A systematic review and meta-analysis of users versus non-users: unveiling the influence of proton pump inhibitors on capecitabine efficacy in colorectal cancer

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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 I2 statistics.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; p < 0.001). Our results show that there seems to be no difference between users of PPIs and capecitabine in the colorectal cancer patients (HR 1.5922; 95% CI 0.9718–2.6086; p = 0.065). However, after sensitivity-adjusted analysis, PPI use was negatively associated with PPI use (HR 2.14; 95% CI 1.14–4.01; p < 0.001).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.

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