Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1 (5-Year IF – 2.0)
Journal Citation Indicator (JCI) (2023) – 0.4
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Index Copernicus  – 171.00; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 9, September, p. 1195–1199

doi: 10.17219/acem/69021

Publication type: original article

Language: English

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Effect of metformin in the prognosis of patients with smallcell lung cancer combined with diabetes mellitus

Hongyang Lu1,2,A,B,D, Fajun Xie2,B, Zhiyu Huang2,B, Jing Qin2,C,E, Na Han2,B, Weimin Mao1,A,F

1 Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, China

2 Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China

Abstract

Background. The prognosis for small-cell lung cancer (SCLC) is very poor, so a new therapeutic strategy and new drugs are imperative.
Objectives. The aim of this study was to examine the effect of metformin on the prognosis of patients with SCLC combined with diabetes mellitus (DM).
Material and Methods. From 2005 to 2013, 32 patients (4 female and 28 male) with SCLC combined with DM were included in this retrospective study at the Zhejiang Cancer Hospital, China. All patients were diagnosed with SCLC by pathological analysis and had received more than 4 cycles of chemotherapy. Metformin was used in 12 patients. Seventeen patients had limited-stage disease (LD) and 15 patients had extensive-stage disease (ED). Patients with LD SCLC were administered thoracic radiotherapy. The follow-up deadline was January 27, 2016. At that point, 4 patients were alive, 21 patients had died, and 7 patients did not participate in follow-up examinations.
Results. In patients with SCLC combined with DM using metformin, a complete response (CR) was observed in 4 patients, a partial response (PR) in 6 patients, a stable disease (SD) in 1 patient, and a progressive disease (PD) in 1 patient, whereas in patients who did not use metformin, CR was observed in 2 patients, PR in 15 patients, SD in 2 patients, and PD in 1 patient (p = 0.384). There was no difference in the median survival time (MST) between patients using metformin and those who did not (12 vs 13 months; p = 0.784). There was a trend toward prolonged MST in patients with LD SCLC using metformin compared with those who did not use metformin (58 vs 29 months; p = 0.084). There was no difference due to the use of metformin observed in MST of patients with ED SCLC (12 vs 13 months; p = 0.396).
Conclusion. Metformin use may have a prognostic benefit in patients with SCLC combined with DM. This combination is promising and further clinical trials are required.

Key words

small-cell lung cancer, diabetes mellitus, metformin, prognosis

References (20)

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.
  2. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016. doi: 10.3322/caac.21338
  3. Govindan R, Page N, Morgensztern D, 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;24:4539–4544.
  4. Leone A, Di Gennaro E, Bruzzese F, Avallone A, Budillon A. New perspective for an old antidiabetic drug: Metformin as anticancer agent. Cancer Treat Res. 2014;159:355–376.
  5. Guo Z, Cao M, You A, et al. Metformin inhibits the pro-metastatic effect of sorafenib in hepatocellular carcinoma by upregulating the expression of TIP30. Cancer Sci. 2016. doi: 10.1111/cas.12885
  6. Liang G, Ding M, Lu H, et al. Metformin upregulates E-cadherin and inhibits B16F10 cell motility, invasion and migration. Oncol Lett. 2015;10:1527–1532.
  7. Li L, Han R, Xiao H, et al. Metformin sensitizes EGFR-TKI-resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal. Clin Cancer Res. 2014;20:2714–2726.
  8. Morgillo F, Sasso FC, Della Corte CM, et al. Synergistic effects of metformin treatment in combination with gefitinib, a selective EGFR tyrosine kinase inhibitor, in LKB1 wild-type NSCLC cell lines. Clin Cancer Res. 2013;19:3508–3519.
  9. Ding L, Liang G, Yao Z, et al. Metformin prevents cancer metastasis by inhibiting M2-like polarization of tumor associated macrophages. Oncotarget. 2015;6:36441–36455.
  10. Teixeira SF, Guimarães Idos S, Madeira KP, Daltoé RD, Silva IV, Rangel LB. Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells. J Bras Pneumol. 2013;39:644–649.
  11. Inal A, Kaplan MA, Kucukoner M, et al. Is diabetes mellitus a prognostic factor for survival in patients with small cell lung cancer? Asian Pac J Cancer Prev. 2012;13:1491–1494.
  12. Tian RH, Zhang YG, Wu Z, Liu X, Yang JW, Ji HL. Effects of metformin on survival outcomes of lung cancer patients with type 2 diabetes mellitus: A meta-analysis. Clin Transl Oncol. Epub 2015 Oct 12.
  13. Takada M, Fukuoka M, Kawahara M, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: Results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002;20:3054–3060.
  14. Sun JM, Ahn YC, Choi EK, et al. Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer. Ann Oncol. 2013;24:2088–2092.
  15. Zatloukal P, Cardenal F, Szczesna A, et al. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol. 2010;21:1810–1816.
  16. Lara PN Jr, Natale R, Crowley J, et al. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: Clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009;27:2530–2535.
  17. Hermes A, Bergman B, Bremnes R, et al. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: A randomized phase III trial. J Clin Oncol. 2008;26:4261–4267.
  18. Lu HY, Wang XJ, Mao WM. Targeted therapies in small cell lung cancer (Review). Oncol Lett. 2013;5:3–11.
  19. Kong F, Gao F, Liu H, et al. Metformin use improves the survival of diabetic combined small-cell lung cancer patients. Tumour Biol. 2015;36: 8101–8106.
  20. Wheatley-Price P, Ma C, Ashcroft LF, et al. The strength of female sex as a prognostic factor in small-cell lung cancer: A pooled analysis of chemotherapy trials from the Manchester Lung Group and Medical Research Council Clinical Trials Unit. Ann Oncol. 2010;21:232–237.