ArticleInvestigational new drugs2014
A phase I trial of pantoprazole in combination with doxorubicin in patients with advanced solid tumors: evaluation of pharmacokinetics of both drugs and tissue penetration of doxorubicin.
Article in Investigational new drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Esomeprazole covalently interacts with the cardiovascular enzyme dimethylarginine dimethylaminohydrolase: Insights into the cardiovascular risk of proton pump inhibitors.Biochimica et biophysica acta. General subjects · 2022Pooled it
- Repurposing pantoprazole in combination with systemic therapy in advanced head and neck squamous cell carcinoma: a phase I/II randomized study.Medical oncology (Northwood, London, England) · 2023Trial
- Trial
- The multifaceted functions of selective autophagy in cancer: molecular basis, consequences, and clinical prospects.Molecular cancer · 2026Review
- Proton pump inhibitor attenuates acidic microenvironment to improve the therapeutic effects of MSLN-CAR-T cells on the brain metastasis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Oral Carbon Monoxide Enhances Autophagy Modulation in Prostate, Pancreatic, and Lung Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- PaSTe. Blockade of the Lipid Phenotype of Prostate Cancer as Metabolic Therapy: A Theoretical Proposal.Current medicinal chemistry · 2024Review
- The relationship between autophagy and PD-L1 and their role in antitumor therapy.Frontiers in immunology · 2023Review
- Combination of esomeprazole and pirfenidone enhances antifibrotic efficacy in vitro and in a mouse model of TGFβ-induced lung fibrosis.Scientific reports · 2022Article
- Article
- Esomeprazole attenuates inflammatory and fibrotic response in lung cells through the MAPK/Nrf2/HO1 pathway.Journal of inflammation (London, England) · 2021Article
- Autophagy in tumour immunity and therapy.Nature reviews. Cancer · 2021Review
- Dual Roles of Autophagy and Their Potential Drugs for Improving Cancer Therapeutics.Biomolecules & therapeutics · 2020Review
- Article
- Crosstalks between inflammasome and autophagy in cancer.Journal of hematology & oncology · 2020Review
- Emerging agents that target signaling pathways in cancer stem cells.Journal of hematology & oncology · 2020Review
- Multiple Facets of Autophagy and the Emerging Role of Alkylphosphocholines as Autophagy Modulators.Frontiers in pharmacology · 2020Review
- Combination of an Autophagy Inducer and an Autophagy Inhibitor: A Smarter Strategy Emerging in Cancer Therapy.Frontiers in pharmacology · 2020Review
- Brain tumor acidification using drugs simultaneously targeting multiple pH regulatory mechanisms.Journal of neuro-oncology · 2019Article
- Diverse Stakeholders of Tumor Metabolism: An Appraisal of the Emerging Approach of Multifaceted Metabolic Targeting by 3-Bromopyruvate.Frontiers in pharmacology · 2019Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn preclinical models, the proton pump inhibitor pantoprazole enhances the antitumor activity of chemotherapeutic agents by improving drug distribution and by inhibiting autophagy.
methodsPatients with advanced solid tumors (n = 24) received doxorubicin 60 mg/m(2) and escalating doses of pantoprazole (80, 160, 240 and 360 mg) administered intravenously prior to doxorubicin. Blood samples were collected for pharmacokinetic studies. An optional biopsy was performed to evaluate doxorubicin concentration and pharmacodynamic markers of drug activity.
resultsTwenty-four patients participated in the study (17 in the dose escalation phase and 7 in the dose expansion). Three patients experienced a dose limiting toxicity (grade 3 fatigue in the three cases), one patient at dose level 3 (pantoprazole 240 mg) and two patients at dose level 4 (pantoprazole 360 mg). Dose level 4 was considered to exceed the maximum tolerated dose. The recommended phase II dose was pantoprazole 240 mg and doxorubicin 60 mg/m(2). The most commonly observed toxicities included fatigue, neutropenia and leukopenia. Two patients achieved a confirmed partial response. Median maximum serum concentration of pantoprazole was 84.3 μM at 1-2 h after injection of pantoprazole 240 mg. No drug-drug interaction was observed. A single on-treatment tumor biopsy showed a sharply decreasing gradient in doxorubicin concentration and associated activity markers with increasing distance from tumor blood vessels.
conclusionAdministration of high doses of pantoprazole in combination with doxorubicin is feasible. The recommended phase II dose of pantoprazole, 240 mg, will be evaluated in combination with docetaxel as first line in patients with castration-resistant prostate cancer.
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Registered trials
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