Abstract 3824: Cardioprotective Effect of Telmisartan in Cancer Patients Treated With Epirubicin
PURPOSE: It was previously shown that (i) free radicals and RAAS play an important role in the pathogenesis of cardiotoxicity induced by epirubicin (EPI); (ii) Telmisartan (Tel) inhibits activation of superoxide sources like NADPH oxidase, mitochondria, and xanthine oxidase.
METHODS: A phase II placebo-controlled study was designed to investigate the possible role of Tel, an AngII type-1 receptor antagonist, in preventing preclinical myocardial damage induced by EPI. We examined 36 patients (26 women, 10 men, mean±SD age 56±13 years) affected by a variety of solid cancers, previously untreated and candidates for an EPI-based regimen, and free from cardiac disease. Eligible patients were randomized to receive Tel (40 mg/day) or placebo, starting 1 week before chemotherapy. Patients were studied by means of conventional echocardiography, tissue Doppler (TDI) and Strain (S) and S rate (SR) imaging. We also measured plasma levels of reactive oxygen species (ROS) and of the antioxidative defense capacity, by detecting glutathione peroxidase activity (GPx). All parameters were assessed at baseline and 7 days after every new 100 mg/m2 EPI dose.
RESULTS: A significant impairment of SR peak was observed at the 200 mg/m2 EPI dose with no significant difference between Tel and placebo (1.41±0.31s−1 vs 1.59±0.36 s−1; p=ns). Moreover, a significant increase in ROS in comparison with respective basal values was found in the placebo arm (406±91 FORT-U vs 525±56 FORT-U; p<0.05), but not in the Tel arm (455±64 FORT-U vs 463±83 FORT-U; p=n.s.). GPx showed a significant reduction at the 200 mg/m2 EPI in both Tel and placebo-treated patients. At growing cumulative doses of EPI the SR impairment became less pronounced in the Tel arm showing a significant difference between the two arms at the 300 mg/m2 of EPI (1.69±0.42 s−1 vs 1.34±0.18 s−1; p<0.001) and at the 400 mg/m2 of EPI (1.74±0.27 s−1 vs 1.38±0.24 s−1; p<0.001).
CONCLUSIONS: We confirmed our previous data that EPI cardiotoxicity is primarily related to the inactivation of the cardiac antioxidant defences. Besides, we showed that Tel can reduce EPI-induced radical species and antagonize the early myocardial impairment. Present study will continue on a larger population of patients.