Cardioprotective Empagliflozin for Cancer Patients Receiving Doxorubicin

Summary

Doxorubicin induced cardiomyopathy is the most common and serious side effect associated with doxorubicin treatment in cancer patients receiving doxorubicin. Studies have been shown that Empagliflozin can reduce cardiovascular mortality and hospitalization for heart failure in patients with heart failure with or without diabetes and current clinical trials indicate that SGLT2 inhibitors protect against heart failure outcomes and can reduce cardiac remodeling even in patients without diabetes. Empagliflozin had beneficial effects on the outcome of the cardiomyopathy and also has anti-tumor activity in animal studies, but clinical studies are still lacking. We are going to investigate the cardioprotective effect of Empagliflozin against doxorubicin induced cardiomyopathy. Objective: * Evaluate the prophylactic effect of using Empagliflozin "a selective inhibitor of the sodium glucose co-transporter 2 (SGLT2)" against doxorubicin induced cardiotoxicity in patients receiving doxorubicin-based chemotherapy. * Monitor the safety of adding empagliflozin to doxorubicin-based chemotherapy.

Timeline

Start

2023-11

Primary completion

2024-07

Completion

2024-08

Publications

• Results Kaya MG, Ozkan M, Gunebakmaz O, Akkaya H, Kaya EG, Akpek M, Kalay N, Dikilitas M, Yarlioglues M, Karaca H, Berk V, Ardic I, Ergin A, Lam YY. Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study. Int J Cardiol. 2013 Sep 1;167(5):2306-10. doi: 10.1016/j.ijcard.2012.06.023. Epub 2012 Jun 22.
• Results Janbabai G, Nabati M, Faghihinia M, Azizi S, Borhani S, Yazdani J. Effect of Enalapril on Preventing Anthracycline-Induced Cardiomyopathy. Cardiovasc Toxicol. 2017 Apr;17(2):130-139. doi: 10.1007/s12012-016-9365-z.
• Results Broeyer FJ, Osanto S, Suzuki J, de Jongh F, van Slooten H, Tanis BC, Bruning T, Bax JJ, Ritsema van Eck HJ, de Kam ML, Cohen AF, Mituzhima Y, Burggraaf J. Evaluation of lecithinized human recombinant super oxide dismutase as cardioprotectant in anthracycline-treated breast cancer patients. Br J Clin Pharmacol. 2014 Nov;78(5):950-60. doi: 10.1111/bcp.12429.
• Results Abuosa AM, Elshiekh AH, Qureshi K, Abrar MB, Kholeif MA, Kinsara AJ, Andejani A, Ahmed AH, Cleland JGF. Prophylactic use of carvedilol to prevent ventricular dysfunction in patients with cancer treated with doxorubicin. Indian Heart J. 2018 Dec;70 Suppl 3(Suppl 3):S96-S100. doi: 10.1016/j.ihj.2018.06.011. Epub 2018 Jun 18.
• Results Kalay N, Basar E, Ozdogru I, Er O, Cetinkaya Y, Dogan A, Inanc T, Oguzhan A, Eryol NK, Topsakal R, Ergin A. Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol. 2006 Dec 5;48(11):2258-62. doi: 10.1016/j.jacc.2006.07.052. Epub 2006 Nov 9.
• Results Eliaa SG, Al-Karmalawy AA, Saleh RM, Elshal MF. Empagliflozin and Doxorubicin Synergistically Inhibit the Survival of Triple-Negative Breast Cancer Cells via Interfering with the mTOR Pathway and Inhibition of Calmodulin: In Vitro and Molecular Docking Studies. ACS Pharmacol Transl Sci. 2020 Nov 11;3(6):1330-1338. doi: 10.1021/acsptsci.0c00144. eCollection 2020 Dec 11.
• Results Wang CY, Chen CC, Lin MH, Su HT, Ho MY, Yeh JK, Tsai ML, Hsieh IC, Wen MS. TLR9 Binding to Beclin 1 and Mitochondrial SIRT3 by a Sodium-Glucose Co-Transporter 2 Inhibitor Protects the Heart from Doxorubicin Toxicity. Biology (Basel). 2020 Oct 29;9(11):369. doi: 10.3390/biology9110369.
• Results Baris VO, Dincsoy AB, Gedikli E, Zirh S, Muftuoglu S, Erdem A. Empagliflozin Significantly Prevents the Doxorubicin-induced Acute Cardiotoxicity via Non-antioxidant Pathways. Cardiovasc Toxicol. 2021 Sep;21(9):747-758. doi: 10.1007/s12012-021-09665-y. Epub 2021 Jun 5.
• Results McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A. Corrigendum to: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2021 Dec 21;42(48):4901. doi: 10.1093/eurheartj/ehab670. No abstract available.
• Results Sabatino J, De Rosa S, Tamme L, Iaconetti C, Sorrentino S, Polimeni A, Mignogna C, Amorosi A, Spaccarotella C, Yasuda M, Indolfi C. Empagliflozin prevents doxorubicin-induced myocardial dysfunction. Cardiovasc Diabetol. 2020 May 15;19(1):66. doi: 10.1186/s12933-020-01040-5.
• Results Chang WT, Lin YW, Ho CH, Chen ZC, Liu PY, Shih JY. Dapagliflozin suppresses ER stress and protects doxorubicin-induced cardiotoxicity in breast cancer patients. Arch Toxicol. 2021 Feb;95(2):659-671. doi: 10.1007/s00204-020-02951-8. Epub 2020 Nov 19.
• Results Oh CM, Cho S, Jang JY, Kim H, Chun S, Choi M, Park S, Ko YG. Cardioprotective Potential of an SGLT2 Inhibitor Against Doxorubicin-Induced Heart Failure. Korean Circ J. 2019 Dec;49(12):1183-1195. doi: 10.4070/kcj.2019.0180. Epub 2019 Jul 31.
• Results Mustroph J, Wagemann O, Lucht CM, Trum M, Hammer KP, Sag CM, Lebek S, Tarnowski D, Reinders J, Perbellini F, Terracciano C, Schmid C, Schopka S, Hilker M, Zausig Y, Pabel S, Sossalla ST, Schweda F, Maier LS, Wagner S. Empagliflozin reduces Ca/calmodulin-dependent kinase II activity in isolated ventricular cardiomyocytes. ESC Heart Fail. 2018 Aug;5(4):642-648. doi: 10.1002/ehf2.12336.
• Results Connelly KA, Zhang Y, Visram A, Advani A, Batchu SN, Desjardins JF, Thai K, Gilbert RE. Empagliflozin Improves Diastolic Function in a Nondiabetic Rodent Model of Heart Failure With Preserved Ejection Fraction. JACC Basic Transl Sci. 2019 Feb 25;4(1):27-37. doi: 10.1016/j.jacbts.2018.11.010. eCollection 2019 Feb.
• Results Brzozowski JS, Skelding KA. The Multi-Functional Calcium/Calmodulin Stimulated Protein Kinase (CaMK) Family: Emerging Targets for Anti-Cancer Therapeutic Intervention. Pharmaceuticals (Basel). 2019 Jan 7;12(1):8. doi: 10.3390/ph12010008.
• Results Cardinale D, Colombo A, Bacchiani G, Tedeschi I, Meroni CA, Veglia F, Civelli M, Lamantia G, Colombo N, Curigliano G, Fiorentini C, Cipolla CM. Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation. 2015 Jun 2;131(22):1981-8. doi: 10.1161/CIRCULATIONAHA.114.013777. Epub 2015 May 6.

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