The goal of this clinical research study is to learn if a combination of 5-FU, Folinic Acid and Oxaliplatin, given with radiation therapy, is effective in the treatment of gastric or gastroesophageal cancers that will be removed by surgery if possible. The safety of this combination therapy will also be studied.

Oxaliplatin and 5-FU are chemotherapy drugs that are commonly used to treat certain kind of cancers. Folinic Acid (leucovorin) acts with 5-FU to increase cancer cell death.

Before treatment begins, you will be asked questions about your medical history and have a complete physical exam. You will have around 1 tablespoon of blood drawn for routine tests. You will have your height and weight measured. You will have a chest x-ray and an electrocardiogram (ECG - a test that measures the electrical activity of the heart). You will also have a chest x-ray, barium study of the upper gastrointestinal tract, and a CT scan to check the size and location of the tumor. Women who are able to have children must have a negative blood pregnancy test.

All patients will have had a routine upper gastrointestinal tract endoscopy and biopsy with endoscopic ultrasound examination prior to participating in this trial. However, once participating in this trial, the upper gastrointestinal tract endoscopy will be repeated prior to surgery. This procedure involves examination of the esophagus, stomach, and duodenum by a flexible tube. Biopsies will be taken as necessary.

You will receive treatment with 5-FU as an infusion into a vein using a continuous 24- hour portable pump. This will start on Day 1 and will continue for 48 hours. You will need to carry this pump with you at all times for 48 hours. The pump is about the size of a Sony Walkman®. You will also receive Oxaliplatin as an infusion into a vein over 2 hours on Day 1. Folinic Acid will be given as an infusion into a vein over 30 minutes on Day 1. You will have 12 days to recover between chemotherapy treatments. These drugs may be given to you as an outpatient. Treatment will be repeated on Day 15. Two 14-day treatment periods are called one cycle. You will receive up to 8 weeks of the above chemotherapy (2 cycles).

If the cancer gets worse or you experience intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you.

Each week while you are receiving chemotherapy, around 1 tablespoon of blood will be drawn for routine tests.

Twelve days after you complete the second cycle of chemotherapy, you will begin to receive chemoradiotherapy (chemotherapy given at the same time as radiation therapy). Before chemoradiotherapy, you will be given a full physical, upper GI x-rays, about a tablespoon of blood will be drawn for routine blood tests, and if needed, a CT of the abdomen, chest and pelvis will be performed.

You will receive radiation therapy every weekday for a total of 25 sessions. During radiation therapy, 5-FU will be infused into your vein using a continuous infusion portable pump that you will carry with you day and night for up to 5 days (from Monday to Friday) of every week for 5 weeks. On Day 1 of radiation therapy each week, you will be given an infusion of Oxaliplatin into your vein over 2 hours for 5 weeks. During radiation therapy, you will be evaluated once a week and about one tablespoon of blood drawn for routine blood tests. Your doctor will discuss with you whether you will receive proton or x-ray radiation. If you receive proton radiation, it will be given in a building that is about a 5-minute drive from the M. D. Anderson radiation clinic.

If the cancer gets worse or you experience intolerable side effects, your treatment may be delayed or you may be taken off study and your doctor will discuss other treatment options with you.

Four to six weeks after the completion of chemoradiotherapy, the stage of the cancer will be evaluated. This includes drawing blood (about a tablespoon) for routine tests, chest x-ray, CT of the abdomen, chest, and pelvis (when necessary), upper GI endoscopy, and abdominal disease staging (if necessary).

When re-staging is complete, surgical removal of the primary tumor and lymph nodes will be attempted. All patients will be eligible for surgery. The J-tube will be left in your body for at least 8 weeks after the surgery to supplement your nutrition.

You will be asked to fill out side effect sheets throughout your participation in this research study. You will be asked questions regarding nausea, hair loss, fatigue, meals, and other questions regarding your daily activities.

Following this study, you will be asked to come for follow-up visits at M. D. Anderson at 3, 6, 9, and 12 months after surgery. You will then come in for visits every 6 months until Year 3, then once a year until Year 5. At these visits, you will have a full physical, about one tablespoon of blood drawn for routine tests, a chest x-ray, upper GI radiographs, upper GI endoscopy (every other visit) and CT of the abdomen (as needed).

This is an investigational study. Oxaliplatin is FDA approved and commercially available for the treatment of advanced colorectal cancer. Oxaliplatin is not approved in the US for the treatment of gastric cancer. 5-FU and folinic acid are commercially available drugs. The combination of these 3 drugs (Oxaliplatin + 5-FU + Folinic Acid) is investigational. A total of up to 58 patients will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Patients with potentially resectable adenocarcinoma of the stomach with histologic proof of adenocarcinoma, clinically staged T2-3, any N, M0 or T1N1M0 Gastric carcinoma may involve the gastroesophageal junction, however, the bulk of the tumor must be in the stomach (defined by radiographs, endoscopy, or endoscopic ultrasonography).
2. No prior major surgery of the stomach or radiation therapy to the stomach or immunotherapy or chemotherapy.
3. Patients must have a performance status of < 2 Zubrod scale.
4. Patients must have adequate bone marrow function (defined as peripheral absolute granulocyte count of >1,500/µL, and platelet count of > 100,000/µL), adequate liver function (bilirubin <= 1.5 mg/dl), and adequate renal function (creatinine <= 1.5 mg/dl).
5. Pretreatment evaluations must be done per the guidelines in Section 8.0.
6. A feeding jejunostomy must be inserted in all patients.
7. Patient must sign an informed consent prior to study entry.
8. Patient must be chronologic <= 75.

Exclusion Criteria:

1. Patients with T1N0 MO or T4 carcinoma documented by endoscopic ultrasonography.
2. Positive cytology of pleural, or pericardial effusion or patients with any peritoneal disease diagnosed by laparoscopy.
3. Biopsy proof of lymph node metastases outside the study field such as supraclavicular, mediastinal, or para-aortic nodes.
4. Evidence of metastatic disease to distant organs (biopsy is suggested for questionable findings).
5. Patients with cardiac disease graded as New York Heart Association Class III or IV, severe uncontrolled diabetes, hypertension, cerebrovascular disease, or infection.
6. Patients with diabetic neuropathy.
7. Abnormalities of mental status such that either the patient cannot fully comprehend the therapeutic implications of the protocol or comply with the requirements.
8. Presence of concurrent or previous malignancies in the past 5 years (except for resected squamous or basal cell carcinoma of the skin).
9. Pregnant women are excluded from study entry due to the potential teratogenic effects of the study treatment.

Adverse event collection during 16 week+ treatment period using Common Toxicity Criteria (CTC) to score chemotherapy events and acute radiation (< 90 days) toxicities.

Regular investigator assessment, regular laboratory testing, and routine questioning of participants during treatment and visits used for determination of adverse events.