Küçük Hücreli Dışı Akciğer Kanserli Hastalarda Metforminin Sağkalıma Etkisi

Yıl 2024, , 337 - 342, 19.09.2024

Ali Caner Özdöver , Evren Fidan , Şafak Dişli , Nejla Rakıcı , Seher Nazlı Kazaz

https://doi.org/10.33631/sabd.1216847

Öz

Amaç: Akciğer kanseri dünyada kansere bağlı ölümlerin en sık nedenidir ve bu hastalarda normal popülasyonda olduğu gibi Diabetes Mellitus (DM) görülebilir. Metformin diyabet tedavisinde en sık kullanılan biguainiddir. Meme, karaciğer ve prostat gibi farklı kanser türlerine sahip hastalarda yapılan çalışmalar, metformin kullanımının hayatta kalmaya katkıda bulunabileceğini göstermiştir. Bu çalışmanın amacı, küçük hücre dışı akciğer kanserli (KHDAK) hastalarda metforminin sağkalım üzerine etkisini değerlendirmektir.
Gereç ve Yöntemler: Çalışmamıza 85 eş zamanlı diyabet tanısı olan hasta dahil edilmiştir. DM tanısı için metformin kullanmayan hastalar kontrol grubu olarak alındı. Sağkalım analizi için son takip tarihi 31 Kasım 2020 olarak belirlendi. Hastaların nötrofil/lenfosit oranı (NLO) hesaplandı, alkalen fosfataz (ALP), laktat dehidrojenaz (LDH), karsinoembriyonik antijen (CEA) değerleri ve sağ kalıma katkıları incelendi.
Bulgular: Tüm hastalarda 1,3 ve 5 yıllık genel sağkalım oranları sırasıyla %76,0, %46,5 ve %34,3 ve medyan OS 64,1 (%95 GA: 44,7-83,5) olarak belirlendi. Lenf nodu pozitifliği, karaciğer metastazı ve ölüm oranları metformin alanlarda daha az sıklıkta görülmüştür. Genel sağkalım sonuçları ve sağkalım oranları metformin kullanmayan hastalarda daha kötüdür.
Sonuç: Metformin kullanımı ile beraber hiperinsülinemi ve hipergliseminin kontrol altına alınması sağkalıma katkı sağlayabilir. Glisemik kontrol ve insülin direnci amacıyla kullanılan metforminin KHDAK hastalarının sağ kalımına etkisinin belirlenmesi için daha geniş ve prospektif çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

metformin, diyabet, akciğer kanseri

The Effect of Metformin on Survival in Patients with Non-Small Cell Lung Cancer

Öz

Aim: Lung cancer is the most common cause of cancer- related deaths in the world. Diabetes mellitus (DM) can be seen frequently in the lung cancer patient group as well as in the normal population. Metformin is one of the most commonly used biguanide drugs in the treatment of DM. Studies conducted in patients with different types of cancer, such as breast, liver, and prostate, have shown that metformin use may contribute to survival. The aim of the study is to evaluate the effect of metformin on survival in patients with non-small cell lung cancer (NSCLC).
Matherial and Methods: In this study, 85 patients diagnosed with non-small cell lung cancer and concurrent type 2 DM retrospectively were analyzed, and the last follow-up date was 31.11.2020. Neutrophil/lymphocyte ratio (NLR) of the patients was calculated. Alkaline phosphatase (ALP), lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA) values and their contribution to survival were examined.
Results: The 1, 3, and 5-year overall survival rates for all patients were 76.0%, 46.5%, and 34.3%, respectively, and the median OS was 64.1 (95% CI: 44.7-83.5). Lymph node (LN) positivity, liver metastasis, and death rates were less common in the patient group receiving metformin. Overall survival (OS) results and determined survival rates were worse in the non-metformin patient group.
Conclusion: Metformin usage and the control of hyperinsulinemia and hyperglycemia may contribute to survival rates. Larger and prospective studies are needed to determine the effect of metformin which is used for glycemic control and insülin resistance, in NSCLC patients' survival.

