Liposomal doxorubicin is less cardiotoxic than epirubicin in patients with breast cancer: evidence from a randomized clinical trial employing biological, tissue Doppler and standard echocardiographic endpoints.

Abstract

Abstract Abstract #6145 PURPOSE: Cardiomyopathy following anthracycline chemotherapy may have ominous clinical implications in cancer patients treated with this effective yet potentially toxic therapy. Liposomal anthracyclines (such as liposomal doxorubicin) have the potential for more selective uptake by cancer cells and reduced cardiac toxicity, but early detection at subclinical stage by means of non-invasive tests is pivotal to disclose treatment differences. We thus designed a randomized clinical trial, the Liposomal doxorubicin-Investigational chemotherapy-Tissue Doppler imaging Evaluation (LITE) pilot study to compare the safety of liposomal doxorubicin vs standard epirubicin in terms of clinical and subclinical cardiotoxicity.
 METHODS: Women with breast cancer and indication to anthracycline chemotherapy were randomized to liposomal doxorubicin or standard epirubicin. Multimodality non-invasive tests, including serial troponin, NT-pro-B-type natriuretic peptide (NT-pro-BNP), standard and tissue Doppler echocardiography were used at baseline and then during follow-up visits to identify subclinical cardiotoxicity.
 RESULTS: A total of 46 females were enrolled, with a follow-up of 11.0±1.4 months. Use of liposomal doxorubicin instead of epirubicin was associated, at follow-up, with significantly higher left ventricular systolic lateral wall velocities (9.89±2.00 cm/s vs 9.79±2.67 cm/s, P=0.011), and significantly smaller decreases in left ventricular ejection fraction (follow-up LVEF 60.8±4.8% vs 57.1±4.3%, P=0.038). In addition, we found significant correlations between peak NT-pro-BNP values and left ventricular ejection fraction (R=-0.451; P=0.021), and that early changes in diastolic and systolic tissue Doppler parameters could significantly predict much later changes in standard echocardiographic parameters, such as left ventricular ejection fraction (R=0.399; P=0.0035), end-diastolic diameter (R=-0.445; P=0.020), end-systolic diameter (R=-0.427; P=0.010), and deceleration time (R=-0.565; P=0.002).
 CONCLUSIONS: The present randomized clinical trial, by exploiting tissue Doppler imaging parameters, suggests that a chemotherapy regimen based on liposomal doxorubicin is less cardiotoxic than one based on standard epirubicin in the treatment of patients with breast cancer. Moreover, prolonged follow-up from the overall study cohort shows that NT-pro-BNP values and early changes in tissue Doppler parameters can significantly predict later alterations in standard echocardiographic parameters, thus providing a potential tool for early detection of subclinical cardiotoxicity. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6145.