AB61. A systematic review of S-1-based therapy versus 5-FU-based therapy in Chinese patients with advanced gastric cancer

Objective: 5-Fluorouracil (5-FU) remains an essential part of the treatment of advanced gastric cancer (AGC), with a relatively low response rate and high incidence of toxicities. Clinical trials have shown that S-1, a novel oral prodrug of 5-FU, achieved a high response rate with a lower incidence of toxicities in foreign patients with AGC. In recent years, S-1 has also been widely used in China. The aim of this study is to systematically review the clinical efficacy and safety of S-1-based therapy versus 5-FU-based therapy in Chinese patients with AGC.

Methods: Randomized controlled trials (RCTs), S-1-based therapy versus 5-FU-based therapy (mono or combined chemotherapy with S-1 versus 5-FU or S-1 plus chemotherapy drugs versus 5-FU plus the same chemotherapy drugs) in Chinese patients with AGC, were searched in online databases CNKI, WANFANG DATA, and PubMed from inception to April 2013.Two reviewers independently screened studies according to the inclusion and exclusion criteria, assessed quality of the included studies and extracted the data. Meta-analysis was performed by RevMan 5.0.2.

Results: Twenty-seven RCTs (including 3 multicenter RCTs) with 1,919 participants were identified in the analysis (1,000 patients were in the S-1-based group and 919 patients in the 5-FU-based group). All included RCTs reported short-term effects and meta-analysis showed that S-1 can improve objective response rate [OR=2.15, 95% CI (1.77, 2.62), P<0.00001] and disease control rate [OR=1.95, 95% CI (1.56, 2.44), P<0.00001]. Only 4 RCTs reported 1-year survival rate and meta-analysis showed that the difference was not statistically significant [OR=1.51, 95% CI (0.96, 2.38), P=0.08]. There were respectively 9, 9 and 5 RCTs reporting median survival time (OS), time-to-progression (TTP) and progression-free survival (PFS), the data of which cannot be pooled in a meta-analysis. Out of these RCTs, 2, 3 and 2 reported no significant differences between the two groups; however, the remaining 7, 6 and 3 RCTs reported that median OS, TTP and PFS in the S-1 group were significantly longer than those in the 5-FU group. With regard to clinical benefit response, S-1 was superior to 5-FU in the improvement of KPS score [OR=2.16, 95% CI (1.48, 3.14), P<0.0001]. In terms of safety, S-1 can significantly reduce the incidences of grade 3/4 toxicities, including leukocytopenia [0.57, 95% CI (0.40, 0.83), P=0.003], thrombocytopenia [0.43, 95% CI (0.27, 0.69), P=0.0005], nausea/vomiting [0.47, 95% CI (0.33, 0.68), P<0.0001], diarrhea/constipation [0.61, 95% CI (0.40, 0.92), P=0.02], liver injury [0.33, 95% CI (0.16, 0.69), P=0.003], stomatitis [0.40, 95% CI (0.24, 0.66), P=0.0004], peripheral neuropathy [0.44, 95% CI (0.24, 0.81), P=0.008] and hand-foot syndrome [0.35, 95% CI (0.15, 0.84), P=0.02].

Conclusions: For Chinese patients with AGC, S-1 can significantly improve the objective response rate and disease control rate, and meanwhile reduce the incidences of common grade 3/4 toxicities; whereas benefits in overall survival and progression-free survival need to be confirmed by more well-designed, high-quality and large-scale RCTs.

Keywords: Stomach neoplasms; S-1; fluorouracil; systematic review; meta-analysis