AUTHOR=Lin Wan-Ying , Wang Shih-Syuan , Kang Yi-No , Porpiglia Andrea S. , Chang Yu , Huang Chin-Hsuan , Bhimani Ronak , Abdul-Lattif Eahab , Azmat Muneeba , Wang Tsu-Hsien , Lin Yu-Shiuan , Chang Yu-Cheng , Chi Kuan-Yu TITLE=Do proton pump inhibitors affect the effectiveness of chemotherapy in colorectal cancer patients? A systematic review with meta-analysis JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1048980 DOI=10.3389/fphar.2022.1048980 ISSN=1663-9812 ABSTRACT=
Proton pump inhibitors (PPI), one of the most commonly prescribed medications, carry a myriad of adverse events. For colorectal cancer (CRC) patients, it still remains unclear whether the concurrent use of proton pump inhibitors (PPI) would negatively affect chemotherapy. PubMed, Medline, Embase, and Cochrane Library were searched from inception to 10 June 2022, to identify relevant studies involving CRC patients receiving chemotherapy and reporting comparative survival outcomes between PPI users and non-users. Meta-analyses were performed using random-effects models. We identified 16 studies involving 8,188 patients (PPI = 1,789; non-PPI = 6,329) receiving either capecitabine-based or fluorouracil-based regimens. The overall survival (HR, 1.02; 95% CI, 0.91 to 1.15; I2 = 0%) and progression-free survival (HR, 1.15; 95% CI, 0.98 to 1.35; I2 = 29%) were similar between PPI users and non-users in patients taking capecitabine-based regimens, with low statis-tical heterogeneity. Although the subgroup analysis indicated that early-stage cancer patients taking capecitabine monotherapy with concurrent PPI had a significantly higher disease progression rate (HR, 1.96; 95% CI, 1.21 to 3.16; I2 = 0%) than those who did not use PPIs, both groups had comparable all-cause mortality (HR, 1.31; 95% CI, 0.75 to 2.29; I2 = 0%). On the other hand, there was little difference in both OS and PFS in both early- and end-stage patients taking capecitabine combination therapy between PPI users and non-users. Conversely, the use of concomitant PPI in patients taking fluorouracil-based regimens contributed to a marginally significant higher all-cause mortality (HR, 1.18; 95% CI, 1.00 to 1.40; I2 = 74%), but with high statistical heterogeneity. In conclusion, PPI has little survival influence on CRC patients treated with capecitabine-based regimens, especially in patients taking capecitabine combination therapy. Thus, it should be safe for clinicians to prescribe PPI in these patients. Although patients treated with fluorouracil-based regimens with concomitant PPI trended toward higher all-cause mortality, results were subject to considerable heterogeneity.