Metformin Use and the Outcome of Metastatic Renal Cell Carcinoma Treated with Sunitinib or Pazopanib

. 2021 ; 13 () : 4077-4086. [epub] 20210521

Status PubMed-not-MEDLINE Jazyk angličtina Země Nový Zéland Médium electronic-ecollection

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid34054309

BACKGROUND: The anticancer properties of metformin have been suggested in numerous experimental studies and several retrospective clinical studies show that its use is associated with improved outcome of patients with cancer. However, limited data are available for patients with metastatic renal cell carcinoma (mRCC) treated with targeted therapy. The aim of this retrospective study was to assess the impact of the metformin use on survival of mRCC patients treated with sunitinib or pazopanib. METHODS: Clinical data from 343 patients with mRCC treated with sunitinib or pazopanib in the first line were analyzed. Progression-free survival (PFS) and overall survival (OS) were compared according to the use of metformin. RESULTS: The median PFS and OS for patients using metformin was 31.1 (95% CI 20.6-35.1) and 51.6 (95% CI 44.7-NR) months compared to 9.3 (95% CI 8.0-12.0) and 22.4 (95% CI 19.4-26.8) months for patients not using metformin (p<0.0001 and p=0.0002, respectively). Cox multivariate analysis shows that the use of metformin remains a significant factor for PFS (HR=0.55 [95% CI 0.343-0.883], p=0.013) and also for OS (HR=0.45 [95% CI 0.256-0.794], p=0.006). CONCLUSION: The present study results suggest that the use of metformin was associated with favorable outcome of mRCC patients treated with sunitinib or pazopanib.

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Znaor A, Lortet-Tieulent J, Laversanne M, et al. International variations and trends in renal cell carcinoma incidence and mortality. Eur Urol. 2015;67(3):519. doi:10.1016/j.eururo.2014.10.002 PubMed DOI

Srigley JR, Delahunt B, Eble JN, et al. The International Society of Urological Pathology (ISUP) Vancouver classification of renal neoplasia. Am J Surg Pathol. 2013;37(10):1469–1489. doi:10.1097/PAS.0b013e318299f2d1 PubMed DOI

Motzer RJ, Hutson TE, Tomczak P, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(22):3584–3590. doi:10.1200/JCO.2008.20.1293 PubMed DOI PMC

Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized Phase III trial. J Clin Oncol. 2010;28(6):1061–1068. doi:10.1200/JCO.2009.23.9764 PubMed DOI

Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2009;52(1):17–30. doi:10.1007/s00125-008-1157-y PubMed DOI

Cusi K, DeFronzo RA. Metformin: a review of its metabolic effects. Diabetes Rev. 1998;6(2):89–131.

Samuel SM, Varghese E, Kubatka P, et al. Metformin: the answer to cancer in a flower? Current knowledge and future prospects of metformin as an anti-cancer agent in breast cancer. Biomolecules. 2019;9(12):846. doi:10.3390/biom9120846 PubMed DOI PMC

Chen YC, Li H, Wang J. Mechanisms of metformin inhibiting cancer invasion and migration. Am J Transl Res. 2020;12(9):4885–4901. PubMed PMC

Chlebowski RT, McTiernan A, Aragaki AK, et al. Metformin and breast cancer incidence in postmenopausal diabetic women in the women’s health initiative (WHI). J Clin Oncol. 2011;29(11):3–1503. doi:10.1200/jco.2011.29.15_suppl.1503 DOI

Bansal M, Siegel E, Govindarajan R. The effect of metformin (M) on overall survival (OS) of patients (Pts) with colorectal cancer (CRC) treated with chemotherapy (CTX). J Clin Oncol. 2011;29(15):2608. doi:10.1200/jco.2011.29.15_suppl.2608 DOI

Mayer MJ, Klotz LH, Venkateswaran V. The effect of metformin use during docetaxel chemotherapy on prostate cancer-specific and overall survival of diabetic castration-resistant prostate cancer patients. J Urol. 2017;197(4):1068–1075. doi:10.1016/j.juro.2016.10.069 PubMed DOI

Lee CK, Jung M, Jung I, et al. Cumulative metformin use and its impact on survival in gastric cancer patients after gastrectomy. Ann Surg. 2016;263(1):96–102. doi:10.1097/SLA.0000000000001086 PubMed DOI

Lacroix O, Couttenier A, Vaes E, et al. Impact of metformin on gastric adenocarcinoma survival: a Belgian population based study. Cancer Epidemiol. 2018;53:149–155. doi:10.1016/j.canep.2018.02.001 PubMed DOI

Buchler T, Klapka R, Melichar B, et al. Sunitinib followed by sorafenib or vice versa for metastatic renal cell carcinoma – data from the Czech registry. Ann Oncol. 2012;23(2):395–401. doi:10.1093/annonc/mdr065 PubMed DOI

Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumours. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–216. doi:10.1093/jnci/92.3.205 PubMed DOI

Kahn BB, Alquier T, Carling D, et al. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005;1(1):15–25. doi:10.1016/j.cmet.2004.12.003 PubMed DOI

