Impact of Adjuvant Chemotherapy in Patients With Colon Cancer

Study Overview
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Brief Summary
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The present study aims to investigate the impact of adjuvant chemotherapy with 5-FU isolated and associated with oxaliplatin in cardiac autonomic control and endothelium-dependent vascular function in patients undergoing colectomy for stages II and III colon cancer. Will be performed evaluation of cardiac and vascular function, autonomic control, functional capacity and blood evaluations.

Detailed Description
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Cancer is a major public health problem. Colorectal cancer is the third most common cancer in men and women around the world. Despite advances in surgical and pharmacological treatment, this type of cancer remains a leading cause of cancer death in Western countries. The adjuvant chemotherapy treatment based on the use of fluoropyrimidine, especially 5-fluorouracil (5-FU) is the mainstay of the pharmacological treatment of colorectal cancer. This treatment showed benefit in overall survival and progression-free survival in the adjuvant treatment of patients with stage II and III disease. In the last decade, the combination treatment with oxaliplatin has shown benefit in patients with either metastatic disease as with locoregional disease who underwent surgical treatment. However, the increased use of 5-FU and oxaliplatin, and increased patient survival have caused increased incidence of adverse events. 5-FU has cardiotoxic effects that may range from 1.2 to 18% depending upon the drug administration. Another adverse event of chemotherapy for colon cancer is neurotoxicity. Peripheral neuropathy is one of the toxicities associated with treatment with Oxaliplatin and its characteristics to be dose-dependent and cumulative. Thus, the adjuvant chemotherapy with 5-FU and oxaliplatin may cause cardiotoxicity, changes in vascular function and increased oxidative stress. What is not known are the effects of treatment of 5-FU and oxaliplatin in cardiac autonomic modulation and peripheral vascular function. Therefore, the present study aims to investigate the impact of adjuvant chemotherapy with 5-FU isolated and associated with oxaliplatin in cardiac autonomic control and endothelium-dependent vascular function in patients undergoing colectomy for stages II and III colon cancer. Will be performed evaluation of cardiac and vascular function, autonomic control, functional capacity and blood evaluations.

Official Title
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Impact of Adjuvant Chemotherapy in Cardiovascular Autonomic Regulation in Patients With Colon Cancer

Conditions
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Colon Cancer, Adjuvant Chemotherapy

Intervention / Treatment
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* Drug: adjuvant chemotherapy with 5-FU isolated
* Drug: adjuvant chemotherapy with 5-FU associated with oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scale of Performance Status 0 - 1 Patients submitted to colectomy for adenocarcinoma of colon stages II and III. Exclusion Criteria: Severe pulmonary disease Decompensated cardiovascular disease Neurological disease Insulin-dependent diabetes mellitus Dialysis renal insufficiency

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients with stage II disease undergoing adjuvant 5-FU treatment will be allocat in chemotherapy-1 group, while stage III patients undergoing combined adjuvant chemotherapy (5FU + Oxaliplatin) will be allocat to the Chemotherapy group -2.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Quimioterapy 1<br>adjuvant chemotherapy with 5-FU isolated | Drug: adjuvant chemotherapy with 5-FU isolated<br>* Patients submitted to adjuvant chemotherapy with 5-FU isolated<br>|
| Active Comparator: Quimioterapy 2<br>adjuvant chemotherapy with 5-FU associated with oxaliplatin | Drug: adjuvant chemotherapy with 5-FU associated with oxaliplatin<br>* Patients submitted to adjuvant chemotherapy with 5-FU associated with oxaliplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiac function evaluation | Cardiac function will be assessed by two-dimensional (B-mode) echocardiography, pulsed Doppler | Change from Baseline cardiac function at 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| vascular function evaluation | Vascular function will be assessed by high resolution Doppler ultrasound | Change from Baseline vascular function at 6 months | 
| autonomic control evaluation | autonomic control will be assessed by microneurography and heart rate variability | Change from autonomic control at 6 months | 
| functional capacity evaluation | functional capacity will be assessed by cardiopulmonary exercise test | Change from Baseline functional capacity at 6 months | 
| Proinflammatory cytokines | Proinflammatory cytokines will be assessed by blood evaluations | Change from Baseline Proinflammatory cytokines at 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colon cancer, adjuvant chemotherapy, sympathetic nerve activity, peripheral vascular function