Genetic Trial to Study Diarrhea in Patients With Stage III Colon Cancer Who Are Receiving Chemotherapy

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Genetic testing may help predict how patients will respond to chemotherapy drugs and may help doctors plan more effective treatment with fewer side effects. PURPOSE: Genetic study to determine how genes affect the severity of diarrhea in patients with stage III colon cancer who are receiving chemotherapy.

Detailed Description
-----------------
OBJECTIVES: Determine whether the presence of a 7 allele at the UGT1A1 locus is associated with either grade 3-4 diarrhea or grade 4 neutropenia in patients with stage III colon cancer after treatment with irinotecan, fluorouracil, and leucovorin calcium. Determine whether polymorphisms in the TS enhancer and/or MTHFR gene are associated with grade 3-4 diarrhea in these patients after treatment with fluorouracil and leucovorin calcium. Determine whether polymorphisms in UGT1A1, TS, MTHFR, CYP3A4, or CYP3A5 are associated with either grade 3-4 diarrhea or grade 4 neutropenia in these patients after treatment with irinotecan, fluorouracil, and leucovorin calcium. OUTLINE: Patients are stratified according to prior therapy (irinotecan, fluorouracil, and leucovorin calcium vs fluorouracil and leucovorin calcium) and prior toxic effects (grade 3-4 diarrhea vs grade 4 neutropenia vs grade 1 or lower diarrhea AND grade 2 or lower neutropenia). Patients undergo collection of blood specimens for polymerase chain reaction and restriction fragment length polymorphism analysis. Genotyping assays are performed to determine UGT1A1 promoter genotyping, UGT1A1 coding polymorphisms, TS promoter polymorphisms, and MTHFR polymorphisms.

Official Title
-----------------
A Pharmacogenetic Case-Control Study of Severe Diarrhea and Life-Threatening Neutropenia in Patients Treated With Irinotecan, 5-Fluorouracil and Leucovorin

Conditions
-----------------
Colorectal Cancer, Diarrhea, Neutropenia

Intervention / Treatment
-----------------
* Genetic: mutation analysis
* Genetic: polymorphic microsatellite marker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed stage III adenocarcinoma of the colon Enrolled on CALGB-89803 and must fall into 1 of the following categories: Received irinotecan, fluorouracil, and leucovorin calcium and experienced at least 1 of the following: Grade 3-4 diarrhea Grade 4 neutropenia Grade 1 or lower diarrhea AND grade 2 or lower neutropenia Received fluorouracil and leucovorin calcium and experienced at least 1 of the following: Grade 3-4 diarrhea Grade 1 or lower diarrhea AND grade 2 or lower neutropenia PATIENT CHARACTERISTICS: Age 18 and over

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

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

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

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1<br>Patients undergo collection of blood specimens for polymerase chain reaction and restriction fragment length polymorphism analysis. Genotyping assays are performed to determine UGT1A1 promoter genotyping, UGT1A1 coding polymorphisms, TS promoter polymorphisms, and MTHFR polymorphisms. | Genetic: mutation analysis<br> <br> Genetic: polymorphic microsatellite marker analysis<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response |  | Up to 4 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenocarcinoma of the colon, stage III colon cancer, diarrhea, neutropenia