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Giuseppe Biondi Zoccai, MD University of Modena and Reggio Emilia gbiondizoccai@gmail

Non-pegylated liposomial doxorubicin is less cardiotoxic than epirubicin in women with breast cancer: evidence from the LITE randomized study. Giuseppe Biondi Zoccai, MD University of Modena and Reggio Emilia gbiondizoccai@gmail.com

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Giuseppe Biondi Zoccai, MD University of Modena and Reggio Emilia gbiondizoccai@gmail

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  1. Non-pegylated liposomial doxorubicin is less cardiotoxic than epirubicin in women with breast cancer: evidence from the LITE randomized study Giuseppe Biondi Zoccai, MD University of Modena and Reggio Emilia gbiondizoccai@gmail.com for the LITE (Liposomial doxorubicin–Investigational chemotherapy–Tissue doppler imaging Evaluation) Investigators: Marzia LOTRIONTE, MD, Giovanni PALAZZONI, MD, Antonio ABBATE, MD, Eugenia DE MARCO, MD, Rosaria NATALI, MD, Silvia DI PERSIO, RN, and Francesco LOPERFIDO, MD

  2. BACKGROUND • Cardiomyopathy following anthracycline chemotherapy may have ominous clinical implications in cancer patients. • With the improved success of cancer treatments, more cases of late chemotherapy-related cardiac morbidity and mortality are seen. • The efficacy and safety of chemotherapy regimens is however often assessed only on the basis of cancer-free survival and on immediate chemotherapy toxicity (which does not take into account late cardiac [or pulmonary] toxicity).

  3. BACKGROUND (2) • In terms of cardiac toxicity, subclinical toxicity may precede clinically evident toxicity by several years, and thus clinically-based approaches are highly insensitive to assess cardiac toxicity in the short- to mid-term. • Anthracyclines are available in different formulations, and are administered as part of complex chemotherapy regimens in which multiple drugs with potential cardiotoxicity are given. • Liposomial anthracyclines have the potential for more selective uptake by cancer cells and reduced cardiac toxicity.

  4. BACKGROUND (3) • We thus designed an independent randomized clinical trial to specifically address cardiac safety using a highly sensitive approach (serial echocardioDoppler studies) and comparing a non-pegylated liposomial doxorubicin (Myocet)-based regimen vs a standard epirubicin-based as neoadjuvant or adjuvant strategies in women with non-metastatic breast cancer. • ClinicalTrials.gov identifier: NCT00531973

  5. METHODS • Women with non-metastatic breast cancer and indication to anthracycline chemotherapy for neoadjuvant or adjuvant therapy were randomized to a non-pegylated liposomial doxorubicin-based chemotherapy regimen or a standard epirubicin-based chemotherapy regimen (and radiotherapy as per standard of care at our center). • Baseline, post-chemotherapy and follow-up Doppler echocardiogram included standard left ventricular systolic and diastolic parameters, as well as tissue Doppler imaging (TDI) systolic and diastolic parameters.

  6. METHODS (2) • The primary end-points of the study were the changes from baseline to mid-term follow-up of TDI systolic function parameters, given their superior sensitivity and spatial resolution. • Additional data on standard systolic and diastolic echocardiographic parameters were also appraised. • Comparisons between treatment groups were based on Student t test or ANOVA for repeated measures for continuous variables, and 2 or Fisher exact tests for categorical variables. Last observation carried forward (LOCF) method was used for echocardiographic data.

  7. RESULTS • A total of 52 women were included, 29 randomized to non-pegylated liposomial doxorubicin and 23 to epirubicin, who were followed for an average of 23 months since starting chemotherapy.

  8. BASELINE CHARACTERISTICS

  9. BASELINE CHARACTERISTICS

  10. CHEMOTHERAPY REGIMENS

  11. ECHOCARDIOGRAPHY RESULTS • Repeated-measure analysis showed that a non-pegylated liposomial doxorubicin (Myocet)-based chemotherapy regimen was associated with more favorable changes in: • TDI septal Em/Am (p=0.012), • end-diastolic diameter (-4.4 mm, p=0.005), • end-systolic diameter (-4.4 mm, p=0.003).

  12. LOCF TDI DATA

  13. LOCF ECHOCARDIOGRAPHIC DATA *at bivariate/interaction testing

  14. RESULTS • At multivariable analysis concomitantly adjusting for age, diabetes mellitus, and follow-up duration, chemotherapy including non- pegylated liposomial doxorubicin was associated with more beneficial changes in left ventricular end-diastolic diameter (p=0.013) and end-systolic diameter (p=0.017).

  15. PEAK FOLLOW-UP BIOMARKERS *at bivariate/interaction testing

  16. CORRELATION ANALYSIS FOR TDI

  17. MULTIVARIABLE ANALYSIS FOR ECHOCARDIOGRAPHIC RESULTS

  18. LIMITATIONS • The study compares 2 different chemotherapy regimens based on liposomial doxorubicin or epirubicin, but differences include also doses, and concomitant treatments • Data on oncologic outcomes are still under collection and not included in the present report. • The limited sample size strongly limits the statistical power for comparisons of cardiovascular or oncologic outcomes.

  19. CONCLUSIONS • When sensitive tests are used, subclinical differences in cardiac toxicity can be measured. These differences are small but likely to have a clinical impact over the long-term. • Some differences in TDI can be seen earlier than changes in global LV systolic function (measured as LVEF), however TDI changes do not occur before changes in LV volumes, and are not independent of changes in LV volumes.

  20. CONCLUSIONS (2) • In this pilot clinical trial comparing two different chemotherapy strategy in women with breast cancer, the regimen based on non-pegylated liposomial doxorubicin appeared to be less cardiotoxic than the epirubicin-based treatment.

  21. Thank you for your attentionFor any correspondence: gbiondizoccai@gmail.comFor these and further slides on these topics feel free to visit the metcardio.org website:http://www.metcardio.org/slides.html

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