Effect of Anthracyclines and Cyclophosphamide on Cardiovascular Responses

Study Overview
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Brief Summary
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The present study aims to investigate the chronic effect of treatment with doxorubicin and cyclophosphamide on neurovascular control and blood pressure in women undergoing adjuvant treatment for breast cancer.

Detailed Description
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The development of new drugs and different adjuvant therapeutic regimens, based on the combination of anthracycline (A) and cyclophosphamide (C), have contributed greatly to improve survival rate in breast cancer patients. Despite the clinical benefits of this therapy, AC treatment can cause cardiovascular acute and chronic changes. In a recent investigation, we observed that an acute AC chemotherapy session increases sympathetic nervous activity and blood pressure in patients with breast cancer. The present study aims to investigate the chronic effects of AC regimen on sympathetic nervous activity, peripheral vasoconstriction, endothelial microparticles and blood pressure, in women with breast cancer.

Official Title
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Chronic Effect of Doxorubicin and Cyclophosphamide on Neurovascular Control and Blood Pressure in Women in Adjuvant Treatment for Breast Neoplasia

Conditions
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Cardiotoxicity, Cardiovascular Disease, Neurovascular Disorder, Endothelial Disfunction, Breast Cancer

Intervention / Treatment
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* Procedure: Physical Characteristics
* Procedure: Muscular Sympathetic Nervous Activity
* Diagnostic Test: Cardiac Function
* Diagnostic Test: Heart rate
* Diagnostic Test: Blood pressure
* Diagnostic Test: Blood Assessments
* Diagnostic Test: Muscle blood flow
* Diagnostic Test: Endothelium-dependent vascular function
* Diagnostic Test: Vascular intima-media thickness
* Diagnostic Test: Physical Capacity
* Drug: Anthracycline & Cyclophosphamide treatment scheme


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of stage II-III breast cancer starting adjuvant chemotherapy Exclusion Criteria: metastatic disease, hypercholesterolemia, diabetes, hypertension, severe lymphedema, organic disorders (renal failure, heart failure and chronic liver disease), obesity (BMI> 30) and, who are under pharmacological treatment with statins, angiotensin-converting enzyme inhibitors, losartan potassium, beta blockers or antioxidants

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pre and post chemotherapy assessments<br>The patients will be assessed before and after chemotherapy treatment. | Procedure: Physical Characteristics<br>* Body weight, height and waist circumference<br>Procedure: Muscular Sympathetic Nervous Activity<br>* Microneurography technique.<br>Diagnostic Test: Cardiac Function<br>* Echocardiography.<br>Diagnostic Test: Heart rate<br>* Electrocardiography<br>Diagnostic Test: Blood pressure<br>* Non-invasive photoplethysmography.<br>Diagnostic Test: Blood Assessments<br>* Serum and Plasma will be extracted by centrifugation. Endothelial microparticles by flow cytometry Interleukin-6 and tumor necrosis factor α by ELISA, High-sensitive reactive serum C-reactive protein by immunoturbidimetric assay, NT- ProBNP According to Central Laboratory, Hospital das Clinicas, HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo. Endothelin-1 by immunoenzymatic method Nitric oxide by gas chemiluminescence Lipoperoxidation by fluorimetry Carbonyl by spectrophotometer, and Superoxide Dismutase (SOD) by colorimetry.<br>Diagnostic Test: Muscle blood flow<br>* Venous occlusion plethysmography<br>Diagnostic Test: Endothelium-dependent vascular function<br>* Brachial ultrasound<br>Diagnostic Test: Vascular intima-media thickness<br>* Carotid ultrasound<br>Diagnostic Test: Physical Capacity<br>* Cardiopulmonary exercise test<br>Drug: Anthracycline & Cyclophosphamide treatment scheme<br>* Four session of intravenous (in bolus) infusion of doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 with an interval of 21 days between sessions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle sympathetic nerve activity | Change in muscular sympathetic nerve activity measured by microneurography | 15-20 days after the end of AC regimen | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle blood flow | Change in muscle blood flow measured by venous oclusion plethysmography | 15-20 days after the end of AC regimen | 
| Blood Pressure | Change in blood pressure measured by finometer | 15-20 days after the and of AC regimen | 
| Physical capacity | Change in physical capacity measured by cardiopulmonary exercise test | 15-20 days after the end of AC regimen | 
| Cardiac Function Impairment | Change in cardiac function measured by echocardiography | 15-20 days after the end of AC regimen | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chemotherapy, Endothelial Disfunction, Muscle Sympathetic Nerve Activity, Blood Pressure