Cardiac morphologic and functional changes induced by epirubicin chemotherapy.

Abstract

Cardiac toxicity was evaluated in 24 patients who received epirubicin as a single chemotherapeutic agent, in doses of either 30 mg/m2 every week (11 patients) or 90 mg/m2 every 3 weeks (13 patients). The total doses of epirubicin ranged from 180 mg/m2 to 918 mg/m2 (mean, 491 +/- 187). No patient had prior heart disease, hypertension, mediastinal irradiation, or chemotherapy with other anthracycline agents. None of the patients developed overt heart failure, significant arrhythmias, ECG alterations, or roentgenographic changes in heart size. There was no significant change in the mean value of echocardiographic percent fractional shortening before and after epirubicin therapy. Patients receiving epirubicin doses less than 450 mg/m2 had minimal hemodynamic disturbances; however, no cut-off point separating two significantly different subpopulations could be demonstrated. Endomyocardial biopsy was performed on all patients; 20 biopsies were evaluable. Histologic and ultrastructural changes were similar to those caused by other anthracycline agents. A strong correlation was demonstrated between total dose of epirubicin and pathologic change as quantified using the Billingham scale (r = .7, P = .0006). A cut-off point beyond which there was a probability of increased pathologic damage was statistically defined at 450 mg/m2 of epirubicin. Severe pathologic alterations and moderate hemodynamic changes were observed in only one patient, who received 918 mg/m2 of epirubicin. Patients who are expected to receive epirubicin in excess of 450 mg/m2 should be monitored for cardiac toxicity, and continuation of epirubicin therapy beyond 900 mg/m2 should be based on the results of monitoring.

Drugs ten years later: Epirubicin

“…The clinical experience has confirmed that EPI causes cumulative dose dependent heart failure and cardiac morphological alterations to the myocardium which appear identical to those described for DOX, and mainly consist of dilatation of sarcoplasmic reticulum, myofibrillar loss and interstitial fibrosis [37,38]. However, a number of reports have now established that the cardiotoxic potency of EPI is significantly lower than that of the parent anthracycline [37][38][39].…”

Scintigraphic Techniques for Early Detection of Cancer Treatment–Induced Cardiotoxicity

“…Some patients with normal resting LVEF show an abnormal response to exercise. Furthermore, several reports have shown that the LVEF at rest correlates poorly with early myocardial damage as determined with endomyocardial biopsy (72)(73)(74). A certain critical mass of cell damage must occur before LVEF begins to decrease (75).…”

“…With electron microscopy, morphologic changes were observed, including distended sarcotubular systems, myofibrillar loss, and cytoplasmic vacuolization (73). Morphologic damage in the myocytes and subsequent diffuse myocyte lysis produce the progressive functional cardiac deterioration in these patients (75).…”

Cardiac Toxicity in Breast Cancer Survivors: Review of Potential Cardiac Problems

“…Biopsy specimens from doxorubicin-treated patients have loss of myofibrils, vacuolization of cytoplasm, dilation of sarcoplasmic reticulum, and necrosis (113,114). Electron microscopy of biopsies from patients with trastuzumab-induced cardiotoxicity does not show the classic Billingham changes of anthracycline exposure but have focal vacuoles, pleomorphic mitochondria, myocardial hypertrophy, and interstitial fibrosis (10,115).…”