Plasma endothelin-1 as a marker for doxorubicin cardiotoxicity

The use of doxorubicin is often limited by cardiotoxicity that can lead to congestive heart failure (CHF). Although various techniques have been used to predict its cardiotoxicity, none has proven useful. We reported 2 patients in whom the level of plasma endothelin (ET)-1 rose progressively during doxorubicin treatment of breast cancer, and who subsequently developed CHF. Accordingly, we conducted a prospective study of 30 consecutive patients, 23 with breast cancer and 7 with small-cell lung cancer, who were treated with doxorubicin. Serial changes in plasma ET-1 during doxorubicin treatment were measured by a specific radioimmunoassay, and plasma levels of atrial natriuretic peptide (ANP) were determined by a sensitive immunoradiometric assay. M-mode echocardiography was performed serially to monitor the fractional shortening (FS) and the left ventricular ejection fraction (LVEF). The plasma concentrations of ET-1 rose progressively in 5 of the 30 patients during doxorubicin treatment. Two of the 5 patients developed clinically overt CHF after developing cumulative doses of doxorubicin of 500 and 480 mg/m2. Serial measurement of plasma levels of ANP, FS and LVEF showed no abnormalities until the development of CHF. Another 25 patients who had received doxorubicin (cumulative doses ranging from 400 to 660 mg/m2) and had not developed CHF showed no appreciable change in plasma ET-1 or other markers. This prospective study suggests that plasma ET-1 may be useful for predicting the risk of doxorubicin-induced cardiotoxicity.