Chemotherapy in advanced gastric cancer: what is the evidence?

Background: Systemic chemotherapy is the major treatment option for the majority of gastric cancer patients. Uncertainty remains regarding the choice of the regimen Objectives: To assess the effect of 1. Chemotherapy versus best supportive care (BSC), 2. Combination versus single agent chemotherapy 3. The following different combination chemotherapy regimens: a.) 5-FU/cisplatin combinations with versus without anthracyclines b.) 5-FU/anthracycline combinations with versus without anthracyclines Search strategy: We searched: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, proceedings from DDW, ECCO, ESMO, ASCO until February 2004. Selection criteria: Randomised controlled trials on systemic intravenous chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapies as above in advanced gastric cancer. Main results: 24 randomised trials with a total number of 3304 patients are included in this meta-analysis. Analysis of 1. Chemotherapy versus BSC consistently demonstrated a significant benefit in terms of overall survival in favour of the group receiving chemotherapy (HR 0.39, 95%CI 0.28–0.52). Analysis of 2. Combination versus single-agent chemotherapy provides evidence for a survival benefit in favour of combination chemotherapy (HR 0.83, 95%CI 0.74–0.93), which is achieved at the price of increased toxicity. When comparing 3a.) 5-FU/cisplatin-containing combination therapy regimens with anthracyclines versus those without anthracyclines (HR 0.77, 95%CI 0.62–0.95) and 3b.) 5-FU/anthracycline-containing combinations with cisplatin versus those without cisplatin (HR 0.83, 95%CI 0.76–0.91), both demonstrate a significant survival benefit for regimens including 5-FU, anthracyclines and cisplatin. Conclusions: Chemotherapy significantly improves survival in comparison to best supportive care. In addition, combination chemotherapy improves survival compared to single-agent 5-FU, but the effect size is much smaller. Among the combination chemotherapy regimens studied, best survival results are achieved with regimens containing 5-FU, anthracyclines and cisplatin such as ECF which also appears to be best tolerated.Supported by the german ministry for education and research (BMBF).

Keywords: chemotherapy - gastric cancer - meta-analysis