Appraising cardiotoxicity associated with liposomal doxorubicin by means of tissue Doppler echocardiography end-points: rationale and design of the LITE (Liposomal doxorubicin-Investigational chemotherapy-Tissue Doppler imaging Evaluation) randomized pilot study.
BACKGROUND
Cardiomyopathy following anthracycline chemotherapy may have ominous clinical implications in cancer patients treated with this effective yet potentially toxic therapy. Early detection at subclinical stage is pivotal to minimize the risk of overt cardiotoxicity. Liposomal anthracyclines have the potential for more selective uptake by cancer cells and reduced cardiac toxicity.


OBJECTIVE
We designed a single-center 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
Whereas diagnostic and prognostic instruments effective at early recognition of cardiomyopathy are lacking, promising data have been reported for tissue Doppler imaging (TDI) echocardiography. The study will enroll 80 patients with breast cancer and indication to anthracycline chemotherapy, randomizing them in a 1:1 ratio to liposomal doxorubicin or standard epirubicin. The primary end-point will be the comparison of changes from baseline to 12-month follow-up of left ventricular TDI systolic function parameters, and the co-primary end-point will be based instead on changes in TDI diastolic function parameters. Among secondary end-points, we will adjudicate changes in standard 2-dimensional echocardiography parameters, including ejection fraction, peak values of biochemical markers of cardiac damage and heart failure, ie cardiac troponin T and BNP, overall survival, functional class, freedom from cancer recurrence, and adverse effects of chemotherapy.


CONCLUSIONS
Results of the LITE pilot study should provide important clinical and mechanistic insights on the promising role of liposomal anthracyclines in patients with breast cancer and indication to anthracycline chemotherapy (ClinicalTrials.gov identifier NCT00531973).
Lotrionte
Marzia
M
Division of Heart Failure and Cardiac Rehabilitation, Cardiovascular Department, Catholic University of the Sacred Heart, Rome, Italy. marzial76@yahoo.it
Palazzoni
Giovanni
G
Natali
Rosaria
R
Comerci
Gianluca
G
Abbate
Antonio
A
Di Persio
Silvia
S
Biondi-Zoccai
Giuseppe G L
GG
D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000000981:diagnostic imaging; D004317:Doxorubicin / Q000009:adverse effects*; D015150:Echocardiography, Doppler; D005260:Female; D006801:Humans; D008081:Liposomes; D010865:Pilot Projects
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin