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

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.

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.

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.

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.