Table 5.
Summary of treatment studies
| Author | Center | Study design | Cancer stage and type | Cancer treatment | PPI use (definition) | No. of patients | Results |
| Zhang et al[39] 2017 | Guangzhou, China | R | Stage II-III Rectal cancer | LCRT (46 Gy, Oxaliplatin + Capecitabine (2 cycles) | EOU = OME: 20 mg PO, min. OD for 6 d / 40 mg IVI, daily). EOG = total OME dose ≥ 200 mg1 | 125 | EOG vs non-EOG: 1DFS (3-year) = 77.1% vs 96.6%, P = 0.032, DFS (5-year) = 69.6% vs 46.7%, P = 0.032, OS (3-year) = 82.3% vs 96.6%, P = 0.092, OS (5-year) = 76.9% vs 89.5%, P = 0.092 EOU vs non-EOU: 1DFS (3-year) = 85.5% vs 77.8%, P = 0.658, DFS (5-year) = 75.6% vs 74.6%, P = 0.658, OS (3-year) = 90.3% vs 82.5%, P = 0.754, OS (5-year) = 82% vs 77.6%, P = 0.754 |
| Sun et al[40] 2016 | Edmonton, Canada | R | Stage I-III CRC | Adjuvant Capecitabine monotherapy | Any use during treatment (based on prescription data) | 298 | PPI-user vs non-users: RFS (5 years) = 74% vs 83%, P = 0.03; OS (5-year) = 81% vs 78%, P = 0.7. Multivariate RFS (5-year): HR (95%CI) = 1.65 (0.93-2.94), P = 0.09 |
| Wong et al[41] 2019 | Alberta, Canada | R | Stage II-III CRC | Adjuvant CapeOx or FOLFOX | Any use during treatment (based on prescription data) | 389 | PPI-users vs non-users, RFS (3-year): CapeOX = 69.5% vs 82.6%, P = 0.03; FOLFOX = 82.9% vs 61.7%, P = 0.7; Multivariate RFS: HR (95%CI) = 2.20 (1.14-4.25) P = 0.018; OS (3-year): CapeOX = 90.1% vs 91.2%, P = 0.345, FOLFOX = 77.4% vs 80.1%, P = 0.929 |
| Kichenadasse et al[42] 2021 | 6 clinical trials | Retrospective post-hoc analysis of RCT | Stage IV CRC | Fluoropyrimidine-based chemotherapy (± additional agents). Regimens differed across included trials | Minimum 7 d of use during study period | 5633 | OS: Significantly worse in PPI-users [HR (95%CI) = 1.20 (1.03-1.40)], P = 0.02; PFS: Significantly worse in PPI-users [HR (95%CI) = 1.20 (1.05-1.37)], P = 0.009 Various treatment subgroups did not influence OS and PFS |
| Kim et al[43] 2021 | China, Japan, South Korea (98 centers) | Retrospective post-hoc analysis of RCT | Stage IV CRC | mXELIRI or FOLFIRI (± Bevacizumab) | Use for ≥ 20% of study period | 620 | mXELIRI arm: No difference in OS or PFSFOLFIRI arm: Significantly better OS [HR (95%CI) = 0.5 (0.3-0.85), P = 0.11] and PFS [HR (95%CI) = 0.55 (0.33-0.91), P = 0.20] in PPI users |
1
Definitions of EOU and EOG are stated in the results section. CapeOX: Capecitabine plus oxaliplatin; CRC: Colorectal cancer; CI: Confidence interval; DFS: Disease free survival; EOU: Eligible omeprazole users; EOG: Effective omeprazole group; FOLFOX: 5-Fluorouracil, leucovorin, and oxaliplatin; FOLFIRI: 5-Fluorouracil, leucovorin, and irinotecan; HR: Hazard ratio; LCRT: Long-course chemoradiotherapy; mXELIRI: Capecitabine plus irinotecan; OME: Omeprazole; OS: Overall survival; PPI: Proton pump inhibitors; PFS: Progression free survival; RFS: Recurrence free survival; R: Retrospective cohort study; RCT: Randomized controlled trials.