Casadei Gardini Andrea, Marisi Giorgia, Scarpi Emanuela, Scartozzi Mario, Faloppi Luca, Silvestris Nicola, Masi Gianluca, Vivaldi Caterina, Brunetti Oronzo, Tamberi Stefano, Foschi Francesco Giuseppe, Tamburini Emiliano, Tenti Elena, Ricca Rosellini Salvatore, Ulivi Paola, Cascinu Stefano, Nanni Oriana, Frassineti Giovanni Luca
a Department of Medical Oncology , Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
b Biosciences Laboratory , IRST IRCCS , Meldola , Italy.
Expert Opin Pharmacother. 2015;16(18):2719-25. doi: 10.1517/14656566.2015.1102887. Epub 2015 Oct 29.
Several studies have reported an association between type 2 diabetes mellitus and hepatocellular carcinoma (HCC). Data from several retrospective studies and meta-analyses have highlighted a reduction of about 50% in the risk of developing HCC in cirrhotic patients treated with metformin for diabetes. The aim of this study was to evaluate the different outcomes of patients who received or did not receive metformin during treatment with sorafenib.
We analyzed 93 patients consecutively treated with sorafenib. Forty-two (45.2%) patients were diabetic, of whom 31 were on metformin. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with the log-rank test.
The concomitant use of sorafenib and metformin was associated with a median PFS of 2.6 months (95% CI 1.9-3.3) compared to 5.0 months (95% CI 2.5-8.2) for patients receiving sorafenib alone (p = 0.029). The median OS of patients treated with the combination was 10.4 months (95% CI 3.9-14.4) compared to 15.1 months (95% CI 11.7-17.8) for those who were not given metformin (p = 0.014).
Our findings could be the result of increased tumor aggressiveness and resistance to sorafenib in metformin-treated patients.
多项研究报告了2型糖尿病与肝细胞癌（HCC）之间的关联。多项回顾性研究和荟萃分析的数据强调，使用二甲双胍治疗糖尿病的肝硬化患者发生HCC的风险降低约50%。本研究的目的是评估在索拉非尼治疗期间接受或未接受二甲双胍治疗的患者的不同结局。
我们分析了93例连续接受索拉非尼治疗的患者。42例（45.2%）患者患有糖尿病，其中31例正在服用二甲双胍。采用Kaplan-Meier方法估计无进展生存期（PFS）和总生存期（OS），并通过对数秩检验进行比较。
与单独接受索拉非尼治疗的患者相比，索拉非尼与二甲双胍联合使用的患者中位PFS为2.6个月（95%CI 1.9 - 3.3），而单独接受索拉非尼治疗的患者中位PFS为5.0个月（95%CI 2.5 - 8.2）（p = 0.029）。联合治疗患者的中位OS为10.4个月（95%CI 3.9 - 14.4），未使用二甲双胍的患者中位OS为15.1个月（95%CI 11.7 - 17.8）（p = 0.014）。
我们的研究结果可能是由于接受二甲双胍治疗的患者肿瘤侵袭性增加以及对索拉非尼产生耐药性所致。
