Luo Xiaofeng, Chen Xi, Wang Lin, Yang Bowen, Cai Shuang
Department of Pharmacy, The First Hospital of China Medical University, Shenyang, China.
School of Pharmacy, China Medical University, Shenyang, China.
Front Pharmacol. 2021 Jun 3;12:639016. doi: 10.3389/fphar.2021.639016. eCollection 2021.
Resistance to anticancer agents ensures a poor prognosis in patients with lung cancer. Metformin could enhance the anticancer effects of standard antineoplastic agents [traditional chemotherapy drugs, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), or immune checkpoint inhibitors (ICIs)]; however, it is unclear whether metformin can be combined with antineoplastic agents in the treatment of lung cancer. To explore the efficacy of combinational strategies, we performed a systematic review and meta-analysis for diabetic and non-diabetic patients with lung cancer. An electronic literature search was performed to obtain relevant randomized controlled trials (RCTs) and observational cohort studies. Hazard ratios (HR) with 95% confidence intervals (CI) of overall survival (OS) and progression-free survival (PFS) outcomes were extracted. Subgroup analysis by antineoplastic agents, study type, histology and clinical stage were investigated. 14 studies (three RCTs and eleven observational cohort studies) consisting 3,856 patients were included in the meta-analysis. Compared to standard antineoplastic agents alone (traditional chemotherapy drugs, EGFR-TKIs or ICIs), the antineoplastic agents combined with metformin significantly improved OS (HR 0.73, 95% CI 0.66-0.81, < 0.00001) and PFS (HR 0.72, 95% CI 0.59-0.88, = 0.001); a similar association was found in observational evidence. Limited data from RCTs showed no differences in OS or PFS. Metformin plus antineoplastic agents may improve survival outcomes of patients with lung cancer. Further investigation is needed.
对抗癌药物产生耐药性会导致肺癌患者预后不良。二甲双胍可增强标准抗肿瘤药物（传统化疗药物、表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）或免疫检查点抑制剂（ICIs））的抗癌效果；然而，二甲双胍能否与抗肿瘤药物联合用于肺癌治疗尚不清楚。为了探究联合治疗策略的疗效，我们对糖尿病和非糖尿病肺癌患者进行了一项系统评价和荟萃分析。通过电子文献检索获取相关的随机对照试验（RCTs）和观察性队列研究。提取总生存期（OS）和无进展生存期（PFS）结果的风险比（HR）及95%置信区间（CI）。对抗肿瘤药物、研究类型、组织学和临床分期进行亚组分析。荟萃分析纳入了14项研究（3项RCTs和11项观察性队列研究），共3856例患者。与单独使用标准抗肿瘤药物（传统化疗药物、EGFR-TKIs或ICIs）相比，抗肿瘤药物联合二甲双胍显著改善了总生存期（HR 0.73，95%CI 0.66-0.81，<0.00001）和无进展生存期（HR 0.72，95%CI 0.59-0.88，=0.001）；观察性证据中也发现了类似的关联。来自RCTs的有限数据显示总生存期或无进展生存期无差异。二甲双胍联合抗肿瘤药物可能改善肺癌患者的生存结局。还需要进一步研究。
