ArticleJournal of neuro-oncology2021
A Phase I clinical trial of dose-escalated metabolic therapy combined with concomitant radiation therapy in high-grade glioma.
Article in Journal of neuro-oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 3 of them syntheses that pooled it.
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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
34 citing papers in PubMed, 3 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- Metabolic modulation of glioblastoma by dietary intervention: a systematic review.Journal of neuro-oncology · 2026Pooled it
- Pooled it
- Efficacy and safety of ketogenic diet in glioblastoma: an updated systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- Metabolic Therapy in Glioblastoma-Mapping the Evidence for Ketogenic Diet as an Adjunctive Strategy.Nutrients · 2026Review
- Enhanced lipid metabolism serves as a metabolic vulnerability to polyunsaturated fatty acids in glioblastoma.JCI insight · 2026Article
- Nutritional strategies in the management of diffuse gliomas: A systematic review.Neuro-oncology practice · 2025Article
- Targeting the Mitochondria in High-Grade Gliomas.Cancers · 2025Review
- Proteomic Analysis Uncovers Enhanced Inflammatory Phenotype and Distinct Metabolic Changes in IDH1 Mutant Glioma Cells.International journal of molecular sciences · 2025Article
- A phase 1 safety and feasibility trial of a ketogenic diet plus standard of care for patients with recently diagnosed glioblastoma.Scientific reports · 2025Article
- Inhibition of 6-phosphogluconate dehydrogenase suppresses esophageal squamous cell carcinoma growth and enhances the anti-tumor effects of metformin via the AMPK/mTOR pathway.Molecular cancer · 2025Article
- Metformin and glioma: Targeting metabolic dysregulation for enhanced therapeutic outcomes.Translational oncology · 2025Review
- Comprehensive Overview of Ketone Bodies in Cancer Metabolism: Mechanisms and Application.Biomedicines · 2025Review
- Towards Effective Treatment of Glioblastoma: The Role of Combination Therapies and the Potential of Phytotherapy and Micotherapy.Current issues in molecular biology · 2024Review
- Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma.BMC medicine · 2024Review
- Quantification of the Most Effective X-Ray Dosage for Inhibiting Invasion of Glioma Cell Line.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Targeting Mitochondria in Glioma: New Hopes for a Cure.Biomedicines · 2024Review
- Systematic Review and Clinical Insights: The Role of the Ketogenic Diet in Managing Glioblastoma in Cancer Neuroscience.Journal of personalized medicine · 2024Review
- Dietary Influence on Drug Efficacy: A Comprehensive Review of Ketogenic Diet-Pharmacotherapy Interactions.Nutrients · 2024Review
- Metabolic adaptation of myeloid cells in the glioblastoma microenvironment.Frontiers in immunology · 2024Review
- Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAnimal brain-tumor models have demonstrated a synergistic interaction between radiation therapy and a ketogenic diet (KD). Metformin has in-vitro anti-cancer activity, through AMPK activation and mTOR inhibition. We hypothesized that the metabolic stress induced by a KD combined with metformin would enhance radiation's efficacy. We sought to assess the tolerability and feasibility of this approach.
methodsA single-institution phase I clinical trial. Radiotherapy was either 60 or 35 Gy over 6 or 2 weeks, for newly diagnosed and recurrent gliomas, respectively. The dietary intervention consisted of a Modified Atkins Diet (ModAD) supplemented with medium chain triglycerides (MCT). There were three cohorts: Dietary intervention alone, and dietary intervention combined with low-dose or high-dose metformin; all patients received radiotherapy. Factors associated with blood ketone levels were investigated using a mixed-model analysis.
resultsA total of 13 patients were accrued, median age 61 years, of whom six had newly diagnosed and seven with recurrent disease. All completed radiation therapy; five patients stopped the metabolic intervention early. Metformin 850 mg three-times daily was poorly tolerated. There were no serious adverse events. Ketone levels were associated with dietary factors (ketogenic ratio, p < 0.001), use of metformin (p = 0. 02) and low insulin levels (p = 0.002). Median progression free survival was ten and four months for newly diagnosed and recurrent disease, respectively.
conclusionsThe intervention was well tolerated. Higher serum ketone levels were associated with both dietary intake and metformin use. The recommended phase II dose is eight weeks of a ModAD combined with 850 mg metformin twice daily.
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Registered trials
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