Is it Time to Test Metformin in Breast Cancer Clinical Trials?
Is it Time to Test Metformin in Breast Cancer Clinical Trials?
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DOI：
10.1158/1055-9965.epi-08-0871
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发表时间：
2009-03-01
影响因子：
3.8
通讯作者：
Decensi, Andrea
中科院分区：
文献类型：
--
作者：
Cazzaniga, Massimiliano;Bonanni, Bernardo;Decensi, Andrea
几项研究已经确定了2型糖尿病患者患癌症的风险增加，这与胰岛素水平升高可能促进癌症的假设一致。因此，人们对探索降低胰岛素水平的抗糖尿病治疗可以降低癌症发病率或癌症相关死亡率的可能性非常感兴趣。最近的观察性研究表明，二甲双胍是一种口服安全且耐受性良好的胰岛素增敏剂降糖药物，与降低癌症风险相关。最近，几项临床前研究评估了二甲双胍在裸鼠体内的作用，并显示乳腺上皮细胞增殖和蛋白质合成均显著减少。在临床环境中的进一步研究得到了迄今为止所获得的有希望的结果的充分支持。在欧洲肿瘤研究所，癌症预防和遗传学部门正计划进行一项临床试验，以评估二甲双胍对接受手术的乳腺癌患者肿瘤细胞增殖的活性。这将是一项术前随机、双盲、安慰剂对照的II期生物标志物试验：100例经组织学证实的乳腺癌患者将被随机分配至二甲双胍（850 mg，每日两次）或安慰剂组，持续28 + 7天，直至手术，以评估药物对肿瘤增殖的活性（通过Ki-67测量）。确认二甲双胍对癌细胞增殖的疗效可能会导致更大的化学预防临床试验。（癌症流行病学生物标志物Prev 2009;18（3）：701-5）
Several studies have identified an increased risk of cancer in type 2 diabetic patients and this is in accordance with the hypothesis that increased insulin levels might promote cancer. Thus, there is a great interest in exploring the possibility that antidiabetic therapies lowering insulin levels could decrease cancer incidence or cancer-related mortality. Recent observational studies have shown that metformin, an oral safe and well-tolerated insulin-sensitizer antidiabetic drug, has been associated with reduced cancer risk. Recently, several preclinical studies have evaluated the effect of metformin in vivo on nude mice and showed a significant reduction of both breast epithelial cell proliferation and protein synthesis. Further investigations in the clinical setting are well-supported by the promising results obtained thus far. At the European Institute of Oncology, the Division of Cancer Prevention and Genetics is planning to conduct a clinical trial to evaluate the activity of metformin on tumor cell proliferation in breast cancer patients undergoing surgery. It will be a presurgical randomized, double blind, placebo-controlled phase II biomarker trial: 100 histologically confirmed breast cancer patients will be randomly assigned to metformin (850 mg twice/daily) or placebo for 28 + 7 days till surgery to assess drug activity on tumor proliferation, as measured by Ki-67. The confirmation of the efficacy of metformin on cancer cell proliferation may lead the way to larger chemoprevention clinical trials. (Cancer Epidemiol Biomarkers Prev 2009;18(3):701-5)