LCZ 696 is superior to Valsartan in the prevention of cardiotoxity induced by trastuzumab, pertuzumab and Trastuzumab-DM1 monoclonal antibodies
N. Maurea, R. Paciello, G. Piscopo, G. Sorrentino, C. Maurea1, C. Coppola and C. De Lorenzo
Division of Cardiology, Istituto Nazionale Tumori – IRCCS – FONDAZIONE G. PASCALE, NAPLES, ITALY
Department of Molecular Medicine and Medical Biotechnology, University Federico II, Naples, Italy
Ceinge – Advanced
: J Clin Exp Oncol
Cardiotoxic effects related to anticancer drugs are among the leading causes of morbidity and mortality in cancer patients treated with Trastuzumab (T), Pertuzumab (P) and Trastuzumab-DM1 (TDM1) [1-3]. Sacubitril-valsartan (LCZ 696), a drug used for the treatment of heart failure in patients with a reduced ejection fraction, is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In this study, we aim to assess whether LCZ 696, administered during T, P or TDM1 treatment, reduces in vitro anticancer drugs-related cardiotoxicity, more efficiently respect to Valsartan (V). We used our in Vitro model, the H9C2 rat cardiomyoblasts, treated with 200 nM of T, P or TDM1 for 3 days, and then treated in the absence or presence of 10 μM of LCZ 696 or V for additional 3 days. Our results show that LCZ 696 is superior respect to V in the reduction of the cardiotoxic effects of T, P and TDM1, when administered to cultures of H9C2 cardiomyoblasts after antineoplastic treatments. Indeed, LCZ 696 was significantly more effective than V in reducing T related cardiotoxicity, increasing cell viability of 25 % more, respect to V (p<0.001). LCZ 696 is more strong in the reduction of P related toxicity, increasing cell viability of 35% more respect to V, with p<0.001. And finally, again more effective than V in reducing TDM1 toxicity, increasing cell viability of 10 % (p<0, 05).
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