@article{265eb51165124da9b6ca9bf84ee3e7a3,
title = "Impact of Metformin Use and Diabetic Status During Adjuvant Fluoropyrimidine-Oxaliplatin Chemotherapy on the Outcome of Patients with Resected Colon Cancer: A TOSCA Study Subanalysis",
abstract = "Background: Type 2 diabetes mellitus (T2DM) is associated with increased risk of colon cancer (CC), whereas metformin use seems to be protective. However, the impact of metformin use on the risk of death or disease recurrence after radical surgery for CC remains uncertain. Materials and Methods: This is a substudy conducted in patients with high-risk stage II or stage III CC randomized in the TOSCA trial, which compared 3 versus 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy. Objective of the study was to investigate the impact of metformin exposure during adjuvant chemotherapy on overall survival (OS) and relapse-free survival (RFS). We also evaluated the impact of T2DM or metformin dosage on clinical outcomes. Results: Out of 3,759 patients enrolled in the TOSCA trial, 133 patients with diabetes (9.2%) and 1,319 without diabetes (90.8%) were recruited in this study. After excluding 13 patients with diabetes without information on metformin exposure, 76 patients with T2DM (63.3%) were defined as metformin users and 44 (36.7%) as metformin nonusers. After a median follow-up of 60.4 months, 26 (21.7%) patients relapsed and 16 (13.3%) died. Metformin use was neither associated with OS (adjusted hazard ratio [HR], 1.51; 95% confidence interval [CI], 0.48–4.77; p =.4781) nor with RFS (HR, 1.56; 95% CI, 0.69–3.54; p =.2881). Similarly, we found no association between T2DM or metformin dosage and OS or RFS. Conclusions: Metformin use and T2DM did not impact on OS or RFS in patients with resected CC treated with adjuvant fluoropyrimidine-oxaliplatin chemotherapy. Larger studies and longer follow-up are required to clarify the potential efficacy of metformin in improving the prognosis of patients with CC. Implications for Practice: The role of the antidiabetic drug metformin in colon cancer prevention and treatment is highly debated. While low-dose metformin reduced the incidence of colorectal adenomas in two prospective studies, its effect in patients with already established colon cancer remains unclear. In this study, the potential impact of metformin on the survival of resected colon cancer patients who received adjuvant chemotherapy was investigated in the context of the TOSCA study. We did not find any association between metformin use or dosages and patient survival. Prospective studies are required to draw definitive conclusions about metformin impact on colon cancer recurrence and survival. {\textcopyright} AlphaMed Press 2019",
keywords = "fluoropyrimidine, metformin, oxaliplatin, adjuvant therapy, adult, aged, Article, body mass, cancer risk, cancer staging, chemotherapy, colon cancer, controlled study, female, follow up, high risk patient, human, major clinical study, male, middle aged, mortality, non insulin dependent diabetes mellitus, overall survival, priority journal, randomized controlled trial, recurrence free survival, treatment duration, treatment outcome",
author = "C. Vernieri and F. Galli and L. Ferrari and P. Marchetti and S. Lonardi and E. Maiello and R.V. Iaffaioli and M.G. Zampino and A. Zaniboni and {De Placido}, S. and M. Banzi and A. Damiani and D. Ferrari and G. Rosati and R.F. Labianca and P. Bidoli and G.L. Frassineti and M. Nicolini and L. Pavesi and M.C. Tronconi and A. Buonadonna and S. Ferrario and G.L. Re and V. Adamo and E. Tamburini and M. Clerico and P. Giordani and F. Leonardi and S. Barni and A. Ciarlo and L. Cavanna and S. Gori and S. Cinieri and M. Faedi and M. Aglietta and M. Antista and K.F. Dotti and {Di Bartolomeo}, M. and Investigators, {on behalf of TOSCA (Three or Six Colon Adjuvant)}",
note = "Cited By :2 Export Date: 25 February 2020 CODEN: OCOLF Correspondence Address: Vernieri, C.; Fondazione IRCCS Istituto Nazionale dei TumoriItaly; email: claudio.vernieri@istitutotumori.mi.it Chemicals/CAS: fluoropyrimidine, 675-21-8; metformin, 1115-70-4, 657-24-9; oxaliplatin, 61825-94-3 Funding text 1: aFondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; bThe Italian Foundation for Cancer Research Institute of Molecular Oncology, Milan, Italy; cIRCCS Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; dAzienda Ospedaliero Universitaria Santa Maria della Misericordia, Udine, Italy; eSant{\textquoteright}Andrea Hospital, Sapienza University of Rome and IRCCS Istituto Dermopatico dell{\textquoteright}Immacolata, Rome, Italy; fIRCCS Istituto Oncologico Veneto, Padua, Italy; gOspedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; hIRCCS Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy; iIRCCS Istituto Europeo di Oncologia, Milan, Italy; jFondazione Poliambulanza, Brescia, Italy; kUniversit{\`a} Federico II, Naples, Italy; lIRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; mIRCCS San Martino-IST, Genoa, Italy; nAzienda Ospedaliera San Paolo, Milan, Italy; oOspedale San Carlo, Potenza, Italy; pASST Papa Giovanni XXIII, Bergamo, Italy; qOspedale San Gerardo dei Tintori, Monza, Italy; rIRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy; sAzienda USL Romagna, Cattolica, Rimini, Italy; tFondazione Salvatore Maugeri, Pavia, Italy; uHumanitas Clinical and Research Center, Rozzano, Milan, Italy; vCentro di Riferimento Oncologico, Aviano, Italy;wASST Fatebenefratelli-Ospedale Luigi Sacco, Milan, Italy; xAzienda Ospedaliera S. 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year = "2019",
month = mar,
day = "1",
doi = "10.1634/theoncologist.2018-0442",
language = "English",
volume = "24",
pages = "385--393",
journal = "Oncologist",
issn = "1083-7159",
publisher = "Wiley Blackwell",
number = "3",
}