ArticleCancer2019
Phase 1 lead-in to a phase 2 factorial study of temozolomide plus memantine, mefloquine, and metformin as postradiation adjuvant therapy for newly diagnosed glioblastoma.
Article in Cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers, 1 of them a synthesis 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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Enhancing radiation sensitivity in malignant brain tumors with chloroquine: a systematic review.Journal of neuro-oncology · 2025Pooled it
- Fatty Acid Metabolism Rewires Glioblastoma Progression and Treg-Mediated Immune Resistance.Cancers · 2026Review
- Glutamate Drives Glioblastoma Invasion in Three-Dimensional Hyaluronic Acid Hydrogels.Tissue engineering. Part A · 2026Article
- Targeting the Mitochondria in High-Grade Gliomas.Cancers · 2025Review
- Phenotypic variations in glioma stem cells: regulatory mechanisms and implications for therapeutic strategies.Journal of translational medicine · 2025Review
- Glucose and antidiabetic therapy in temozolomide resistance in glioblastoma.World journal of clinical oncology · 2025Review
- Metformin and glioma: Targeting metabolic dysregulation for enhanced therapeutic outcomes.Translational oncology · 2025Review
- Article
- Structure-activity relationships study ofFuture medicinal chemistry · 2024Article
- Metabolic adaptation of myeloid cells in the glioblastoma microenvironment.Frontiers in immunology · 2024Review
- NMDAR antagonists suppress tumor progression by regulating tumor-associated macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- From signalling pathways to targeted therapies: unravelling glioblastoma's secrets and harnessing two decades of progress.Signal transduction and targeted therapy · 2023Review
- Could Metformin and Resveratrol Support Glioblastoma Treatment? A Mechanistic View at the Cellular Level.Cancers · 2023Review
- NMDA receptor signaling induces the chemoresistance of temozolomide via upregulation of MGMT expression in glioblastoma cells.Journal of neuro-oncology · 2022Article
- The Next Frontier in Health Disparities-A Closer Look at Exploring Sex Differences in Glioma Data and Omics Analysis, from Bench to Bedside and Back.Biomolecules · 2022Review
- Metformin with Temozolomide for Newly Diagnosed Glioblastoma: Results of Phase I Study and a Brief Review of Relevant Studies.Cancers · 2022Article
- Neurotransmitters: Potential Targets in Glioblastoma.Cancers · 2022Review
- Targeting Glioblastoma Stem Cells to Overcome Chemoresistance: An Overview of Current Therapeutic Strategies.Biomedicines · 2022Review
- Does memantine show chemopreventive effect against mice 4T1 breast tumor model?Turkish journal of medical sciences · 2022Article
- Review
Corrections and comments
- Commented on by
- Commented on by
- Erratum issuedErrata.2019
Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRepurposed memantine, mefloquine, and metformin have putative anticancer activity. The objective of this phase 1 study was to determine the maximum tolerated doses (MTDs) of combinations of these agents with temozolomide (TMZ).
methodsAdults with newly diagnosed glioblastoma who completed chemoradiation were eligible. The patients were assigned to receive doublet, triplet, or quadruplet therapy with TMZ combined with mefloquine, memantine, and/or metformin. Dose-limiting toxicities (DLTs) were determined, using a 3 + 3 study design.
resultsOf 85 enrolled patients, 4 did not complete cycle 1 (the DLT observation period) for nontoxicity reasons, and 81 were evaluable for DLT. The MTDs for doublet therapy were memantine 20 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 850 mg twice daily. For triplet therapy, the MTDs were memantine 10 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 850 mg twice daily. For quadruplet therapy, the MTDs were memantine 10 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 500 mg twice daily. DLTs included dizziness (memantine) and gastrointestinal effects (metformin). Lymphopenia was the most common adverse event (66%). From study entry, the median survival was 21 months, and the 2-year survival rate was 43%.
conclusionsMemantine, mefloquine, and metformin can be combined safely with TMZ in patients with newly diagnosed glioblastoma.
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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.