Cardiotoxicity Prevention in Breast Cancer Patients Treated With Anthracyclines and/or Trastuzumab
- Conditions
- CardiotoxicityBreast Cancer
- Interventions
- Registration Number
- NCT02236806
- Lead Sponsor
- Azienda Ospedaliero-Universitaria Careggi
- Brief Summary
The aim of the study is to analyze the protective impact on the cardiac damage of beta blockers and ACE inhibitors for breast cancer patients treated with anthracyclines-based chemotherapy with or without trastuzumab.
- Detailed Description
Over the years, due to the use of new generation therapeutic regimens, as well as the use of advanced radiation techniques, the curability of breast cancer reached an overall 10-year survival rate of approximately 80%.
Anthracyclines have a key role in the treatment of breast cancer. Many published studies showed a benefit of disease-free survival in patients with positive lymph nodes treated with anthracyclines-based regimens. Many anthracyclines and taxanes-based regimens are currently used in clinical practice in the treatment of breast cancer. Numerous randomized trials have confirmed the benefit of the addition of taxanes to anthracyclines.
Trastuzumab is a recombinant humanized monoclonal antibody with specificity for the extracellular domain of human epidermal growth factor receptor 2 (HER2). The use of trastuzumab administered sequentially or concurrently with adjuvant chemotherapy compared to chemotherapy in patients with HER2 positive was evaluated in several randomized trials. Many data concerning the incidence of adverse cardiovascular events acute, subacute and late are now available. The cardiac toxicity of anthracyclines may be acute, subacute and chronic. The acute toxicity occurs during or shortly after the infusion of the drug with arrhythmias, which in some cases leads to heart failure, pericarditis-myocarditis and electrocardiographic abnormalities. The acute toxicity is usually reversible in a dose-dependent manner. The acute and subacute toxicity are rare (1-4%). Data are available concerning clinically relevant cardiac toxicity with a chronic progressive deterioration of ventricular function up to heart failure.
Beside the cumulative dose risk factor, other unfavourable features such as advanced age, female sex, and the combination of anthracyclines and trastuzumab should be evaluated. In most cases, the late toxicity occurs within the first year following completion of chemotherapy but nevertheless the clinical manifestations can occur even after 10-20 years. This fact suggests that in women treated in (neo)adjuvant setting is strongly necessary an echocardiographic monitoring even after a longer time.
The aim of the study is to analyze the protective impact on the cardiac damage of beta blockers and ACE inhibitors for breast cancer patients treated with anthracyclines-based chemotherapy with or without trastuzumab, using myocardial strain imaging monitoring.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Female
- Target Recruitment
- 262
- Female
- Age >18 years
- Non-metastatic histologically confirmed primary invasive breast cancer
- Scheduled to receive neoadjuvant and/or adjuvant anthracyclines with or without anti-HER2 therapy
- Provided informed consent
- Able to swallow capsules
- LVEF > 50%
- Pregnant or lactating women
- Treatment with ACE-inhibitors or beta blockers at diagnosis
- History of NCI Common Toxicity Criteria for Adverse Effects (CTCAE) (version 4.0) Grade >2 symptomatic congestive heart failure (CHF), previous myocardial infarction, significant symptoms (Grade>2) relating to LVEF dysfunction, valvular disease, cardiac arrhythmia (Grade>3)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 Ramipril bisoprolol plus ramipril Arm 2 Placebo Bisoprolol plus placebo Arm 3 Ramipril Ramipril plus placebo Arm 3 Placebo Ramipril plus placebo Arm 4 Placebo Placebo Arm 1 Bisoprolol bisoprolol plus ramipril Arm 2 Bisoprolol Bisoprolol plus placebo
- Primary Outcome Measures
Name Time Method Global longitudinal strain (GLS) at months 6,9,12,24 Change in GLS at time-frame
Left ventricular ejection fraction (LVEF) at months 6,9,12,24 Change in LVEF (3-dimensional and 2-dimensional) at time-frame
- Secondary Outcome Measures
Name Time Method Indexed left ventricular end diastolic volume (EDVI) at months 6,9,12,24 Change in EDVI at time-frame
Indexed left ventricular end systolic volume (ESVI) at months 6,9,12,24 Change in ESVI at time-frame
Trial Locations
- Locations (1)
Azienda Ospedaliero-Universitaria Careggi, Florence University
🇮🇹Florence, Italy