Neoadjuvant Chemotherapy for Gastric Cancer

A Meta-analysis of Randomized, Controlled Trials

Yi Liao; Zu-li Yang; Jun-sheng Peng; Jun Xiang; Jian-ping Wang

Disclosures

J Gastroenterol Hepatol. 2013;28(5):777-782. 

In This Article

Abstract and Introduction

Abstract

Background and Aim: Although the effect of neoadjuvant chemotherapy in gastric cancer has been extensively studied, the data of survival benefit are still controversial. The purpose of this work was to assess the effectiveness of neoadjuvant chemotherapy followed by surgery in patients with gastric cancer.

Methods: We searched systematically electronic through the databases of PUBMED, EMBASE, China Biological Medicine, and China National Knowledge Infrastructure Whole Article for studies published from 1975. Two reviewers independently evaluated the relevant reports and searched manually reference from these reports for additional trials. Outcomes assessed by meta-analysis included overall survival rate, progression-free survival rate, R0 resection rate, downstaging effect, postoperative complications, and perioperative mortality.

Results: Six randomized, controlled trials with 781 patients were included in the meta-analysis. Odds ratio (95% confidence interval; P-value), expressed as neoadjuvant chemotherapy and surgery versus surgery alone, was 1.16 (0.85–1.58; P = 0.36) for overall survival, 1.24 (0.78–1.96; P = 0.36) for R0 resection, 1.25 (0.75–2.09; P = 0.39) for postoperative complications, and 3.60 (0.59–22.45; P = 0.17) for perioperative mortality.

Conclusions: Compared with surgery alone, neoadjuvant chemotherapy followed by surgery was not associated with a higher rate of overall survival or complete resection (R0 resection). It does not increase treatment-related morbidity and mortality. This meta-analysis did not demonstrate a survival benefit for the combination of neoadjuvant chemotherapy and surgery.

Introduction

Although the incidence and cancer-related mortality have been steadily decreasing during the past century, gastric cancer remains one of the most common malignancies worldwide.[1,2] The prognosis of patients with gastric cancer is determined by the stage of the disease. Five-year survival rate of early-stage gastric cancer is up to 90% after curative resection.[3] Unfortunately, about two-thirds of the patients have evidence of advanced disease at the time of initial presentation.[4] The result for advanced gastric cancer is poor. Even after macroscopic resection, 60% of the patients in this patient population will develop local recurrence or distant metastases,[5,6] and they have a 5-year survival rate of around 25%.[7]

In order to better control of the local relapse and increase in survival time of advanced patients, the role of neoadjuvant chemotherapy (NAC) is currently being investigated with different protocols. Many phase II and III trials, including randomized, controlled trials (RCTs), have been conducted and completed. However, the results of these trials were conflicting, making the role of NAC controversial.[8–10] The first prospective randomized trial conducted by the Dutch Gastric Cancer Group failed to demonstrate a survival benefit from the NAC.[11] The British Medical Research Council Adjuvant Gastric Cancer Infusional Chemotherapy phase III trial,[12] and French Fédération Nationale des Centres de Lutte contre le Cancer and Fédération Francophone de Cancérologie Digestive multicenter phase III trial[13] evaluated the effects of a combination of preoperative and postoperative chemotherapy compared with surgery alone in patients with resectable adenocarcinoma of the stomach or lower esophagus. In stark contrast, both trials provided promising evidences in support of perioperative chemotherapy. However, because of the design of the trials, it was impossible to access the relative contribution of the preoperative as opposed to the postoperative component with respect to survival benefit.

The current meta-analysis is to determine if there is a benefit of preoperative chemotherapy compared with surgery alone from available RCTs for patients with gastric cancer.

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