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Prognosis of small cell lung cancer patients with diabetes treated with metformin

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Abstract

Backgrounds

It has been reported that metformin has an anticancer impact in various solid tumors, but its role in small cell lung cancer (SCLC) remains unclear. This study aimed to investigate the effect of metformin on survival in diabetic SCLC patients.

Methods

A total of 79 SCLC patients with diabetes treated in our hospital between 2000 and 2010 were enrolled. The clinicopathological data and survival time were collected and evaluated. Univariate and multivariate analyses were used to investigate the association between metformin use and the survival of SCLC.

Results

Among the 79 diabetic patients, 36 patients took metformin. The median OS and DFS were significantly better in the metformin group compared to non-metformin group (OS 18.0 vs 11.5 months, p < 0.001; DFS 10.8 vs 6.5 months, p < 0.001). Multivariate Cox analysis indicated that metformin use was an independent prognostic factor for long-term outcome (HR = 0.549, 95 % CI 0.198–0.978, p = 0.001).

Conclusions

The prognosis of SCLC patients with diabetes treated with metformin was improved, which might be considered a potential useful anticancer drug in treating SCLC patients.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006;24:4539–44.

    Article  PubMed  Google Scholar 

  3. Socinski MA, Weissman C, Hart LL, Beck JT, Choksi JK, Hanson JP, et al. Randomized phase II trial of pemetrexed combined with either cisplatin or carboplatin in untreated extensive-stage small-cell lung cancer. J Clin Oncol. 2006;24:4840–7.

    Article  CAS  PubMed  Google Scholar 

  4. Stupp R, Monnerat C, Turrisi AT 3rd, Perry MC, Leyvraz S. Small cell lung cancer: state of the art and future perspectives. Lung Cancer. 2004;45:105–17.

    Article  PubMed  Google Scholar 

  5. Schneider BJ. Management of recurrent small cell lung cancer. J Natl Compr Canc Netw. 2008;6:323–31.

    CAS  PubMed  Google Scholar 

  6. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.

    Article  PubMed  Google Scholar 

  7. Richardson LC, Pollack LA. Therapy insight: influence of type 2 diabetes on the development, treatment and outcomes of cancer. Nat Clin Pract Oncol. 2005;2:48–53.

    Article  PubMed  Google Scholar 

  8. Wu L, Rabe KG, Petersen GM. Do variants associated with susceptibility to pancreatic cancer and type 2 diabetes reciprocally affect risk? PLoS One. 2015;10:e0117230.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Gong Y, Wei B, Yu L, Pan W. Type 2 diabetes mellitus and risk of oral cancer and precancerous lesions: a meta-analysis of observational studies. Oral Oncol. 2015;51:332–40.

    Article  PubMed  Google Scholar 

  10. Yeo Y, Ma SH, Hwang Y, Horn-Ross PL, Hsing A, Lee KE, et al. Diabetes mellitus and risk of thyroid cancer: a meta-analysis. PLoS ONE. 2014;9:e98135.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Ma FJ, Liu ZB, Qu L, Hao S, Liu GY, Wu J, et al. Impact of type 2 diabetes mellitus on the prognosis of early stage triple-negative breast cancer in People’s Republic of China. Onco Targets Ther. 2014;7:2147–54.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Wolf I, Sadetzki S, Gluck I, Oberman B, Ben-David M, Papa MZ, et al. Association between diabetes mellitus and adverse characteristics of breast cancer at presentation. Eur J Cancer. 2006;42:1077–82.

    Article  PubMed  Google Scholar 

  13. Hjartaker A, Langseth H, Weiderpass E. Obesity and diabetes epidemics: cancer repercussions. Adv Exp Med Biol. 2008;630:72–93.

    Article  PubMed  Google Scholar 

  14. Bayraktar S, Hernadez-Aya LF, Lei X, Meric-Bernstam F, Litton JK, Hsu L, et al. Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer. Cancer. 2012;118:1202–11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Zheng L, Yang W, Wu F, Wang C, Yu L, Tang L, et al. Prognostic significance of AMPK activation and therapeutic effects of metformin in hepatocellular carcinoma. Clin Cancer Res. 2013;19:5372–80.

    Article  CAS  PubMed  Google Scholar 

  16. Tan BX, Yao WX, Ge J, Peng XC, Du XB, Zhang R, et al. Prognostic influence of metformin as first-line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes. Cancer. 2011;117:5103–11.