Sośnicki S, Kapral M, Węglarz L. Molecular targets of metformin antitumor action. Pharmacol Rep. 2016;68(5):918–925. doi:10.1016/j.pharep.2016.04.021 PubMed DOI

Woodard J, Joshi S, Viollet B, et al. AMPK as a therapeutic target in renal cell carcinoma. Cancer Biol Ther. 2010;10(11):1168–1177. doi:10.4161/cbt.10.11.13629 PubMed DOI PMC

Decensi A, Puntoni M, Goodwin P, et al. Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis. Cancer Prev Res (Phila). 2010;3(11):1451–1461. doi:10.1158/1940-6207.CAPR-10-0157 PubMed DOI

Gandini S, Puntoni M, Heckman-Stoddard BM, et al. Metformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders. Cancer Prev Res (Phila). 2014;7(9):867–885. doi:10.1158/1940-6207.CAPR-13-0424 PubMed DOI PMC

Li Y, Hu L, Xia Q, et al. The impact of metformin use on survival in kidney cancer patients with diabetes: a meta-analysis. Int Urol Nephrol. 2017;49(6):975–981. doi:10.1007/s11255-017-1548-4 PubMed DOI PMC

Jiralerspong S, Palla SL, Giordano SH, et al. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 2009;27(20):3297–3302. doi:10.1200/JCO.2009.19.6410 PubMed DOI PMC

Lin JJ, Gallagher EJ, Sigel K, et al. Survival of patients with stage IV lung cancer with diabetes treated with metformin. Am J Respir Crit Care Med. 2015;191(4):448–454. doi:10.1164/rccm.201407-1395OC PubMed DOI PMC

Choi Y, Kim TY, Oh DY, et al. The impact of diabetes mellitus and metformin treatment on survival of patients with advanced pancreatic cancer undergoing chemotherapy. Cancer Res Treat. 2016;48(1):171–179. doi:10.4143/crt.2014.292 PubMed DOI PMC

Psutka SP, Boorjian SA, Lohse CM, et al. The association between metformin use and oncologic outcomes among surgically treated diabetic patients with localized renal cell carcinoma. Urol Oncol. 2015;33(2):67 e15–23. doi:10.1016/j.urolonc.2014.07.008 PubMed DOI

Ersoy C, Kiyici S, Budak F, et al. The effect of metformin treatment on VEGF and PAI-1 levels in obese type 2 diabetic patients. Diabetes Res Clin Pract. 2008;81(1):56–60. doi:10.1016/j.diabres.2008.02.006 PubMed DOI

Lund SS, Tarnow L, Stehouwer CD, et al. Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes. Eur J Endocrinol. 2008;158(5):631–641. doi:10.1530/EJE-07-0815 PubMed DOI

Hirsch HA, Iliopoulos D, Struhl K. Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. Proc Natl Acad Sci USA. 2013;110(3):972–977. doi:10.1073/pnas.1221055110 PubMed DOI PMC

Esfahanian N, Shakiba Y, Nikbin B, et al. Effect of metformin on the proliferation, migration, and MMP-2 and −9 expression of human umbilical vein endothelial cells. Mol Med Rep. 2012;5(4):1068–1074. doi:10.3892/mmr.2012.753 PubMed DOI PMC

Hakimi AA, Chen L, Kim PH, et al. The impact of metformin use on recurrence and cancer-specific survival in clinically localized high-risk renal cell carcinoma. Can Urol Assoc J. 2013;7(11–12):E687–91. doi:10.5489/cuaj.1447 PubMed DOI PMC

Nayan M, Juurlink DN, Austin PC, et al. Canadian Drug Safety and Effectiveness Research Network (CDSERN). Medication use and kidney cancer survival: a population-based study. Int J Cancer. 2018;142(9):1776–1785. doi:10.1002/ijc.31204 PubMed DOI

Cheng JJ, Li H, Tan HS, et al. Metformin use in relation with survival outcomes of patients with renal cell carcinoma. Clin Genitourin Cancer. 2016;14(2):168–175. doi:10.1016/j.clgc.2015.12.012 PubMed DOI

Keizman D, Ish-Shalom M, Sella A, et al. Metformin use and outcome of sunitinib treatment in patients with diabetes and metastatic renal cell carcinoma. Clin Genitourin Cancer. 2016;14(5):420–425. doi:10.1016/j.clgc.2016.04.012 PubMed DOI

Hamieh L, McKay RR, Lin X, et al. Effect of metformin use on survival outcomes in patients with metastatic renal cell carcinoma. Clin Genitourin Cancer. 2017;15(2):221–229. doi:10.1016/j.clgc.2016.06.017 PubMed DOI

Pasha M, Sivaraman SK, Frantz R, et al. Metformin induces different responses in clear cell renal cell carcinoma caki cell lines. Biomolecules. 2019;9(3):113. doi:10.3390/biom9030113 PubMed DOI PMC

Chrom P, Stec R, Semeniuk-Wojtas A, et al. Fuhrman grade and neutrophil-to-lymphocyte ratio influence on survival in patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. Clin Genitourin Cancer. 2016;14(5):457–464. doi:10.1016/j.clgc.2016.02.005 PubMed DOI

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