Meta-Analysis
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World J Gastroenterol. Dec 28, 2012; 18(48): 7384-7393
Published online Dec 28, 2012. doi: 10.3748/wjg.v18.i48.7384
Effectiveness of 5-flurouracil-based neoadjuvant chemotherapy in locally-advanced gastric/gastroesophageal cancer: A meta-analysis
Lei Ge, Hai-Jiang Wang, Dong Yin, Cheng Lei, Jin-Feng Zhu, Xiao-Hui Cai, Guo-Qing Zhang
Lei Ge, Hai-Jiang Wang, Dong Yin, Cheng Lei, Jin-Feng Zhu, Xiao-Hui Cai, Guo-Qing Zhang, Department of Gastrointestinal Surgery, Tumor Hospital, Xinjiang Medical University, Urumqi 830011, Xinjiang Uyghur Autonomous Region, China
Author contributions: All authors made substantial contributions to the design of the study; Ge L designed the study and prepared the manuscript; Wang HJ revised the manuscript; Zhang GQ and Yin D designed the study; Ge L, Zhu JF, Lei C and Cai XH performed the research and analyzed the data; Wang HJ and Zhang GQ supervised the whole study; all authors read and approved the final version to be published.
Correspondence to: Guo-Qing Zhang, MD, Department of Gastrointestinal Surgery, Tumor Hospital, Xinjiang Medical University, No. 789, Suzhou East Road, Urumqi 830000, Xinjiang Uyghur Autonomous Region, China. zgqprofessor@sina.com
Telephone: +86-991-7968003 Fax: +86-991-7968111
Received: July 14, 2012
Revised: October 29, 2012
Accepted: November 6, 2012
Published online: December 28, 2012
Processing time: 199 Days and 21.8 Hours
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: Gastroesophageal cancer; Gastric cancer; Neoadjuvant chemotherapy; Meta-analysis