Tolerability, safety and feasibility of metformin combined with chemoradiotherapy in patients with locally advanced cervical cancer: A phase II, randomized study
Background and purpose: Locally advanced cervical cancer is treated with chemoradiotherapy. The treatment-related morbidity is high. Tumor hypoxia has prognostic impact and represents a valid, interventional target. This phase II study investigated efficacy of the antidiabetic drug metformin to modi...
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Medical Journals Sweden
2025-03-01
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| Series: | Acta Oncologica |
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| Online Access: | https://medicaljournalssweden.se/actaoncologica/article/view/43045 |
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| author | Kjersti Skipar Tord Hompland Kjersti V. Lund Christina S. Fjeldbo Kristina Lindemann Taran P. Hellebust Heidi Lyng Kjersti Bruheim |
| author_facet | Kjersti Skipar Tord Hompland Kjersti V. Lund Christina S. Fjeldbo Kristina Lindemann Taran P. Hellebust Heidi Lyng Kjersti Bruheim |
| author_sort | Kjersti Skipar |
| collection | DOAJ |
| description | Background and purpose: Locally advanced cervical cancer is treated with chemoradiotherapy. The treatment-related morbidity is high. Tumor hypoxia has prognostic impact and represents a valid, interventional target. This phase II study investigated efficacy of the antidiabetic drug metformin to modify hypoxia according to established biomarkers. Preliminary results including tolerability, safety and feasibility are reported here.
Patients and methods: Patients were included in a 1:1 randomized, open-label design, comparing standard chemoradiotherapy ± metformin. Metformin 850 mg twice daily was administered 1 week before and during chemoradiotherapy. Magnetic resonance images (MRI) and tumor biopsies were collected at baseline, after 1 week of metformin treatment, and at brachytherapy for biomarker assessments. Tolerability and safety were determined by treatment completion rates and frequency of adverse events (AEs). Safety was further evaluated by possible increase in MRI-based hypoxia during the first week of metformin. Feasibility was determined by proportion of completed study interventions and imaging and biopsy procedures.
Results: In total, 18 and 23 patients were allocated to the intervention and control arm, respectively. Eighteen and 15 patients completed metformin treatment for 1 and 5 weeks. Frequency of AEs ≥ grade 3 was not significantly different between study arms. Most AEs were gastrointestinal toxicities. Tumors with increase in hypoxia during the first week were all below the defined safety limit. A total of 98% of scheduled MR series and biopsies were collected with satisfactory quality.
Interpretation: Addition of metformin to chemoradiotherapy is tolerable and safe. Serial sampling of MRI and tumor biopsies for hypoxia biomarker assessment is feasible.
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| format | Article |
| id | doaj-art-b863daddff5547ca8f2e8f7b4106d601 |
| institution | Kabale University |
| issn | 1651-226X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Medical Journals Sweden |
| record_format | Article |
| series | Acta Oncologica |
| spelling | doaj-art-b863daddff5547ca8f2e8f7b4106d6012025-08-20T03:41:46ZengMedical Journals SwedenActa Oncologica1651-226X2025-03-016410.2340/1651-226X.2025.43045Tolerability, safety and feasibility of metformin combined with chemoradiotherapy in patients with locally advanced cervical cancer: A phase II, randomized studyKjersti Skipar0Tord Hompland1Kjersti V. Lund2Christina S. Fjeldbo3Kristina Lindemann4Taran P. Hellebust5Heidi Lyng6Kjersti Bruheim7Department of Oncology, Telemark Hospital Trust, Skien, Norway; Department of Radiation Biology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Radiation Biology, Oslo University Hospital, Oslo, NorwayDepartment of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, NorwayDepartment of Radiation Biology, Oslo University Hospital, Oslo, NorwayDepartment of Surgical Oncology, Section for gynecological oncology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Medical Physics, Oslo University Hospital, Oslo, NorwayDepartment of Radiation Biology, Oslo University Hospital, Oslo, Norway; Department of Physics, University of Oslo, Oslo, NorwayDepartment of Oncology, Oslo University Hospital, Oslo, NorwayBackground and purpose: Locally advanced cervical cancer is treated with chemoradiotherapy. The treatment-related morbidity is high. Tumor hypoxia has prognostic impact and represents a valid, interventional target. This phase II study investigated efficacy of the antidiabetic drug metformin to modify hypoxia according to established biomarkers. Preliminary results including tolerability, safety and feasibility are reported here. Patients and methods: Patients were included in a 1:1 randomized, open-label design, comparing standard chemoradiotherapy ± metformin. Metformin 850 mg twice daily was administered 1 week before and during chemoradiotherapy. Magnetic resonance images (MRI) and tumor biopsies were collected at baseline, after 1 week of metformin treatment, and at brachytherapy for biomarker assessments. Tolerability and safety were determined by treatment completion rates and frequency of adverse events (AEs). Safety was further evaluated by possible increase in MRI-based hypoxia during the first week of metformin. Feasibility was determined by proportion of completed study interventions and imaging and biopsy procedures. Results: In total, 18 and 23 patients were allocated to the intervention and control arm, respectively. Eighteen and 15 patients completed metformin treatment for 1 and 5 weeks. Frequency of AEs ≥ grade 3 was not significantly different between study arms. Most AEs were gastrointestinal toxicities. Tumors with increase in hypoxia during the first week were all below the defined safety limit. A total of 98% of scheduled MR series and biopsies were collected with satisfactory quality. Interpretation: Addition of metformin to chemoradiotherapy is tolerable and safe. Serial sampling of MRI and tumor biopsies for hypoxia biomarker assessment is feasible. https://medicaljournalssweden.se/actaoncologica/article/view/43045cervical cancermultimodal imaginghypoxia biomarkershypoxia modificationmetforminrandomized phase II trial |
| spellingShingle | Kjersti Skipar Tord Hompland Kjersti V. Lund Christina S. Fjeldbo Kristina Lindemann Taran P. Hellebust Heidi Lyng Kjersti Bruheim Tolerability, safety and feasibility of metformin combined with chemoradiotherapy in patients with locally advanced cervical cancer: A phase II, randomized study Acta Oncologica cervical cancer multimodal imaging hypoxia biomarkers hypoxia modification metformin randomized phase II trial |
| title | Tolerability, safety and feasibility of metformin combined with chemoradiotherapy in patients with locally advanced cervical cancer: A phase II, randomized study |
| title_full | Tolerability, safety and feasibility of metformin combined with chemoradiotherapy in patients with locally advanced cervical cancer: A phase II, randomized study |
| title_fullStr | Tolerability, safety and feasibility of metformin combined with chemoradiotherapy in patients with locally advanced cervical cancer: A phase II, randomized study |
| title_full_unstemmed | Tolerability, safety and feasibility of metformin combined with chemoradiotherapy in patients with locally advanced cervical cancer: A phase II, randomized study |
| title_short | Tolerability, safety and feasibility of metformin combined with chemoradiotherapy in patients with locally advanced cervical cancer: A phase II, randomized study |
| title_sort | tolerability safety and feasibility of metformin combined with chemoradiotherapy in patients with locally advanced cervical cancer a phase ii randomized study |
| topic | cervical cancer multimodal imaging hypoxia biomarkers hypoxia modification metformin randomized phase II trial |
| url | https://medicaljournalssweden.se/actaoncologica/article/view/43045 |
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