    Article  CAS  PubMed  Google Scholar 

  17. Lin JJ, Gallagher EJ, Sigel K, Mhango G, Galsky MD, Smith CB, et al. Survival of patients with stage IV lung cancer with diabetes treated with metformin. Am J Respir Crit Care Med. 2015;191:448–54.

    Article  CAS  PubMed  Google Scholar 

  18. He X, Esteva FJ, Ensor J, Hortobagyi GN, Lee MH, Yeung SC. Metformin and thiazolidinediones are associated with improved breast cancer-specific survival of diabetic women with HER2+ breast cancer. Ann Oncol. 2012;23:1771–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. He XX, Tu SM, Lee MH, Yeung SC. Thiazolidinediones and metformin associated with improved survival of diabetic prostate cancer patients. Ann Oncol. 2011;22:2640–5.

    Article  PubMed Central  PubMed  Google Scholar 

  20. van Meerbeeck JP, Fennell DA, De Ruysscher DK. Small-cell lung cancer. Lancet. 2011;378:1741–55.

    Article  PubMed  Google Scholar 

  21. Adelstein DJ, Tomashefski JF Jr, Snow NJ, Horrigan TP, Hines JD. Mixed small cell and non-small cell lung cancer. Chest. 1986;89:699–704.

    Article  CAS  PubMed  Google Scholar 

  22. Babakoohi S, Fu P, Yang M, Linden PA, Dowlati A. Combined SCLC clinical and pathologic characteristics. Clin Lung Cancer. 2013;14:113–9.

    Article  PubMed  Google Scholar 

  23. Mangum MD, Greco FA, Hainsworth JD, Hande KR, Johnson DH. Combined small-cell and non-small-cell lung cancer. J Clin Oncol. 1989;7:607–12.

    CAS  PubMed  Google Scholar 

  24. Nicholson SA, Beasley MB, Brambilla E, Hasleton PS, Colby TV, et al. Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens. Am J Surg Pathol. 2002;26:1184–97.

    Article  PubMed  Google Scholar 

  25. Rong B, Zhao C, Liu H, Ming Z, Cai X, Gao W, et al. Identification and verification of Hsp90-beta as a potential serum biomarker for lung cancer. Am J Cancer Res. 2014;4:874–85.

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Currie CJ, Poole CD, Jenkins-Jones S, Gale EA, Johnson JA, Morgan CL. Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care. 2012;35:299–304.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Mazzone PJ, Rai H, Beukemann M, Xu M, Jain A, Sasidhar M. The effect of metformin and thiazolidinedione use on lung cancer in diabetics. BMC Cancer. 2012;12:410.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Storozhuk Y, Hopmans SN, Sanli T, Barron C, Tsiani E, Cutz JC, et al. Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. Br J Cancer. 2013;108:2021–32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Eikawa S, Nishida M, Mizukami S, Yamazaki C, Nakayama E, Udono H. Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc Natl Acad Sci U S A. 2015;112:1809–14.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Rena G, Pearson ER, Sakamoto K. Molecular mechanism of action of metformin: old or new insights? Diabetologia. 2013;56:1898–906.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Memmott RM, Mercado JR, Maier CR, Kawabata S, Fox SD, Dennis PA. Metformin prevents tobacco carcinogen–induced lung tumorigenesis. Cancer Prev Res (Phila). 2010;3:1066–76.

    Article  CAS  Google Scholar 

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Acknowledgments

We thank Jeff Lee for critical reading of the manuscript.

Conflict of interest

All authors have no potential conflicts of interest.

Ethics Statement

The protocol of this study was approved by the Research Ethics Committee of Tianjin Hospital of ITCWM, Nankai Hospital, China.

Informed consent

Written informed consent was obtained from all patients who participated in this study.

Author information

Author notes

    Authors and Affiliations

    1. Department of Respiratory Medicine, Tianjin Hospital of ITCWM, Nankai Hospital, Sanwei Road, Nankai District, Tianjin, 300100, China

      T. Xu, L. Yang & F. Zhang

    2. Department of International Medical Center, Tianjin First Center Hospital, Fukang Road, Tianjin, 300192, China

      G. Liang

    Authors
    1. T. Xu
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    2. G. Liang
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    3. L. Yang
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    4. F. Zhang
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    Corresponding author

    Correspondence to T. Xu.

    Additional information

    T. Xu and G. Liang contributed equally to this work.

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    Xu, T., Liang, G., Yang, L. et al. Prognosis of small cell lung cancer patients with diabetes treated with metformin. Clin Transl Oncol 17, 819–824 (2015). https://doi.org/10.1007/s12094-015-1311-1

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    • DOI: https://doi.org/10.1007/s12094-015-1311-1

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