ArticleCancer2020
Phase 1 dose-finding study of metformin in combination with concurrent cisplatin and radiotherapy in patients with locally advanced head and neck squamous cell cancer.
Article in Cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Acquired BRAFi Resistance Increases Melanoma Cell Sensitivity to Metabolic Targeting with Metformin.International journal of molecular sciences · 2026Article
- Investigation of metformin analogues in targeting signaling molecules of head and neck cancer pathways by computational approaches.Scientific reports · 2026Article
- Metformin-induced xerostomia and chapped lips in a 56-year-old patient with early-stage diabetes: a case report.Journal of medical case reports · 2026Article
- CXCR2 affects sensitization of radioresistant HPV-negative head and neck squamous cell carcinoma cells by ABT-263.Radiation oncology (London, England) · 2026Article
- The significance of mitochondrial DNA changes during the onset and progression of head and neck squamous cell carcinoma.Future oncology (London, England) · 2026Review
- Neoadjuvant immunotherapy in squamous cell carcinoma of the head and neck: current evidence and future perspectives.Molecular cancer · 2025Review
- Effect of metformin on hypoxia-associated gene expression in oral cavity squamous cell carcinoma in non-diabetic patients - a prospective window of opportunity study.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Article
- Identification and validation of hub genes for kidney renal clear cell carcinoma treated with metformin and everolimus combination therapy.Translational cancer research · 2025Article
- Establishment of a chemoresistant laryngeal cancer cell model to study chemoresistance and chemosensitization responses via transcriptomic analysis and a tumor-on-a-chip platform.Bioengineering & translational medicine · 2025Article
- The interplay between DNA damage response and mitochondrial dysfunction in radiotherapy.Frontiers in oncology · 2025Review
- Beneficial Effect of Metformin on the Five-Year Survival in about 40,000 Patients with Head and Neck Cancer.Cancers · 2024Article
- Preventive and Therapeutic Effect of Metformin in Head and Neck Cancer: A Concise Review.Journal of clinical medicine · 2023Review
- Metformin promotes cGAS/STING signaling pathway activation by blocking AKT phosphorylation in gastric cancer.Heliyon · 2023Article
- Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing.Journal of translational medicine · 2023Review
- Combination Therapy as a Promising Way to Fight Oral Cancer.Pharmaceutics · 2023Review
- Is it still worth pursuing the repurposing of metformin as a cancer therapeutic?British journal of cancer · 2023Review
- Metformin increases natural killer cell functions in head and neck squamous cell carcinoma through CXCL1 inhibition.Journal for immunotherapy of cancer · 2022Article
- Integrating Genetic Alterations and the Hippo Pathway in Head and Neck Squamous Cell Carcinoma for Future Precision Medicine.Journal of personalized medicine · 2022Review
- Metformin with Temozolomide for Newly Diagnosed Glioblastoma: Results of Phase I Study and a Brief Review of Relevant Studies.Cancers · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe 5-year overall survival (OS) rate remains at 50% for patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC), thereby underscoring the need for improved treatments. An antidiabetic agent, metformin, was found in retrospective studies to improve survival in patients with HNSCC. Therefore, the authors conducted a phase 1 dose escalation study combining metformin with chemoradiotherapy in patients with LAHNSCC.
methodsNondiabetic patients with LAHNSCC were enrolled in the current study to receive escalating doses of metformin and CRT based on the modified toxicity probability interval design. Metformin cohort doses included 2000 mg, 2550 mg, and 3000 mg daily in divided doses in addition to cisplatin (at a dose of 100 mg/m
resultsTwenty patients were enrolled, 2 of whom withdrew consent. The median age of the patients was 56 years and the majority were male (83%), were white (88%), had p16-positive disease (72%), and were tobacco users (61%). The median length of metformin exposure was 28.5 days. The most common grade ≥3 toxicities were nausea (11%), vomiting (11%), mucositis (6%), acute kidney injury (17%), anemia (6%), and leukopenia (11%). Dose-limiting toxicities included diarrhea and acute kidney injury. After a median follow-up of 19 months, the 2-year overall survival and progression-free survival rates were 90% and 84%, respectively. No hypoglycemia events or lactic acidosis were observed. Cisplatin administration did not appear to affect metformin pharmacokinetics. The maximum tolerated dose for metformin could not be determined given the limited number of patients who tolerated metformin during chemoradiotherapy.
conclusionsTo the authors' knowledge, the current study is the first phase 1 trial combining metformin with chemoradiotherapy. Rates of overall survival and progression-free survival were encouraging in this limited patient population, and warrant further investigation in a phase 2 trial.
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