COMPARISON OF EPIRUBICIN AND DOXORUBICIN CARDIOTOXICITY INDUCED BY LOW-DOSES - EVOLUTION OF THE DIASTOLIC AND SYSTOLIC PARAMETERS STUDIED BY RADIONUCLIDE ANGIOGRAPHY

Background: Previous studies have demonstrated that epirubicin (EPI) h as a lower propensity to produce cardiotoxic effects than doxorubicin (DXR) at high doses. Hypothesis: The aim of the study was to compare t he cardiotoxicity induced by low doses of EPI and DXR in patients befo re and 1 month after the end of chemotherapy. Methods: In a prospectiv e study, 99 patients with a mean age of 51 +/- 12 years and without ca rdiac disease were studied before and 1 month after the end of chemoth erapy. Group 1 included 38 patients receiving 246 +/- 96 mg/m(2) of DX R and Group 2 included 61 patients receiving EPI with an equivalent do se of 219 +/- 92 mg/m(2) of DXR. Ejection fraction (EF) of the left ve ntricle (LV), peak ejection rate (PER), and peak filling rate (PFR) [e xpressed in end-diastolic volume/s (EDV/s)] were evaluated by gated ra dionuclide angiography; PFR/PER were also calculated. Results: Moderat e and similar alterations of left ventricular ejection fraction were s hown for low doses of anthracyclines. The EF of the LV decreased from 57 +/- 6% to 54 +/- 6% for DXR group (Group 1) (p = 0.005), and from 5 8 +/- 5% to 55 +/- 5% for the EPI group (Group 2) (p = 0.001). The PER of the left ventricle fell from 3.08 +/- 0.46 EDV/s to 2.74 +/- 0.49 in Group 1 (p = 0.001) and from 2.98 +/- 0.50 to 2.73 +/- 0.34 EDV/s i n Group 2 (p = 0.001). in contrast, no significant alteration of PFR a ppeared in Group 2 (from 2.72 +/- 0.51 to 2.62 +/- 0.41 EDV/s) for the equivalent dose of anthracycline, while PFR of the LV dropped from 2. 82 +/- 0.76 (EDV/s) to 2.41 +/- 0.55 after doxorubicin (p = 0.004). No difference was found between 1 and 12 months after the end of the tre atment in 25 patients in Group 1 and 28 patients in Group 2. These res ults confirm the advantage of EPI over DXR in terms of cardiotoxicity and help explain the relationship of cellular damage mechanisms with t he functional parameters of nuclear investigation. Conclusion: A possi ble explanation for specific alteration after DXR could be the increas ed production of semiquinone free radicals, which are known to induce membrane damage and, consequently, myocardial edema and diastolic alte ration.