), which was statistically significant. The 3-year progression-free survival rate was significantly higher in treatment group than in control group (37.7% vs 27.3%) (OR 1.62, 95%CI 1.21-2.15; P = 0.001). The tumor down-stage rate was higher in treatment group than in control group (55.76% vs 41.38%) (OR 1.77, 95%CI 1.27-2.49; P = 0.0009) and the R0 resection rate of the gastroesophageal and gastric cancer was higher in treatment group than in control group (75.11% vs 68.56%) (OR 1.38, 95%CI 1.03-1.85; P = 0.03), with significant differences. No obvious safety concerns about mortality and complications were raised in these trials. There were no statistically significant differences in perioperative mortality (5.08% vs 4.86%) (OR 1.05, 95%CI 0.57-1.94; P = 0.87 fixed-effect model) and in the complication rate between the two groups (13.25% vs 9.66%) (OR 1.40, 95%CI 0.91-2.14; P = 0.12 fixed-effect model). Trials showed that patients from Western countries favored NAC compared with those from Asian countries (OR 1.40, 95%CI 1.07-1.83). Monotherapy was inferior to multiple chemotherapy (OR 1.40, 95%CI 1.07-1.83). Intravenous administration of NAC was more advantageous than oral route (OR 1.41, 95%CI 1.09-1.81).
Flurouracil-based NAC can safely improve overall survival rate of patients with gastroesophageal/gastric cancer. Additionally, NAC can down the tumor stage and improve R0 resection.
通过荟萃分析研究 5-氟尿嘧啶为基础的新辅助化疗（NAC）在胃食管和胃癌中的疗效。
通过 MEDLINE 和手工检索，确定所有已发表的随机对照试验（RCT），这些试验调查了基于氟尿嘧啶的 NAC 对胃食管和胃癌的疗效，以及 NAC 治疗晚期胃食管和胃癌与术前无治疗的 RCT。排除了在入组时存在转移的患者的研究。主要终点是提高胃食管和胃癌患者总生存率的优势比（OR）。次要终点是肿瘤降期和增加胃食管和胃癌患者 R0 切除的 OR。还进行了安全性分析。OR 是主要的疗效测量，计算为治疗组（NAC 加手术）与对照组（单独手术），并以点估计值和 95%置信区间（CI）表示。所有计算和统计检验均使用 RevMan 5.1 软件进行。
共有 7 项 RCT 纳入分析。这 7 项试验共纳入 1249 例晚期胃食管和胃癌患者，分为治疗组（n = 620）和对照组（n = 629）。根据 Jadad 方法评估 RCT 的质量评分。RCT 的质量评分范围从 2 到 7（5 分制），平均为 3.75。这些研究的中位随访时间超过 3 年。荟萃分析显示，NAC 提高了总生存率（OR 1.40，95%CI 1.11-1.76；P = 0.005），具有统计学意义。治疗组 3 年无进展生存率明显高于对照组（37.7%比 27.3%）（OR 1.62，95%CI 1.21-2.15；P = 0.001）。治疗组肿瘤降期率高于对照组（55.76%比 41.38%）（OR 1.77，95%CI 1.27-2.49；P = 0.0009），治疗组胃食管和胃癌的 R0 切除率高于对照组（75.11%比 68.56%）（OR 1.38，95%CI 1.03-1.85；P = 0.03），差异有统计学意义。这些试验没有明显的关于死亡率和并发症的安全性问题。两组围手术期死亡率（5.08%比 4.86%）（OR 1.05，95%CI 0.57-1.94；P = 0.87 固定效应模型）和并发症发生率（13.25%比 9.66%）（OR 1.40，95%CI 0.91-2.14；P = 0.12 固定效应模型）无统计学差异。试验表明，来自西方国家的患者比来自亚洲国家的患者更喜欢 NAC（OR 1.40，95%CI 1.07-1.83）。单药治疗不如多药化疗（OR 1.40，95%CI 1.07-1.83）。静脉注射 NAC比口服途径更有利（OR 1.41，95%CI 1.09-1.81）。
基于氟尿嘧啶的 NAC 可以安全地提高胃食管/胃癌患者的总生存率。此外，NAC 可以降低肿瘤分期，提高 R0 切除率。
