Effectiveness of 5-flurouracil-based neoadjuvant chemotherapy in locally-advanced gastric/gastroesophageal cancer: a meta-analysis

Abstract

Aim: To investigate the effectiveness of 5-flurouracil-based neoadjuvant chemotherapy (NAC) for gastroesophageal and gastric cancer by meta-analysis.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: Gastric cancer; Gastroesophageal cancer; Meta-analysis; Neoadjuvant chemotherapy.

Figure 1

Effect of neoadjuvant chemotherapy on overall survival rate. A: Overall survival rate (fixed effects model); B Overall survival rate (random effects model).

Figure 2

Publication bias in the included studies. Funnel plot analysis of potential publication bias. OR: Odds ratio.

Figure 3

Effect of neoadjuvant chemotherapy in progression free survival rate. A: Progression free survival rate (fixed effects model); B Progression free survival rate (random effects model).

Figure 4

Effect of neoadjuvant chemotherapy in tumor down-staging. A: Tumor down-staging rate (fixed effects model); B Tumor down-staging rate (random effects model).

Figure 5

Effect of neoadjuvant chemotherapy in tumor R-0 resection. A: R-0 resection rate (fixed effects model); B: R-0 resection rate (random effects model).

Figure 6

Effect of neoadjuvant chemotherapy in perioperative mortality. A: Perioperative mortality rate (fixed effects model); B: Perioperative mortality rate (random effects model).

Figure 7

Effect of neoadjuvant chemotherapy in postoperative complications. A: Postoperative complications rate (fixed effects model); B: Postoperative complications rate (random effects model).

Figure 8

Subgroup analysis showing different overall survival rates in patients with advanced gastric cancer.