International Journal of Cancer Management

Published by: Kowsar

Combination of Metformin and Chemotherapy Decreases the Recurrence Rates of Epithelial Ovarian Cancers: A Randomized Clinical Trial

Bahareh Hamedi 1 , Azadeh Khalili 2 , Shohreh Roozmeh 1 , * , Golnaz Namazi 1 and Zahra Saraf 1
Authors Information
1 Oncology Division, Obstetrics and Gynecology Department, Shiraz University of Medical Sciences, Shiraz, Iran
2 Obstetrics and Gynecology Department, Jahrom University of Medical Sciences, Jahrom, Iran
Article information
  • International Journal of Cancer Management: July 2018, 11 (7); e11621
  • Published Online: July 10, 2018
  • Article Type: Research Article
  • Received: May 15, 2017
  • Revised: May 17, 2018
  • Accepted: May 21, 2018
  • DOI: 10.5812/ijcm.11621

To Cite: Hamedi B, Khalili A, Roozmeh S, Namazi G, Saraf Z. Combination of Metformin and Chemotherapy Decreases the Recurrence Rates of Epithelial Ovarian Cancers: A Randomized Clinical Trial, Int J Cancer Manag. 2018 ; 11(7):e11621. doi: 10.5812/ijcm.11621.

Copyright © 2018, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited
1. Background
2. Methods
3. Results
4. Discussion
  • 1. Cho KR, Shih I-M. Ovarian Cancer. Annu Rev Pathol. 2009;4(1):287-313. doi: 10.1146/annurev.pathol.4.110807.092246.
  • 2. Coleman RL, Ramirez PT, Gershenson DM. Neoplastic Diseases of the Ovary. Comprehensive Gynecology. Elsevier; 2013. p. 731-71. doi: 10.1016/b978-0-323-06986-1.00033-0.
  • 3. Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer: a review. Canc Biol Med. 2017;14(1):9-32. doi: 10.20892/j.issn.2095-3941.2016.0084.
  • 4. Arab M, Khayamzadeh M, Tehranian A, Tabatabaeefar M, Hosseini M, Anbiaee R, et al. Incidence rate of ovarian cancer in Iran in comparison with developed countries. Indian J Canc. 2010;47(3):322. doi: 10.4103/0019-509x.64721.
  • 5. Arab M, Noghabaei G. Ovarian cancer incidence in Iran and the world. Rep Radiother Oncol. 2013;1(2).
  • 6. Prat J. Staging classification for cancer of the ovary, fallopian tube, and peritoneum. Int J Gynecol Obstet. 2014;124(1):1-5. doi: 10.1016/j.ijgo.2013.10.001.
  • 7. Aletti GD, Gallenberg MM, Cliby WA, Jatoi A, Hartmann LC. Current Management Strategies for Ovarian Cancer. Mayo Clin Proc. 2007;82(6):751-70. doi: 10.4065/82.6.751.
  • 8. Bookman MA. The addition of new drugs to standard therapy in the first-line treatment of ovarian cancer. Ann Oncol. 2010;21(Supplement 7):vii211-7. doi: 10.1093/annonc/mdq368.
  • 9. Dizon DS, Weitzen S, Rojan A, Schwartz J, Miller J, DiSilvestro P, et al. Two for good measure: Six versus eight cycles of carboplatin and paclitaxel as adjuvant treatment for epithelial ovarian cancer. Gynecol Oncol. 2006;100(2):417-21. doi: 10.1016/j.ygyno.2005.10.031.
  • 10. Agarwal R, Kaye SB. Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat Rev Canc. 2003;3(7):502-16. doi: 10.1038/nrc1123.
  • 11. Belda-Iniesta C, Pernia O, Simo R. Metformin: a new option in cancer treatment. Clin Transl Oncol. 2011;13(6):363-7. doi: 10.1007/s12094-011-0669-y.
  • 12. Chan DK, Miskimins W. Metformin and phenethyl isothiocyanate combined treatment in vitro is cytotoxic to ovarian cancer cultures. J Ovarian Res. 2012;5(1):19. doi: 10.1186/1757-2215-5-19.
  • 13. Rattan R, Graham RP, Maguire JL, Giri S, Shridhar V. Metformin Suppresses Ovarian Cancer Growth and Metastasis with Enhancement of Cisplatin Cytotoxicity In Vivo. Neoplasia. 2011;13(5):483-IN28. doi: 10.1593/neo.11148.
  • 14. Evans JMM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. Bmj. 2005;330(7503):1304-5. doi: 10.1136/bmj.38415.708634.F7.
