Metanalyses on metformin's role in pancreatic cancer suffer from severe bias and low data quality – An umbrella review

Nowicka, Zuzanna; Matyjek, Anna; Płoszka, Katarzyna; Łaszczych, Mateusz; Fendler, Wojciech

doi:10.1016/j.pan.2023.01.007

Cited by 5 publications

(2 citation statements)

References 26 publications

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“…The poor prognosis of pancreatic cancer (PanC) makes it the seventh biggest killer worldwide [ 111 , 112 ]. It has been suggested that PPARγ may be a prognostic marker for pancreatic ductal adenocarcinoma [ 113 ].…”

Section: Resultsmentioning

confidence: 99%

Peroxisome proliferator-activated receptors: Key regulators of tumor progression and growth

Asgharzadeh,

Memarzia,

Alikhani

et al. 2024

Translational Oncology

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Section: Resultsmentioning

confidence: 99%

Peroxisome proliferator-activated receptors: Key regulators of tumor progression and growth

Asgharzadeh,

Memarzia,

Alikhani

et al. 2024

Translational Oncology

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“…The inhibitory effect of metformin via activated AMPK suggests that metformin is a potential therapeutic agent in cancer. Randomized controlled trials have reported the clinical effects of metformin on the survival prognosis of patients with lung and pancreatic cancer [ 12 , 13 ]. However, only a few trials have reported a benefit of add-on metformin to standard therapy due to inadequate dosages, limitations associated with observational studies, and assessment of patients with advanced disease.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study)

et al. 2023

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Purpose Glioblastoma (GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of metformin in patients with recurrent or refractory GBM treated with low-dose temozolomide. Methods Included patients were randomly assigned to a control group [placebo plus low-dose temozolomide (50 mg/m2, daily)] or an experimental group [metformin (1000 mg, 1500 mg, and 2000 mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose temozolomide]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety. Results Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI 12.19–21.68 months) in the experimental group and 7.69 months (95% CI 5.16–22.67 months) in the control group, showing no significant difference by the log-rank test (HR: 0.78; 95% CI 0.39–1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.4% in the experimental group, respectively. Conclusions Although the metformin plus temozolomide regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM. Trial registration NCT03243851, registered August 4, 2017.

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Synergistic effects of calcium channel blockers and renin-angiotensin inhibitors with gemcitabine-based chemotherapy on the survival of patients with pancreatic cancer

Kraj,

Chmiel,

Śliwczyński

et al. 2024

J Cancer Res Clin Oncol

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Purpose Pancreatic cancer remains a significant public health challenge, with poor long-term outcomes due to the lack of effective treatment options. Repurposing commonly used clinical drugs, such as ACE inhibitors, ARBs, CCBs, and metformin, may enhance the efficacy of chemotherapy and offer a promising therapeutic strategy for improving patient outcomes. Methods A retrospective analysis of concomitant treatment with ACE-Is, ARBs, CCBs, and metformin alongside gemcitabine chemotherapy in patients with pancreatic cancer was conducted. Treatment responses were evaluated, with overall survival (OS) estimated using the Kaplan–Meier method. Additionally, the Cox proportional hazards model was employed to assess the impact of these specific agents on patient survival. Results 4628 patients with various stages of pancreatic cancer were identified in the database between 2007 and 2016. The estimated overall survival (OS) in the analyzed group was 6.9 months (95% CI 6.4–7). The use of any of the analyzed drugs was associated with a significant improvement in mOS of 7.5 months (95% CI 6.8–7.8) vs. 6.7 months (95% CI 6.4–7.0) for patients who did not have additional treatment (p < 0.0001). ARBs, ACE-Is, CCBs, and metformin varied in their effectiveness in prolonging mOS among patients. The longest mOS of 8.9 months (95% CI 7.7–11.6) was observed in patients receiving additional therapy with ARBs, while the shortest mOS of 7.7 months (95% CI 6.5–8.9) was achieved by patients receiving metformin. In the adjusted Cox analysis, metformin was associated with a significantly weaker effect on mOS (p = 0.029). A particularly interesting trend in prolonging 5-year survival was demonstrated by ARBs and CCBs with 14.1% (95% CI 9–22%) and 14.8% (95% CI 11.1–19.6%), respectively, compared to patients not taking these drugs, who achieved a 5-year OS of 3.8% (95% CI 3.2–4.4%). Conclusion Our results demonstrate a significant positive impact of ARBs, ACE inhibitors, and CCBs on survival in patients with pancreatic cancer treated with gemcitabine. The addition of these inexpensive and relatively safe drugs in patients with additional comorbidities may represent a potential therapeutic option in this indication. However, prospective clinical trials to evaluate the optimal patient population and further studies to determine the potential impact of these agents on chemotherapy are necessary.

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Metanalyses on metformin's role in pancreatic cancer suffer from severe bias and low data quality – An umbrella review

Cited by 5 publications

References 26 publications

Peroxisome proliferator-activated receptors: Key regulators of tumor progression and growth

Peroxisome proliferator-activated receptors: Key regulators of tumor progression and growth

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study)

Synergistic effects of calcium channel blockers and renin-angiotensin inhibitors with gemcitabine-based chemotherapy on the survival of patients with pancreatic cancer

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