Metformin does not improve survival in patients with hepatocellular carcinoma

World Journal of Gastroenterology

Volumn 20, Issue 42, 2014, Pages 15750-15755

  Bhat, Mamatha ^a,b   Chaiteerakij, Roongruedee ^a,c   Harmsen, William S ^d   Schleck, Cathy D ^d   Yang, Ju Dong ^a   Giama, Nasra H ^a   Therneau, Terry M ^d   Gores, Gregory J ^a   Roberts, Lewis R ^a  

^a MAYO CLINIC   (United States)

^b MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^c CHULALONGKORN UNIVERSITY   (Thailand)

^d Mayo Clinic   (United States)

Author keywords

Diabetes; Hepatocellular carcinoma; Lactic acidosis; Liver disease; Metformin; Survival

Indexed keywords

METFORMIN; ANTIDIABETIC AGENT;

ADULT; ALCOHOL LIVER DISEASE; ARTICLE; CANCER PATIENT; CANCER SURVIVAL; CHEMOPROPHYLAXIS; CHRONIC LIVER DISEASE; COHORT ANALYSIS; CONTROLLED STUDY; DIABETES MELLITUS; DIABETIC PATIENT; DRUG SAFETY; FATTY LIVER; FEMALE; FOLLOW UP; HEPATITIS B; HEPATITIS C; HUMAN; LIVER CELL CARCINOMA; LONGITUDINAL STUDY; MAJOR CLINICAL STUDY; MALE; OUTCOME ASSESSMENT; RETROSPECTIVE STUDY; AGED; CARCINOMA, HEPATOCELLULAR; DIABETES MELLITUS, TYPE 2; EPIDEMIOLOGY; KAPLAN MEIER METHOD; LIVER NEOPLASMS; MIDDLE AGED; MORTALITY; ODDS RATIO; PROGNOSIS; PROPORTIONAL HAZARDS MODEL; PROTECTION; RISK ASSESSMENT; RISK FACTOR; TIME; UNITED STATES; VERY ELDERLY; YOUNG ADULT;

ADULT; AGED; AGED, 80 AND OVER; CARCINOMA, HEPATOCELLULAR; DIABETES MELLITUS, TYPE 2; FEMALE; HUMANS; HYPOGLYCEMIC AGENTS; KAPLAN-MEIER ESTIMATE; LIVER NEOPLASMS; MALE; METFORMIN; MIDDLE AGED; MINNESOTA; ODDS RATIO; PROGNOSIS; PROPORTIONAL HAZARDS MODELS; PROTECTIVE FACTORS; RETROSPECTIVE STUDIES; RISK ASSESSMENT; RISK FACTORS; TIME FACTORS; YOUNG ADULT;

EID: 84912137896     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i42.15750     Document Type: Article

References (24)

