Cardioprotective effect of telmisartan in cancer patients treated with telmisartan.

Abstract

9153 Background: We showed previously in 31 cancer patients (pts) that early cardiac abnormalities, i.e. strain rate (SR) reduction detected by tissue Doppler imaging (TDI), occurred at epirubicin (EPI) doses of 200 mg/m2 and persisted throughout subsequent EPI doses and even up to 18 months. Renin-angiotensin system activation plays an important role in the pathogenesis of anthracycline-induced cardiotoxicity. Methods: A phase II randomized placebo-controlled study was designed to investigate the possible role of telmisartan (an antagonist of angiotensine II type I receptor) in preventing both early preclinical and late myocardial damage induced by EPI. The correlation with changes of biochemical/inflammatory markers was also assessed. Planned sample size was 100 pts. Inclusion criteria: 18–70 y, histologically confirmed cancer, previously untreated and candidates for an EPI-based regimen; LVEF ≥55%; ECOG PS 0- 2, no history of cardiac disease and previous mediastinal irradiation. Eligible pts were randomized to receive telmisartan 40 mg (1 tablet)/day or placebo, starting 1 week before EPI up to 6 months after the end of EPI administration. TDI as well as inflammatory/oxidative stress markers were assessed at baseline and after 7 days at EPI doses of 100, 200, 300, 400 mg/m2. Results: At January 2010 we enrolled 45 pts (M/F: 11/34, mean±SD age 53±10 years): 25 in Telmisartan and 20 in placebo arm. Forty-two pts completed EPI treatment (22 telmisartan and 20 placebo). A significant reduction of SR peak was observed at 200 mg/m2 of EPI both in the placebo (p<0.001) and the telmisartan arm (p=0.03). Vice versa, at higher cumulative doses (300 and 400 mg/m2 EPI) a significant higher reduction was observed in the placebo arm vs the telmisartan arm (p<0.001for both). Moreover, the diastolic function as assessed by Em/Am was significantly reduced in the placebo arm both at 200 and 300 mg/m2 of EPI (p <0.05 for both) whilst it was not reduced significantly in the telmisartan arm. Proinflammatory cytokines and oxidative stress markers did not change in the telmisartan arm whilst reactive oxygen species and IL-6 increased significantly in the placebo arm at EPI dosages≥ 200 mg/m2. Conclusions: The study is in progress up to pts accrual completion. No significant financial relationships to disclose.