Anahtar Kelimeler

lung cancer, metformin, diabetes mellitus

Kaynakça

• Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021; 71(1): 7-33.
• Xiao K, Liu F, Liu J, Xu J, Wu Q, Li X. The effect of metformin on lung cancer risk and survival in patients with type 2 diabetes mellitus: A meta-analysis. J Clin Pharm Ther. 2020; 45(4): 783-92.
• Lang-Lazdunski L. Surgery for nonsmall cell lung cancer. Eur Respir Rev. 2013; 22(129): 382-404.
• Vlastos F, Lacomme S, Wild P, Poulain S, Siat J, Grosdidier G, et al. Do evolving practices improve survival in operated lung cancer patients? A biobank may answer. J Thorac Oncol. 2009; 4(4): 505-11.
• Brancher S, Støer NC, Weiderpass E, Damhuis RAM, Johannesen TB, Botteri E, et al. Metformin use and lung cancer survival: a population-based study in Norway. Br J Cancer. 2021; 124(5): 1018-25.
• Yousef M, Tsiani E. Metformin in lung cancer: review of in vitro and in vivo animal studies. Cancers (Basel). 2017; 9(5): 45.
• Meng F, Song L, Wang W. Metformin ımproves overall survival of colorectal cancer patients with diabetes: a meta-analysis. J Diabetes Res. 2017; 2017: 5063239.
• Fatehi Hassanabad A, MacQueen KT. Molecular mechanisms underlining the role of metformin as a therapeutic agent in lung cancer. Cell Oncol (Dordr). 2021; 44(1): 1-18.
• Lin J, Gill A, Zahm SH, Carter CA, Shriver CD, Nations JA, et al. Metformin use and survival after non-small cell lung cancer: A cohort study in the US Military health system. Int J Cancer. 2017; 141(2): 254-63.
• Tian S, Lei HB, Liu YL, Chen Y, Dong WG. The association between metformin use and colorectal cancer survival among patients with diabetes mellitus: An updated meta-analysis. Chronic Dis Transl Med. 2017; 3(3): 169-75.
• Gupta G, de Jesus Andreoli Pinto T, Chellappan DK, Mishra A, Malipeddi H, Dua K. A clinical update on metformin and lung cancer in diabetic patients. Panminerva Med. 2018; 60(2): 70-5.
• Jin D, Guo J, Wu Y, Chen W, Du J, Yang L, et al. Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis. J Exp Clin Cancer Res. 2020; 39(1): 6.
• Pawałowska M, Markowska A. The influence of metformin in the etiology of selected cancers. Contemp Oncol (Pozn). 2012; 16(3): 223-9.
• Tang YL, Zhu LY, Li Y, Yu J, Wang J, Zeng XX, et al. Metformin Use Is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis. Biomed Res Int. 2017; 2017: 5905384.
• Yu X, Mao W, Zhai Y, Tong C, Liu M, Ma L, et al. Anti-tumor activity of metformin: from metabolic and epigenetic perspectives. Oncotarget. 2017; 8(3): 5619-28.
• Sośnicki S, Kapral M, Węglarz L. Molecular targets of metformin antitumor action. Pharmacol Rep. 2016; 68(5): 918-25.
• Chen YQ, Chen G. Combined therapeutic effect and molecular mechanisms of metformin and cisplatin in human lung cancer xenografts in nude mice. J Cancer Res Ther. 2015; 11(2): 324-30.
• Moro M, Caiola E, Ganzinelli M, Zulato E, Rulli E, Marabese, et al. Metformin enhances cisplatin-ınduced apoptosis and prevents resistance to cisplatin in co-mutated KRAS/LKB1 NSCLC. J Thorac Oncol. 2018; 13(11): 1692-704.
• Wen-Xiu X, Xiao-Wei Z, Hai-Ying D, Ying-Hui T, Si-Si K, Xiao-Fang Z, et al. Impact of metformin use on survival outcomes in non-small cell lung cancer treated with platinum. Medicine (Baltimore). 2018; 97(51): e13652.