Glasberg João, Talans Aley, Giollo Thomás Rivelli, Recchimuzzi Débora Zachello, Neto João Evangelista Bezerra, Lopez Rossana Veronica Mendonza, Hoff Paulo Marcelo Gehm, Riechelmann Rachel P
Department of Clinical Oncology, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo - FMUSP, São Paulo, Brazil.
Post Graduate Program, Faculdade de Medicina da Universidade de São Paulo, Brazil.
Ecancermedicalscience. 2022 Mar 31;16:1369. doi: 10.3332/ecancer.2022.1369. eCollection 2022.
Preclinical studies have suggested that metformin has anti-tumour effects, likely due to blockage of mammalian target of rapamycin pathway through adenosine monophosphate-activated protein kinase and decreased insulin levels. A retrospective study showed that metformin added to everolimus to treat type 2 diabetes mellitus offered longer progression-free survival (PFS) in patients with pancreatic neuroendocrine tumours (NET).
To evaluate the efficacy and safety of metformin monotherapy in patients with advanced/metastatic well-differentiated NET (WD-NET) of gastroenteropancreatic (GEP) or pulmonary origin.
Single-arm phase II trial of metformin 850 mg PO twice daily until progression or intolerance for patients with progressive metastatic well-differentiated GEP or pulmonary NET. The primary endpoint was disease control rate (DCR) by RECIST 1.1 at 6 months. Secondary endpoints were response rate, PFS, toxicity and variations in glycaemic profiles (glycaemia, glycated haemoglobin and peptide C and insulin) at baseline, at 30 and 90 days.
From 2014 to 2019, 28 patients were enrolled: median age was 50 years; 84% had non-functional NET, 86% were of GEP origin and 62% had G2 NET. At the time of last follow-up, 26 patients had progression, with 13 (46%) presenting DCR at 6 months and a median PFS of 6.3 months (95% confidence interval: 3.2-9.3). There was no objective response, but one patient with refractory carcinoid syndrome had complete symptom relief, lasting for more than 5 years. Variations in glycaemic profiles were not associated with DCR at 6 months. Diarrhoea was the most common adverse event, being grade 3 or 4 in 10% of the cases.
Metformin monotherapy offers modest anti-tumour activity in well-differentiated GEP or lung NET.
临床前研究表明，二甲双胍具有抗肿瘤作用，这可能是由于通过单磷酸腺苷激活的蛋白激酶阻断雷帕霉素哺乳动物靶点通路以及降低胰岛素水平所致。一项回顾性研究显示，在依维莫司基础上加用二甲双胍治疗2型糖尿病，可使胰腺神经内分泌肿瘤（NET）患者获得更长的无进展生存期（PFS）。
评估二甲双胍单药治疗胃肠道胰腺（GEP）或肺部来源的晚期/转移性高分化NET（WD-NET）患者的疗效和安全性。
对转移性高分化GEP或肺部NET患者进行单臂II期试验，口服二甲双胍850 mg，每日两次，直至病情进展或出现不耐受。主要终点为6个月时根据RECIST 1.1标准评估的疾病控制率（DCR）。次要终点为缓解率、PFS、毒性以及基线、30天和90天时血糖谱（血糖、糖化血红蛋白、肽C和胰岛素）的变化。
2014年至2019年，共纳入28例患者：中位年龄为50岁；84%为无功能性NET，86%为GEP来源，62%为G2 NET。在末次随访时，26例患者病情进展，其中13例（46%）在6个月时达到DCR，中位PFS为6.3个月（95%置信区间：3.2 - 9.3）。未观察到客观缓解，但1例难治性类癌综合征患者症状完全缓解，持续超过5年。血糖谱变化与6个月时的DCR无关。腹泻是最常见的不良事件，10%的病例为3级或4级。
二甲双胍单药治疗在高分化GEP或肺部NET中具有适度的抗肿瘤活性。
Zotero 插件
