Acid-suppressive agents and survival outcomes in patients with cancer: a systematic review and meta-analysis

Background Patients with cancer often receive acid-suppressive agents (ASAs) to treat common gastroesophageal reflux and peptic ulcer diseases. Our systematic review addresses the association between ASAs and survival outcomes in these patients. Methods We searched MEDLINE, EMBASE, and Cochrane until December 2019, including randomized controlled trials (RCTs), quasi-RCTs, and observational studies concerning ASAs that reported progression-free survival (PFS) and/or overall survival (OS). We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) using the random-effects model, and assessed heterogeneity with I 2 statistic. Results We included 45,626 patients from 7 RCTs and 18 observational studies, including esophageal/gastric, colorectal, pancreatic, lung, breast, prostate, kidney, and other cancers. Five studies showed that ASAs in lung cancer patients received tyrosine kinase inhibitors (TKIs) had significantly worse PFS (HR 1.64, 95% CI 1.14 − 2.37, I 2 = 57%) and OS (HR 1.13, 95% CI 1.05 − 1.21, I 2 = 0%) than nonusers. Each of five studies found no significant association between ASAs and OS in esophageal/gastric (HR 0.91, 95% CI 0.77 − 1.09, I 2 = 32%) or colorectal cancer patients (HR 1.33, 95% CI 0.96− 1.85, I 2 = 0%). ASAs were not significantly associated with an OS in patients with kidney cancer (HR 1.04, 95% CI 0.96 − 1.13, I 2 = 28%). Conclusions Meta-analysis showed that ASAs significantly associated with an increased mortality risk in lung cancer patients treated TKIs, but not in patients with esophageal/gastric, colorectal, or kidney cancer. Until further studies confirm these results, caution should be used when administering ASAs and TKIs to patients with lung cancer.