Trial reportThe oncologist2021
Proton Pump Inhibitor Use and the Efficacy of Chemotherapy in Metastatic Colorectal Cancer: A Post Hoc Analysis of a Randomized Phase III Trial (AXEPT).
Trial report in The oncologist, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- Do proton pump inhibitors affect the effectiveness of chemotherapy in colorectal cancer patients? A systematic review with meta-analysis.Frontiers in pharmacology · 2022Pooled it
- Proton pump inhibitors and colorectal cancer: A systematic review.World journal of gastroenterology · 2021Pooled it
- Proton pump inhibitors and all-cause mortality in colorectal cancer.Scientific reports · 2025Article
- Proton pump inhibitors reduce survival outcomes in patients treated with capecitabine: meta-analysis.Ecancermedicalscience · 2025Review
- Proton Pump Inhibitors Worsen Colorectal Cancer Outcomes in Patients Treated with Bevacizumab.Cancers · 2024Article
- Effects of vonoprazan and proton pump inhibitors on the efficacy of bevacizumab: a multicentre retrospective study.Clinical and experimental medicine · 2023Observational
- Drug-drug interactions with proton pump inhibitors in cancer patients: an underrecognized cause of treatment failure.ESMO open · 2023Review
- Influence of proton pump inhibitors on the pathological response of rectal cancer: a multicentre study.Ecancermedicalscience · 2023Article
- Review
- Re-thinking the possible interaction between proton pump inhibitors and capecitabine.Cancer chemotherapy and pharmacology · 2022Review
- Proton pump inhibitors affect capecitabine efficacy in patients with stage II-III colorectal cancer: a multicenter retrospective study.Scientific reports · 2022Observational
- Association between the Co-administration of Histamine HJournal of Cancer · 2022Article
- Proton Pump Inhibitors and Cancer: Current State of Play.Frontiers in pharmacology · 2022Review
- Use of omeprazole, the proton pump inhibitor, as a potential therapy for the capecitabine-induced hand-foot syndrome.Scientific reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundConcomitant use of proton pump inhibitors (PPIs) with capecitabine was suggested to be associated with poor outcomes in gastrointestinal cancers. We analyzed the differential impact of PPI use on capecitabine and fluorouracil using the data set from the AXEPT trial, a phase III randomized trial that demonstrated the noninferiority of mXELIRI (modified XELIRI: capecitabine plus irinotecan) to FOLFIRI (leucovorin, fluorouracil, and irinotecan), either with or without bevacizumab in patients with metastatic colorectal cancer. PATIENTS AND
methodsOut of the per-protocol set (n = 620), patients with information on concomitant medications (n = 482) were included in this post hoc analysis. PPI use was defined as concomitant exposure of capecitabine and the use of any PPI for 20% or more of the study period. The treatment-by-PPI-use interaction was examined after adjusting for stratification factors.
resultsOf the 482 patients, 49 (10.1%) used PPI. Among the PPI users, the mXELIRI group tended to have poorer overall survival compared with the FOLFIRI group. In contrast, among the nonusers, the overall survival of the mXELIRI group was significantly better than that of the FOLFIRI group. Similarly, a trend of worse progression-free survival with mXELIRI compared with FOLFIRI was observed in PPI users but not in nonusers. Treatment-by-PPI-use interaction was significant for overall survival and progression-free survival.
conclusionThe significant interaction between PPI use and the type of fluoropyrimidine in terms of overall and progression-free survival suggests that fluorouracil could be a more favorable option than capecitabine for patients with metastatic colorectal cancer using PPIs. IMPLICATIONS FOR PRACTICE: This study showed a significant interaction between the use of proton pump inhibitors (PPIs) and the type of fluoropyrimidines. This interaction mainly comes from the positive impact of PPIs in the survival outcomes in the fluorouracil arm rather than a negative impact of PPIs in the capecitabine arm. The possible drug-drug interaction shown in this study suggests that fluorouracil, rather than capecitabine, could be a more appropriate choice of fluoropyrimidine for patients who are taking PPIs in the treatment of metastatic colorectal cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.