Effect of Anthracyclines and Cyclophosphamide on Cardiovascular Responses
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: pre and post chemotherapy assessments The patients will be assessed before and after chemotherapy treatment. |
Procedure: Physical Characteristics
Body weight, height and waist circumference
Procedure: Muscular Sympathetic Nervous Activity
Microneurography technique.
Diagnostic Test: Cardiac Function
Echocardiography.
Diagnostic Test: Heart rate
Electrocardiography
Diagnostic Test: Blood pressure
Non-invasive photoplethysmography.
Diagnostic Test: Blood Assessments
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.
Diagnostic Test: Muscle blood flow
Venous occlusion plethysmography
Diagnostic Test: Endothelium-dependent vascular function
Brachial ultrasound
Diagnostic Test: Vascular intima-media thickness
Carotid ultrasound
Diagnostic Test: Physical Capacity
Cardiopulmonary exercise test
Drug: Anthracycline & Cyclophosphamide treatment scheme
Four session of intravenous (in bolus) infusion of doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 with an interval of 21 days between sessions.
|
Outcome Measures
Primary Outcome Measures
- Muscle sympathetic nerve activity [15-20 days after the end of AC regimen]
Change in muscular sympathetic nerve activity measured by microneurography
Secondary Outcome Measures
- Muscle blood flow [15-20 days after the end of AC regimen]
Change in muscle blood flow measured by venous oclusion plethysmography
- Blood Pressure [15-20 days after the and of AC regimen]
Change in blood pressure measured by finometer
- Physical capacity [15-20 days after the end of AC regimen]
Change in physical capacity measured by cardiopulmonary exercise test
- Cardiac Function Impairment [15-20 days after the end of AC regimen]
Change in cardiac function measured by echocardiography
Eligibility Criteria
Criteria
Inclusion Criteria:
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diagnosis of stage II-III breast cancer
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starting adjuvant chemotherapy
Exclusion Criteria:
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metastatic disease,
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hypercholesterolemia, diabetes,
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hypertension,
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severe lymphedema,
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organic disorders (renal failure, heart failure and chronic liver disease),
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obesity (BMI> 30) and,
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who are under pharmacological treatment with statins, angiotensin-converting enzyme inhibitors, losartan potassium, beta blockers or antioxidants
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo | Sao Paulo | Brazil | 05403-900 |
Sponsors and Collaborators
- University of Sao Paulo General Hospital
- Universidade Federal Fluminense
- Hospital Israelita Albert Einstein
Investigators
- Principal Investigator: Carlos E Negrao, PhD, Instituto do Coracao, HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo
Study Documents (Full-Text)
None provided.More Information
Publications
- Abdel-Sayed S, Nussberger J, Aubert JF, Gohlke P, Brunner HR, Brakch N. Measurement of plasma endothelin-1 in experimental hypertension and in healthy subjects. Am J Hypertens. 2003 Jul;16(7):515-21.
- Barretto AC, Santos AC, Munhoz R, Rondon MU, Franco FG, Trombetta IC, Roveda F, de Matos LN, Braga AM, Middlekauff HR, Negrão CE. Increased muscle sympathetic nerve activity predicts mortality in heart failure patients. Int J Cardiol. 2009 Jul 10;135(3):302-7. doi: 10.1016/j.ijcard.2008.03.056. Epub 2008 Jun 26.
- Dolci A, Dominici R, Cardinale D, Sandri MT, Panteghini M. Biochemical markers for prediction of chemotherapy-induced cardiotoxicity: systematic review of the literature and recommendations for use. Am J Clin Pathol. 2008 Nov;130(5):688-95. doi: 10.1309/AJCPB66LRIIVMQDR. Review.
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- Laterza MC, de Matos LD, Trombetta IC, Braga AM, Roveda F, Alves MJ, Krieger EM, Negrão CE, Rondon MU. Exercise training restores baroreflex sensitivity in never-treated hypertensive patients. Hypertension. 2007 Jun;49(6):1298-306. Epub 2007 Apr 16.
- Negrão CE, Rondon MU, Tinucci T, Alves MJ, Roveda F, Braga AM, Reis SF, Nastari L, Barretto AC, Krieger EM, Middlekauff HR. Abnormal neurovascular control during exercise is linked to heart failure severity. Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1286-92.
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- Thijssen DHJ, Bruno RM, van Mil ACCM, Holder SM, Faita F, Greyling A, Zock PL, Taddei S, Deanfield JE, Luscher T, Green DJ, Ghiadoni L. Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. Eur Heart J. 2019 Aug 7;40(30):2534-2547. doi: 10.1093/eurheartj/ehz350.
- Breast Cancer Chemotherapy