Capecitabine for the treatment for advanced gastric cancer: Efficacy, safety and ethnicity

Abstract

What is known and Objective: Capecitabine- and 5-fluorouracil (5-FU)-based regimens are widely used for the treatment for advanced gastric cancer (AGC). We aimed to compare the efficacy of the two regimens for both Caucasian and Asian subjects, through a meta-analysis of the available trial evidence. Methods: We searched PubMed, ASO, ECCO, ESMO, Wanfang database (Chinese), CNKI (Chinese), Weipu database (Chinese) and J-STAGE (Japanese) using combinations of keywords, including 'capecitabine', '5-fluorouracil', 'chemotherapy', 'stomach neoplasms' and 'gastric cancer'. We identified relevant trial evidence and pooled the results on both efficacy and adverse events. Results and Discussion: Capecitabine-based chemotherapy for AGC prolonged the overall survival (OS; 10.7 months vs. 9.5 months, P = 0.03) and enhanced the response rate (RR; OR = 1.32; 95% CI, 1.11-1.57; P = 0.002) over 5-FU-based chemotherapy. Similar trends were observed in both Caucasian and Asian patients. Capecitabine-based regimens were associated with reduced incidence rates of grade 3 or grade 4 leukopenia (OR = 0.42; P = 0.005), stomatitis (OR = 0.43; P = 0.004) and nausea and vomiting (OR = 0.60; P = 0.002) compared with 5-FU-based treatment. Incidence of haematological toxicity such as anaemia (OR = 0.88; P = 0.53), thrombocytopenia (OR = 0.58; P = 0.06), neutropenia (OR = 1.03; P = 0.78) and treatment-related mortality was similar between capecitabine- and 5-FU-based treatments. Higher frequency of grade 3 or grade 4 hand-foot syndrome (HFS; OR = 2.45; P = 0.0007) was observed in capecitabine-based combination therapies. Asian patients with AGC receiving capecitabine-based combination therapies showed less frequent occurrence of grade 3 or grade 4 gastrointestinal toxicity including nausea and vomiting (OR = 0.24; P = 0.0002) and stomatitis (OR = 0.33; P = 0.02) than those receiving 5-FU-based regimens. These differences in GI toxicity between treatment regimens were not significant in Caucasian subjects. No significant difference was found for the occurrence of anaemia (Caucasian subgroup: OR = 0.97, P = 0.88; Asian subgroup: OR = 0.63, P = 0.29), neutropenia (Caucasian subgroup: OR = 1.16, P = 0.27; Asian subgroup: OR = 0.75, P = 0.21) or thrombocytopenia (Caucasian subgroup: OR = 0.62, P = 0.18; Asian subgroup: OR = 0.51, P = 0.17) between the two ethnic subgroups. What is new and Conclusion: Capecitabine-based chemotherapy strategies show prolonged OS and enhanced ORR compared with traditional 5-FU-based treatments and therefore should be considered as one of the first choices for treatment for AGC. Asian patients also showed less grade 3 or grade 4 gastrointestinal toxicity with the capecitabine-based regimens. © 2011 Blackwell Publishing Ltd.