Henderson DeAnna, Frieson Danielle, Zuber Jeffrey, Solomon Solomon S
Endocrinology Division, University of Tennessee Health Science Center, Memphis, Tennessee.
Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
Am J Med Sci. 2017 Sep;354(3):246-251. doi: 10.1016/j.amjms.2017.05.006. Epub 2017 May 19.
Metformin (MF), a diabetic drug, has antineoplastic activity as adjuvant therapy for breast cancer and prostate cancer. MF is thought to work via inhibition of mammalian target of rapamycin and activation of p53 and liver kinase B1 via adenosine 5'-monophosphate-activated protein kinase. We investigated survival, recurrences and metastasis in patients with type 2 diabetes mellitus (DM2) along with colorectal cancer (CC) or lung cancer (LC) taking MF using the electronic medical record in Memphis Veterans Affairs Medical Center (colon, n = 202; lung, n = 180).
Patients with CC or LC and DM2 on MF were compared to controls taking any medication except MF. Recurrences, metastases, secondary cancers, survival and carcinoembryonic antigen levels were compared using t test and chi-squared test. Inclusion criteria were based on MF use, CC or LC diagnosis and DM2.
For CC, the MF group noted fewer deaths (48% versus 76%, P < 0.001), recurrences (4% versus 19%, P = 0.002), metastases (23% versus 46%, P = 0.001), better 5-year survival rates (57% versus 37%, P = 0.004), overall survival years (5.7 versus 4.1, P = 0.007) and greater carcinoembryonic antigen decrease (72% versus 47%, P = 0.015). MF was associated with improved 5-year survival rates (29% versus 15%, P = 0.023) and overall survival years (3.4 versus 1.8, P < 0.001) in LC.
Our study shows that MF therapy is associated with significantly better prognosis in patients with CC and improved survival in LC. Patients with CC on MF had fewer recurrences and metastases. Differences in metabolic pathways between CC and LC likely account for the differences in the effect of MF.
二甲双胍(MF)作为一种糖尿病药物,在乳腺癌和前列腺癌的辅助治疗中具有抗肿瘤活性。MF被认为是通过抑制雷帕霉素哺乳动物靶点,并通过5'-单磷酸腺苷激活蛋白激酶激活p53和肝激酶B1来发挥作用。我们利用孟菲斯退伍军人事务医疗中心的电子病历,调查了2型糖尿病(DM2)合并结直肠癌(CC)或肺癌(LC)且服用MF的患者的生存率、复发率和转移情况(结直肠癌患者202例,肺癌患者180例)。
将CC或LC合并DM2且服用MF的患者与服用除MF以外任何药物的对照组进行比较。使用t检验和卡方检验比较复发率、转移率、继发性癌症、生存率和癌胚抗原水平。纳入标准基于MF的使用、CC或LC诊断以及DM2。
对于CC,MF组的死亡人数较少(48%对76%,P<0.001),复发率较低(4%对19%,P=0.002),转移率较低(23%对46%,P=0.001),5年生存率更高(57%对37%,P=0.004),总生存年数更多(5.7对4.1,P=0.007),癌胚抗原下降幅度更大(72%对47%,P=0.015)。在LC中,MF与5年生存率提高(29%对15%,P=0.023)和总生存年数增加(3.4对1.8,P<0.001)相关。
我们的研究表明,MF治疗与CC患者显著更好的预后相关,且可提高LC患者的生存率。服用MF的CC患者复发和转移较少。CC和LC之间代谢途径的差异可能是MF疗效差异的原因。