title: Effects of metformin on clinical outcome in diabetic patients with advanced HCC receiving sorafenib.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Our findings could be the result of increased tumor aggressiveness and resistance to sorafenib in metformin-treated patients.
authors.affiliation: a Department of Medical Oncology , Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Casadei Gardini
authors.affiliation: b Biosciences Laboratory , IRST IRCCS , Meldola , Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Marisi
authors.affiliation: c Unit of Biostatistics and Clinical Trials , IRST IRCCS , Meldola , Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.affiliation: d Department of Medical Oncology , University of Cagliari , Cagliari , Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
authors.affiliation: e Department of Clinical Medical Oncology, AO Ospedali Riuniti , Università Politecnica delle Marche , Ancona , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Faloppi
authors.affiliation: f Medical Oncology Unit , National Cancer Institute 'Giovanni Paolo II' , Bari , Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Silvestris
authors.affiliation: g Department of Oncology , Pisa University Hospital , Pisa , Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Masi
authors.affiliation: g Department of Oncology , Pisa University Hospital , Pisa , Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Vivaldi
authors.affiliation: f Medical Oncology Unit , National Cancer Institute 'Giovanni Paolo II' , Bari , Italy.
authors.forename: Oronzo
authors.initials: O
authors.lastname: Brunetti
authors.affiliation: h Department of Oncology , Degli Infermi Hospital , Faenza , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tamberi
authors.affiliation: i Department of Internal Medicine , Degli Infermi Hospital , Faenza , Italy.
authors.forename: Francesco Giuseppe
authors.initials: FG
authors.lastname: Foschi
authors.affiliation: j Department of Oncology , Infermi Hospital , Rimini , Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Tamburini
authors.affiliation: k Oncology Pharmacy Laboratory , IRST IRCCS , Meldola , Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tenti
authors.affiliation: l Unit of Gastroenterology , Morgagni-Pierantoni Hospital , Forli , Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ricca Rosellini
authors.affiliation: b Biosciences Laboratory , IRST IRCCS , Meldola , Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ulivi
authors.affiliation: e Department of Clinical Medical Oncology, AO Ospedali Riuniti , Università Politecnica delle Marche , Ancona , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: c Unit of Biostatistics and Clinical Trials , IRST IRCCS , Meldola , Italy.
authors.forename: Oriana
authors.initials: O
authors.lastname: Nanni
authors.affiliation: a Department of Medical Oncology , Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS , Meldola , Italy.
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Frassineti
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy*; D008687:Metformin / Q000627:therapeutic use*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077157:Sorafenib; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D008687:Metformin; D000077157:Sorafenib
keywords: diabetes; hepatocellular carcinoma; insulin; metformin; sorafenib