Andrea Casadei Gardini1, Giorgia Marisi2, Emanuela Scarpi3, Mario Scartozzi4, Luca Faloppi5, Nicola Silvestris6, Gianluca Masi7, Caterina Vivaldi7, Oronzo Brunetti6, Stefano Tamberi8, Francesco Giuseppe Foschi9, Emiliano Tamburini10, Elena Tenti11, Salvatore Ricca Rosellini12, Paola Ulivi2, Stefano Cascinu5, Oriana Nanni3, Giovanni Luca Frassineti1. 1. a Department of Medical Oncology , Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS , Meldola , Italy. 2. b Biosciences Laboratory , IRST IRCCS , Meldola , Italy. 3. c Unit of Biostatistics and Clinical Trials , IRST IRCCS , Meldola , Italy. 4. d Department of Medical Oncology , University of Cagliari , Cagliari , Italy. 5. e Department of Clinical Medical Oncology, AO Ospedali Riuniti , Università Politecnica delle Marche , Ancona , Italy. 6. f Medical Oncology Unit , National Cancer Institute 'Giovanni Paolo II' , Bari , Italy. 7. g Department of Oncology , Pisa University Hospital , Pisa , Italy. 8. h Department of Oncology , Degli Infermi Hospital , Faenza , Italy. 9. i Department of Internal Medicine , Degli Infermi Hospital , Faenza , Italy. 10. j Department of Oncology , Infermi Hospital , Rimini , Italy. 11. k Oncology Pharmacy Laboratory , IRST IRCCS , Meldola , Italy. 12. l Unit of Gastroenterology , Morgagni-Pierantoni Hospital , Forli , Italy.
Abstract
BACKGROUND AND 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.
BACKGROUND AND 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 cirrhoticpatients 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.