近日,发表在Obstet Gynecol 杂志上的一篇有关卵巢癌结果的综述"Relationship of Type II Diabetes and Metformin Use to Ovarian Cancer Progression, Survival, and Chemosensitivity"发现,糖尿病妇女如果服用二甲双胍,其生存期会延长,对于无进展生存期,服用二甲双胍的糖尿病妇女要比根本没有糖尿病的妇女还要好,
Iris L. Romero博士等讲到,他们的研究发现从流行病学到临床研究等方面为二甲双胍的抗肿瘤作用提供越来越多的证据。存在一个生物学机制通过AMPK(磷酸腺苷活化蛋白激酶)激活和一直胰岛素信号,来介导二甲双胍的抗癌作用。
研究小组查看了341名I~IV期卵巢上皮癌(n=273)、输卵管癌(n=34)和腹膜癌(n=34)患者的数据,时间是1992~2010年。队列中包含16名使用二甲双胍的糖尿病患者,28名没有使用。
不管是否患有糖尿病,这些妇女接受相同的方法治疗卵巢癌。各组间手术后小于1cm的残余肿瘤行细胞减灭术比例,使用的化疗类型,化疗周期相似。几乎所有的妇女(95%)都接受基于铂类和紫衫类为基础的化疗,最常用的是卡铂和紫杉醇。
该研究报告认为,使用二甲双胍的糖尿病患者5年无进展生存率为51%,没使用二甲双胍的糖尿病病人为8%,非糖尿病患者为23%(p=0.03)。使用二甲双胍的5年总体存活率为63%,未使用二甲双胍的是23%,非糖尿病组为37%(p=0.03)。控制了“标准临床病理参数”后,二甲双胍的使用与无进展生存率显著相关,但是和总体生存率无相关性。
调整了混杂因素后的生存分析中,比较使用vs未使用二甲双胍的糖尿病患者,前者的疾病复发风险显著降低(HR,0.38)。二甲双胍组死亡风险也降低(HR,0.43),但差异未达到统计学差异。与非糖尿病组相比,使用二甲双胍组的疾病复发和死亡率也降低,但是无统计学差异。没有使用二甲双胍的糖尿病患者相比无糖尿病患者,癌症复发风险(HR,1.42)和死于疾病的风险(HR,1.33)要升高。
研究者注意到,其他研究也表明二甲双胍在多种癌症中都具有抗肿瘤作用,包括乳腺癌、前列腺癌、结肠癌和卵巢癌。临床和实验室研究也表明,二甲双胍可以提高病人对化疗的反应。目前的研究来看,二甲双胍使用者对化疗的反应最好。
但是本研究是回顾性研究,应该考虑到结果是假设产生的,推广到临床实践还有些困难。(生物谷Bioon.com)
doi:10.1097/AOG.0b013e3182393ab3
PMC:
PMID:
Relationship of Type II Diabetes and Metformin Use to Ovarian Cancer Progression, Survival, and Chemosensitivity
Romero, Iris L. MD, MS; McCormick, Anna MD, DO; McEwen, Kelsey A. BS; Park, SeoYoung PhD; Karrison, Theodore PhD; Yamada, S. Diane MD; Pannain, Silvana MD; Lengyel, Ernst MD, PhD
OBJECTIVE: To estimate whether metformin use by ovarian cancer patients with type II diabetes was associated with improved survival.
METHODS: We reviewed the effect of diabetes and diabetes medications on ovarian cancer treatment and outcomes in a single-institution retrospective cohort. Inclusion criteria were International Federation of Gynecology and Obstetrics stage I–IV epithelial ovarian, fallopian, or peritoneal cancer. Exclusion criteria were noninvasive pathology or nonepithelial malignancies. The primary exposures analyzed were history of type II diabetes and diabetes medications. The primary outcomes were progression-free and overall ovarian cancer survival.
RESULTS: Of the 341 ovarian cancer patients included in the study, 297 did not have diabetes, 28 were type II diabetic patients who did not use metformin, and 16 were type II diabetic patients who used metformin. The progression-free survival at 5 years was 51% for diabetic patients who used metformin compared with 23% for the nondiabetic patients and 8% for the diabetic patients who did not use metformin (P=.03). The overall survival at 5 years was 63%, 37%, and 23% for the diabetic patients who used metformin, the nondiabetic patients, and the diabetic patients who did not use metformin, respectively (P=.03). The patients with diabetes received the same treatment for ovarian cancer as the patients without diabetes. The association of metformin use and increased progression-free survival, but not overall survival, remained significant after controlling for standard clinicopathologic parameters.
CONCLUSION: In this ovarian cancer cohort, the patients with type II diabetes who used metformin had longer progression-free survival, despite receiving similar treatment for ovarian cancer.