Neurovascular Changes Induced by Chemotherapy

Neurovascular Changes Provoked by Acute Administration Doxorubicin and Cyclophosphamide in Patients With Breast Cancer

The purpose of the present study was to test the hypothesis that doxorubicin and cyclophosphamide adjuvant chemotherapy (CHT) acutely induces neurovascular and hemodynamic changes in patients with breast cancer. To test this hypothesis, women with breast cancer (stage II-III) underwent two experimental sessions, saline (SL) and CHT. In the CHT session, doxorubicin (60 mg/m2) and cyclophosphamide (600mg/m2) were administred in 45 min. In the SL session, a matching saline volume to that of the CHT session was infused over 45 min.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Chemotherapeutic Toxicity
• Intervention / Treatment: Other: Chemotherapy

Detailed Description

The purpose of the present study was to test the hypothesis that doxorubicin and cyclophosphamide adjuvant chemotherapy (CHT) acutely induces neurovascular and hemodynamic changes in patients with breast cancer. To test this hypothesis, the patients were submitted in two experimental sessions, saline and chemotherapy, respectively. Saline Session. After fasting for 2 hours and abstaining from caffeine for 24 hours, the patients were positioned in a supine position. An intra-venous catheter was placed into the brachial venous in the contralateral arm of the breast surgery. Microelectrodes were positioned for MSNA measures in right leg, cuffs were placed around the leg for blood flow assessments and finger cuff was placed in 3 finger of hand for measurement of hemodynamic variables. After the instrumentation, an interval of 10 minutes was allowed, followed by blood sample collections for measurement of MPEs and, hemodynamic and neurovascular measures by period of 15 minutes (pre-infusion). Then, dexamethasone 20 mg and ondansetron 8 mg were administered i.v., followed by saline 0,09%, during 45 minutes. During saline infusion were continuously measured the neurovascular and hemodynamic variables. Finally, after saline administration, another blood sample was collected for MPEs dosing, followed by continuous measurement of hemodynamic and neurovacular variables by 15 minutes period (Figure 1).

Chemotherapy session. After a 2 to 3 day-interval, the patients were again positioned in a supine position in a temperature-controlled room (22oC). An intra-venous catheter was placed into the brachial venous in the contralateral arm of the breast surgery. Then, microelectrodes were positioned in the contralateral leg of the first session for MSNA measures. Likewise, cuffs were placed around the contralateral leg of the first protocol for blood flow assessments. After the instrumentation, an interval of 10 minutes was allowed, followed by blood sample collections and basal hemodynamic and neurovascular measures. Then, dexamethasone 20 mg and ondansetron 8 mg were administered, i.v., followed by doxorubicin and cyclophosphamide, during 45 minutes. During doxorubicin and cyclophosphamide infusions were continuously measured the neurovascular and hemodynamic variables. Finally, after doxorubicin plus cyclophosphamide administration, another blood sample was collected for EMPs dosing, followed by continuous measurement of hemodynamic and neurovacular variables by 15 minutes period

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Cerqueira Cesar
    • São Paulo, Cerqueira Cesar, Brazil
      • Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Breast cancer patients and prescription of adjuvant chemotherapy with antracycline and cyclophosphamide

Exclusion Criteria:

• Metastic disease
• Hypercholesterolemia
• Diabetes
• Hypertension
• Severe lymphedema
• Renal insufficient
• Heart failure
• Chronic liver disease
• Obesity, and treatment with some medications that inhibit cardiotoxicity, as beta-blocker angiotensin converting enzyme, statin, losartan and antioxidants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemotherapy; Infusion of doxorubicin and cyclophosphamide	Other: Chemotherapy; In chemoteraphy session, doxorubicin (60 mg/m2) and cyclophosphamide (600mg/m2) were administred in 45 min; Other Names: Doxorubicin and cyclophosphamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neural change induced by chemoterapy	Increase of muscle nerve sympathetic activivity	10 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vascular change induced by chemoterapy	Decrease of blood flow	10 min

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic change induced by chemoterapy	Increase of blood pressure	10 min

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Investigators: Principal Investigator: Carlos Negrão, University of Sao Paulo

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2016
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: October 25, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 13, 2017

Study Record Updates

• Last Update Posted (Actual): November 13, 2017
• Last Update Submitted That Met QC Criteria: November 7, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Chemotherapy; Blood flow; Muscle sympathetic nervous activity; Endothelial microparticles
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Doxorubicin
• Other Study ID Numbers: SDC 4227/15/054

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No