Proton pump inhibitor use and survival in patients with newly diagnosed glioblastoma
Proton pump inhibitors (PPI) are often prescribed to prevent steroid-induced gastritis and peptic ulcer disease in patients with glioblastoma. Yet, these drugs may enhance the activity of aldehyde dehydrogenase 1 A1 (ALDH1A1), which has been linked to protection from oxidative stress, radiotherapy,...
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
November 25, 2025
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| In: |
JAMA network open
Year: 2025, Volume: 8, Issue: 11, Pages: 1-13 |
| ISSN: | 2574-3805 |
| DOI: | 10.1001/jamanetworkopen.2025.45578 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1001/jamanetworkopen.2025.45578 Verlag, kostenfrei, Volltext: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2841819#250681476 
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| Author Notes: | Emilie Le Rhun, MD, PhD; Debaleena Sain, PhD; Sara C. Erridge, MD; David A. Reardon, MD; Giuseppe Minniti, MD; Patrick Roth, MD; Wolfgang Wick, MD; Burt Nabors, MD; John Sampson, MD; Warren Mason, MD; Tim Cloughesy, MD; Jacob C. Reijneveld, MD; Roger Stupp, MD; Matthias Preusser, MD; Thierry Gorlia, PhD; Michael Weller, MD |
| Summary: | Proton pump inhibitors (PPI) are often prescribed to prevent steroid-induced gastritis and peptic ulcer disease in patients with glioblastoma. Yet, these drugs may enhance the activity of aldehyde dehydrogenase 1 A1 (ALDH1A1), which has been linked to protection from oxidative stress, radiotherapy, and chemotherapy.To explore the associations of the use of potent ALDH1A1-activating PPIs (PA-PPIs) and other antacid drugs with outcomes in patients with newly diagnosed glioblastoma.This meta-analysis was a secondary analysis of individual prospectively captured patient data using a dataset of 5 randomized clinical trials conducted between 2008 and 2020. Participants included patients with a new diagnosis of glioblastoma. Data analysis was completed in November 2024.We assessed drug use at baseline and defined 3 landmarks: start of temozolomide maintenance cycles 1 (landmark 1) and 4 (landmark 2), and end of cycle 6 (landmark 3).The primary outcome measures were progression-free survival (PFS) and overall survival (OS) from baseline and from the start of each corresponding landmark time.The study population included 2981 patients (1858 [62.3%] male; median [range] age, 58 [18-85] years). On univariate analysis, patients treated with PA-PPI had worse PFS and OS at all 4 time points. The multivariate analysis accounting for age, sex, performance status, steroid use, extent of resection, and MGMT status confirmed a difference for PFS at landmarks 1 (hazard ratio [HR], 1.14 [95% CI, 1.01-1.28]), 2 (HR, 1.26 [95% CI, 1.09-1.44]), and 3 (HR, 1.31 [95% CI, 1.10-1.56]), and for OS at landmarks 1 (HR, 1.34 [95% CI, 1.08-1.66]) and 2 (HR, 1.14 [95% CI, 1.01-1.29]). No such association was seen for the use of other antacid drugs. The negative association of PA-PPI use with PFS and OS was observed independently of MGMT promoter methylation and steroid use.In this meta-analysis of patients with newly diagnosed glioblastoma, PPI use was associated with inferior survival outcomes. These findings suggest that PA-PPI use should be discouraged in patients with glioblastoma, since alternative agents are available and a detrimental effect cannot be excluded. Translational research studies should explore whether PPI-induced activity of ALDH mediates the potential adverse effects of PPI in glioblastoma.. |
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| Item Description: | Gesehen am 10.03.2026 |
| Physical Description: | Online Resource |
| ISSN: | 2574-3805 |
| DOI: | 10.1001/jamanetworkopen.2025.45578 |