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.