Is Metformin Associated With Improved Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer?

Planellas, Pere; Cornejo, Lídia; Rodríguez-Hermosa, José Ignacio; Maldonado, Eloy; Timoteo, Ander; Hernández-Yagüe, X.; Farrés, Ramón; Codina-Cazador, Antoni

doi:10.1016/j.jss.2021.06.079

Cited by 5 publications

(8 citation statements)

References 34 publications

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“…3 –1). For 244 DM patients treated with metformin versus 1532 nondiabetic patients, the pooled OR was 1.70 ( CI : 0.86–3.36, I 2 = 67%, p = 0.130) [ 9 , 10 , 12 , 13 , 15 ] (Fig. 4 –1).…”

Section: Resultsmentioning

confidence: 99%

Metformin increases pathological responses to rectal cancers with neoadjuvant chemoradiotherapy: a systematic review and meta-analysis

et al. 2023

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Background To summarize the chemo-radio effect of metformin in rectal cancers with neoadjuvant chemoradiotherapy on pathological response, tumor regression grade (TRG), and T/N downstaging. Methods PubMed, MEDLINE, Embase, and Cochrane Database of collected reviews were searched up to June 30, 2022. This study conducted systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sheet. Odds ratios (ORs) and confidence intervals (CIs) which calculated by random-effects models were displayed in forest plots. Newcastle–Ottawa scale was used to assess the risk of bias of the observational cohort studies. Results This systematic review and meta-analysis comprised eight cohorts out of seven studies, with 2294 patients in total. We performed two-way comparison for metformin in diabetic patients vs (1) non-metformin drugs in diabetic patients and (2) nondiabetic patients. In diabetes patient studies, the metformin group had a significantly increased pathological response on TRG (OR: 3.28, CI: 2.01–5.35, I2 = 0%, p < 0.001) and T downstaging (OR: 2.14, CI: 1.24–3.67, I2 = 14%, p = 0.006) in comparison with a non-metformin group. When compared with nondiabetic patients, the pathological response on TRG (OR: 2.67, CI: 1.65–4.32, I2 = 43%, p < 0.001) and T downstaging (OR: 1.96, CI: 1.04–3.71, I2 = 66%, p = 0.04) were also higher in metformin group. The limitation was that no randomized controlled trials were available based on current literature review. Small sample sizes for diabetic metformin or non-metformin users in rectal cancer patients reduced the power of the study. Conclusions For patients with rectal cancer and treated with neoadjuvant chemoradiotherapy, metformin administration in diabetic patients increased the pathological response on tumor-regression grade and T downstaging. Further well-designed, high-quality randomized controlled trials are required to reveal the actual effect of metformin.

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Section: Resultsmentioning

confidence: 99%

Metformin increases pathological responses to rectal cancers with neoadjuvant chemoradiotherapy: a systematic review and meta-analysis

et al. 2023

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“…Based on these observations, many preclinical studies were conducted to determine the clinical usefulness of combined RT and metformin which have had promising results 12 , 16 , 17 . However, the results of clinical studies are still inconsistent 21 , 22 , 25 .…”

Section: Discussionmentioning

confidence: 99%

“…Some of these studies have shown that metformin improves outcomes in patients who received RT for the treatment of various cancers including colorectal cancer 18 – 22 . However, synergistic effects of these two treatment modalities were not always evident 23 – 25 and detailed molecular mechanisms of the synergism are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Metformin combined with local irradiation provokes abscopal effects in a murine rectal cancer model

Tojo

Miyato

Koinuma

et al. 2022

Sci Rep

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Although preoperative chemoradiation therapy can down-stage locally advanced rectal cancer (LARC), it has little effect on distant metastases. Metformin exerts an anti-cancer effect partly through the activation of host immunity. LuM1, a highly lung metastatic subclone of colon 26, was injected subcutaneously (sc) in BALB/c mice and treated with metformin and/or local radiation (RT). Lung metastases and the primary tumors were evaluated and the phenotypes of immune cells in the spleen and lung metastases were examined with flow cytometry and immunohistochemistry. Local RT, but not metformin, partially delayed the growth of sc tumor which was augmented with metformin. Lung metastases were unchanged in metformin or RT alone, but significantly reduced in the combined therapy. The ratios of splenic T cells tended to be low in the RT group, which were increased by the addition of metformin. IFN-γ production of the splenic CD4(+) and CD8(+) T cells was enhanced and CD49b (+) CD335(+) activated NK cells was increased after combined treatment group. Density of NK cells infiltrating in lung metastases was increased after combination treatment. Metformin effectively enhances local and abscopal effects of RT though the activation of cell-mediated immunity and might be clinically useful for LARC.

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“…Based on these observations, many preclinical studies were conducted to determine the clinical usefulness of combined RT and metformin which have had promising results 12,16,17 . However, the results of clinical studies are still inconsistent 21,22,25 .…”

Section: Discussionmentioning

confidence: 99%

“…Some of these studies have shown that metformin improves outcomes in patients who received RT for the treatment of various cancers including colorectal cancer [18][19][20][21][22] . However, synergistic effects of these two treatment modalities were not always evident [23][24][25] and detailed molecular mechanisms of the synergism are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Metformin Combined with Local Irradiation Provokes Abscopal Effects in a Murine Rectal Cancer Model

Tojo

Miyato

Koinuma

et al. 2021

Preprint

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BackgroundAlthough preoperative chemoradiation therapy can down-stage locally advanced rectal cancer (LARC), it has little effect on distant metastases. Metformin exerts an anti-cancer effect partly through the activation of host immunity. MethodLuM1, a highly lung metastatic subclone of colon 26, was injected subcutaneously in BALB/c mice and treated with metformin and/or local radiation (RT). Lung metastases and the primary tumor were evaluated and the phenotypes of immune cells in the spleen and lung metastases were examined with flowcytometry and immunohistochemistry.ResultsLocal RT, but not metformin, partially delayed the growth of sc tumor which was augmented with metformin. Lung metastases was unchanged in metformin or RT alone, but significantly reduce in the combined therapy. The ratios of splenic T cells tended to be low in the RT group, which were increased by the addition of metformin. IFN-gamma production of the splenic CD4(+) and CD8(+) T cells was enhanced and CD49b (+) CD335(+) activated NK cells was increased after combined treatment group. Density of NK cells infiltrating in lung metastases was increased after combination treatment. ConclusionMetformin effectively enhances local and abscopal effects of RT though the activation of cell-mediated immunity and might be clinically useful for LARC.

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Is Metformin Associated With Improved Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer?

Cited by 5 publications

References 34 publications

Metformin increases pathological responses to rectal cancers with neoadjuvant chemoradiotherapy: a systematic review and meta-analysis

Metformin increases pathological responses to rectal cancers with neoadjuvant chemoradiotherapy: a systematic review and meta-analysis

Metformin combined with local irradiation provokes abscopal effects in a murine rectal cancer model

Metformin Combined with Local Irradiation Provokes Abscopal Effects in a Murine Rectal Cancer Model

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