  • 15. Landman GWD, Kleefstra N, van Hateren KJJ, Groenier KH, Gans ROB, Bilo HJG. Metformin Associated With Lower Cancer Mortality in Type 2 Diabetes: ZODIAC-16. Diabetes Care. 2009;33(2):322-6. doi: 10.2337/dc09-1380.
  • 16. Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JMM. New Users of Metformin Are at Low Risk of Incident Cancer: A cohort study among people with type 2 diabetes. Diabetes Care. 2009;32(9):1620-5. doi: 10.2337/dc08-2175.
  • 17. Buzzai M, Jones RG, Amaravadi RK, Lum JJ, DeBerardinis RJ, Zhao F, et al. Systemic Treatment with the Antidiabetic Drug Metformin Selectively Impairs p53-Deficient Tumor Cell Growth. Canc Res. 2007;67(14):6745-52. doi: 10.1158/0008-5472.can-06-4447.
  • 18. Aljada A, Mousa SA. Metformin and neoplasia: Implications and indications. Pharmacol Therapeut. 2012;133(1):108-15. doi: 10.1016/j.pharmthera.2011.09.004.
  • 19. Kumar S, Meuter A, Thapa P, Langstraat C, Giri S, Chien J, et al. Metformin intake is associated with better survival in ovarian cancer. Cancer. 2013;119(3):555-62. doi: 10.1002/cncr.27706.
  • 20. Romero IL, McCormick A, McEwen KA, Park SY, Karrison T, Yamada SD, et al. Relationship of Type II Diabetes and Metformin Use to Ovarian Cancer Progression, Survival, and Chemosensitivity. Obstet Gynecol. 2012;119(1):61-7. doi: 10.1097/AOG.0b013e3182393ab3.
  • 21. Heintz APM, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, et al. Carcinoma of the Ovary. Int J Gynecol Obstet. 2006;95:S161-92. doi: 10.1016/s0020-7292(06)60033-7.
  • 22. Foley OW, Rauh-Hain JA, del Carmen MG. Recurrent epithelial ovarian cancer: an update on treatment. Oncology. 2013;27(4):288-94.
  • 23. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA: Canc J Clin. 2012;62(1):10-29. doi: 10.3322/caac.20138.
  • 24. Caton PW, Nayuni NK, Kieswich J, Khan NQ, Yaqoob MM, Corder R. Metformin suppresses hepatic gluconeogenesis through induction of SIRT1 and GCN5. J Endocrinol. 2010;205(1):97-106. doi: 10.1677/joe-09-0345.
  • 25. Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, et al. Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Exp Gerontol. 2005;40(8-9):685-93. doi: 10.1016/j.exger.2005.07.007.
  • 26. Memmott RM, Mercado JR, Maier CR, Kawabata S, Fox SD, Dennis PA. Metformin Prevents Tobacco Carcinogen-Induced Lung Tumorigenesis. Canc Prev Res. 2010;3(9):1066-76. doi: 10.1158/1940-6207.capr-10-0055.
  • 27. Feng Y-H, Velazquez-Torres G, Gully C, Chen J, Lee M-H, Yeung S-CJ. The impact of type 2 diabetes and antidiabetic drugs on cancer cell growth. J Cell Mol Med. 2011;15(4):825-36. doi: 10.1111/j.1582-4934.2010.01083.x.
  • 28. Hou M, Venier N, Sugar L, Musquera M, Pollak M, Kiss A, et al. Protective effect of metformin in CD1 mice placed on a high carbohydrate–high fat diet. Biochem Biophys Res Comm. 2010;397(3):537-42. doi: 10.1016/j.bbrc.2010.05.152.
  • 29. Phoenix KN, Vumbaca F, Fox MM, Evans R, Claffey KP. Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy. Breast Canc Res Treat. 2009;123(2):333-44. doi: 10.1007/s10549-009-0647-z.
  • 30. Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M. Metformin Is an AMP Kinase-Dependent Growth Inhibitor for Breast Cancer Cells. Canc Res. 2006;66(21):10269-73. doi: 10.1158/0008-5472.can-06-1500.
  • 31. Li D. Metformin as an antitumor agent in cancer prevention and treatment. J Diabetes. 2011;3(4):320-7. doi: 10.1111/j.1753-0407.2011.00119.x.
  • 32. Yang Y–X. Do Diabetes Drugs Modify the Risk of Pancreatic Cancer? Gastroenterology. 2009;137(2):412-5. doi: 10.1053/j.gastro.2009.06.022.
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