Vitamin E Supplements in Treating Patients Undergoing Surgery for Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Vitamin E may help prevent the development of cancer. Studying samples of tissue from patients with colorectal cancer who receive Vitamin E before undergoing surgery in the laboratory may help doctors learn more about how Vitamin E changes biomarkers related to colorectal cancer. PURPOSE: This randomized early phase I trial is studying giving vitamin E supplements to see how it affects biomarkers in patients undergoing surgery for colorectal cancer.

Detailed Description
-----------------
OBJECTIVES: Determine the effect of high γ-tocopherol vitamin E mixture supplementation on plasma levels of α-, γ-, and δ-tocopherols, and prostaglandin E_2 in patients planning to undergo surgery for colorectal cancer by comparing the blood samples collected before and after the supplementation in each of the groups and analyzing levels of tocopherols and their metabolites in urine samples. Test the hypothesis that the supplementation reduces oxidative and nitrosative stress by measuring plasma levels of F_2-isoprostane, C-reactive protein, and 3-nitrotyrosine as well as urinary levels of 8-hydroxy-2-deoxyguanosine (8-OHdG). Determine the levels of α-, γ-, and δ-tocopherols in colon tissues and analyze immunohistochemically for cell proliferation, apoptosis, β-catenin localization, RXR expression, cyclooxygenase-2, 8-OHdG, and 3-nitrotyrosine levels in colon cancer tissue slides. OUTLINE: This is a multicenter study. The first 5 patients receive no supplements (to establish laboratory standards), all other patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive no intervention before undergoing planned surgery. Arm II: Patients receive oral high γ-tocopherol vitamin E mixture supplementation once daily for 1 week before undergoing planned surgery. Arm III: Patients receive oral high γ-tocopherol vitamin E mixture supplementation once daily for 2 weeks before undergoing planned surgery. Blood and urine samples are collected at baseline and on the day of surgery for tocopherol and biomarker analysis. A sample of colon tissue is removed during standard surgical resection for chemical analysis. Plasma, tumor tissue, and nontumorous tissues are analyzed for levels of F_2-isoprostane, 8-OHdG, 3-nitrotyrosine, and prostaglandin E_2 via enzyme immunoassays and for levels of α-, γ-, and δ-tocopherols via HPLC.

Official Title
-----------------
A Randomized Study to Investigate the Presence of Tocopherol Metabolites in the Colon

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Dietary Supplement: vitamin E
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Suspected or confirmed colorectal cancer meeting the following criteria: Scheduled for surgery as the initial treatment Referred to the Cancer Institute of New Jersey or the Robert Wood Johnson University Hospital No requirement for urgent surgery (i.e., surgery that cannot wait for 2 weeks) PATIENT CHARACTERISTICS: Not pregnant or nursing Negative pregnancy test Patients deemed in adequate health to undergo colon resection by their surgeon No uncontrolled diabetes, uncontrolled BP, chronic congestive heart failure, or history of renal insufficiency No personal or family history of bleeding disorders No known history of problems absorbing fats (e.g., Crohn disease, cystic fibrosis) PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior chemotherapy or radiotherapy for the treatment of this cancer More than 2 weeks since prior NSAIDs or corticosteroids No concurrent colestipol or orlistat No concurrent warfarin or dicumarol No concurrent supplementation of vitamin E A multivitamin containing ≤ 60 IU vitamin E allowed

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Arm I<br>Patients receive no intervention before undergoing planned surgery. | |
| Experimental: Arm II<br>Patients receive oral high γ-tocopherol vitamin E mixture supplementation once daily for 1 week before undergoing planned surgery. | Dietary Supplement: vitamin E<br>* Given orally<br>Other: laboratory biomarker analysis<br>* All patients undergo biomarker analyses<br>|
| Experimental: Arm III<br>Patients receive oral high γ-tocopherol vitamin E mixture supplementation once daily for 2 weeks before undergoing planned surgery. | Dietary Supplement: vitamin E<br>* Given orally<br>Other: laboratory biomarker analysis<br>* All patients undergo biomarker analyses<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma and urine levels of α-, γ-, and δ-tocopherols, and prostaglandin E2 |  | 4 years | 
| Plasma levels of F2-isoprostane, C-reactive protein, and 3-nitrotyrosine and urinary levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) |  | 4 years | 
| Presence in colon tissue of α-, γ-, and δ-tocopherols, cell proliferation and apoptosis indicators, β-catenin localization, RXR expression, and cyclooxygenase-2, 8-OHdG, and 3-nitrotyrosine levels |  | 4 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
colon cancer, rectal cancer