1. Seeff LB, Hoofnagle JH. Epidemiology of hepatocellular carcinoma in areas of low hepatitis B and hepatitis C endemicity. Oncogene 2006; 25: 3771-3777 [PMID: 16799618 DOI: 10.1038/sj.onc.1209560]
2. El-Serag HB, Mason AC, Key C. Trends in survival of patients with hepatocellular carcinoma between 1977 and 1996 in the United States. Hepatology 2001; 33: 62-65 [PMID: 11124821]
3. El-Serag HB. Hepatocellular carcinoma: Recent trends in the United States. Gastroenterology 2004; 127: S27-S34 [PMID: 15508094 DOI: 10.1053/j.gastro.2004.09.013]
4. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008; 359: 378-390 [PMID: 18650514 DOI: 10.1056/NEJMoa0708857]
5. Zhu AX, Abrams TA, Miksad R, Blaszkowsky LS, Meyerhardt JA, Zheng H, Muzikansky A, Clark JW, Kwak EL, Schrag D, Jors KR, Fuchs CS, Iafrate AJ, Borger DR, Ryan DP. Phase 1/2 study of everolimus in advanced hepatocellular carcinoma. Cancer 2011; 117: 5094-5102 [PMID: 21538343 DOI: 10.1002/cncr.26165]
6. Villanueva A, Chiang DY, Newell P, Peix J, Thung S, Alsinet C, Tovar V, Roayaie S, Minguez B, Sole M, Battiston C, Van Laarhoven S, Fiel MI, Di Feo A, Hoshida Y, Yea S, Toffanin S, Ramos A, Martignetti JA, Mazzaferro V, Bruix J, Waxman S, Schwartz M, Meyerson M, Friedman SL, Llovet JM. Pivotal role of mTOR signaling in hepatocellular carcinoma. Gastroenterology 2008; 135: 1972-183, 1972-183, [PMID: 18929564 DOI: 10.1053/j.gastro.2008.08.008]
7. Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res 2006; 66: 10269-10273 [PMID: 17062558 DOI: 10.1158/0008-5472]
8. Memmott RM, Mercado JR, Maier CR, Kawabata S, Fox SD, Dennis PA. Metformin prevents tobacco carcinogen-induced lung tumorigenesis. Cancer Prev Res (Phila) 2010; 3: 1066-1076 [PMID: 20810672 DOI: 10.1158/1940-6207]
9. Tomic T, Botton T, Cerezo M, Robert G, Luciano F, Puissant A, Gounon P, Allegra M, Bertolotto C, Bereder JM, Tartare-Deckert S, Bahadoran P, Auberger P, Ballotti R, Rocchi S. Metformin inhibits melanoma development through autophagy and apoptosis mechanisms. Cell Death Dis 2011; 2: E199 [PMID: 21881601 DOI: 10.1038/cddis.2011.86]
10. Jonker JW, Schinkel AH. Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3). J Pharmacol Exp Ther 2004; 308: 2-9 [PMID: 14576340 DOI: 10.1124/jpet.103.053298]
11. Chen HP, Shieh JJ, Chang CC, Chen TT, Lin JT, Wu MS, Lin JH, Wu CY. Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: Population-based and in vitro studies. Gut 2013; 62: 606-615 [PMID: 22773548 DOI: 10.1136/gutjnl-2011-301708]
12. Donadon V, Balbi M, Mas MD, Casarin P, Zanette G. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease. Liver Int 2010; 30: 750-758 [PMID: 20331505 DOI: 10.1111/j.1478-3231.2010.02223]
13. Singh S, Singh PP, Singh AG, Murad MH, Sanchez W. Antidiabetic medications and the risk of hepatocellular cancer: A systematic review and meta-analysis. Am J Gastroenterol 2013; 108: 881-91; quiz 892 [PMID: 23381014 DOI: 10.1038/ajg.2013.5]
14. Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D. Diabetes and cancer: A consensus report. Diabetes Care 2010; 33: 1674-1685 [PMID: 20587728 DOI: 10.2337/dc10-0666]
15. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Diabetes increases the risk of hepatocellular carcinoma in the United States: A population based case control study. Gut 2005; 54: 533-539 [PMID: 15753540 DOI: 10.1136/gut.2004.052167]
16. Baig NA, Herrine SK, Rubin R. Liver disease and diabetes mellitus. Clin Lab Med 2001; 21: 193-207 [PMID: 11321935]
17. Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: An update. Nat Rev Cancer 2012; 12: 159-169 [PMID: 22337149]
18. Buzzai M, Jones RG, Amaravadi RK, Lum JJ, DeBerardinis RJ, Zhao F, Viollet B, Thompson CB. Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Res 2007; 67: 6745-6752 [PMID: 17638885 DOI: 10.1158/0008-5472.CAN-06-4447]
19. Bhalla K, Hwang BJ, Dewi RE, Twaddel W, Goloubeva OG, Wong KK, Saxena NK, Biswal S, Girnun GD. Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis. Cancer Prev Res (Phila) 2012; 5: 544-552 [PMID: 22467080 DOI: 10.1158/1940-6207.CAPR-11-0228]
20. Miyoshi H, Kato K, Iwama H, Maeda E, Sakamoto T, Fujita K, Toyota Y, Tani J, Nomura T, Mimura S, Kobayashi M, Morishita A, Kobara H, Mori H, Yoneyama H, Deguchi A, Himoto T, Kurokohchi K, Okano K, Suzuki Y, Murao K, Masaki T. Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo. Int J Oncol 2013 Dec 30; Epub ahead of print [PMID: 24378856 DOI: 10.3892/ijo.2013.2233]
21. Qu Z, Zhang Y, Liao M, Chen Y, Zhao J, Pan Y. In vitro and in vivo antitumoral action of metformin on hepatocellular carcinoma. Hepatol Res 2012; 42: 922-933 [PMID: 22524458]
22. Lega IC, Austin PC, Gruneir A, Goodwin PJ, Rochon PA, Lipscombe LL. Association between metformin therapy and mortality after breast cancer: A population-based study. Diabetes Care 2013; 36: 3018-3026 [PMID: 23633525 DOI: 10.2337/dc12-2535]
23. Aksoy S, Sendur MA, Altundag K. Demographic and clinico-pathological characteristics in patients with invasive breast cancer receiving metformin. Med Oncol 2013; 30: 590 [PMID: 23636908 DOI: 10.1007/s12032-013-0590-z]
24. Zhang X, Harmsen WS, Mettler TA, Kim WR, Roberts RO, Therneau TM, Roberts LR, Chaiteerakij R. Continuation of metformin use after a diagnosis of cirrhosis significantly improves survival of patients with diabetes. Hepatology 2014; Epub ahead of print [PMID: 24798175 DOI: 10.1002/hep.27199]