INTRODUCTION: Colorectal cancer is the second leading cause of cancer-related deaths worldwide. The impact of proton pump inhibitors (PPIs) on patients taking capecitabine, an oral fluoropyrimidine, remains uncertain, despite their use by 20 to 55% of cancer patients. We investigated how PPIs affect the effectiveness of capecitabine in treating colorectal cancer. METHODS: We searched PubMed, Embase, and Web of Science databases for studies that investigated the use of PPI with capecitabine versus capecitabine alone. We used random-effects models for all endpoints. Heterogeneity was assessed using I RESULTS: We included 676 patients receiving capecitabine monotherapy. The overall progression/disease-free survival favored the PPI non-users (HR 2.1372
95% CI 1.4591-3.1306
CONCLUSION: Patients with colorectal cancer undergoing oral chemotherapy, specifically capecitabine, should be monitored for the use of PPIs. Therefore, the use of PPIs should be discouraged in clinical practice in these cases. PROTOCOL REGISTRATION: www.crd.york.ac.uk/prospero identifier is CRD42024498240.