RATIONALE: Drugs used in chemotherapy, such as epirubicin, oxaliplatin, fluorouracil, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy, surgery, and radiation therapy works in treating patients with locoregionally advanced cancer of the esophagus, gastroesophageal junction, or stomach.

OBJECTIVES:

Primary

• To assess the feasibility and tolerability of induction chemotherapy comprising epirubicin hydrochloride, oxaliplatin, and fluorouracil (EOF), followed by surgical resection and postoperative concurrent chemoradiotherapy comprising fluorouracil and cisplatin in patients with locoregionally advanced adenocarcinoma of the esophagus, gastroesophageal junction, or gastric cardia.

Secondary

• To determine the rate of complete and partial response to three courses of EOF induction chemotherapy.
• To compare the recurrence-free and overall survival of patients treated with this regimen vs historical controls at this institution.
• To compare patterns of failure in patients treated with this regimen vs historical controls at this institution.

OUTLINE:

• Induction chemotherapy: Patients receive epirubicin hydrochloride IV over 3-15 minutes and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV continuously on days 1-21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
• Surgery: Four weeks after completion of induction chemotherapy, patients with locoregionally confined disease (T0-4, N0-1, M0-1a) undergo transthoracic esophagogastrectomy or total gastrectomy with Roux-en-Y esophagojejunostomy, depending on the location and extent of the tumor at the time of surgery.
• Postoperative chemoradiotherapy: Beginning 6-10 weeks after surgery, patients undergo radiotherapy 5 days a week for approximately 6 weeks. Patients also receive fluorouracil IV continuously and cisplatin IV continuously over 96 hours in weeks 1 and 4 of radiotherapy.

After completion of study treatment, patients are followed every 8-12 weeks for 3 years.

Inclusion Criteria:

• Patients must have a histologic diagnosis of adenocarcinoma of the esophagus, gastroesophageal junction or gastric cardia, based on biopsy material or adequate cytologic exam.
• Patients must be clinically staged according to the AJCC 2002 staging system and must have either T3-4, or N1 or M1a disease. Staging should include at least an upper endoscopy with endoscopic ultrasound and an FDG-PET/CT scan.
• Patients must have an ECOG performance status of 0-1.
• Patients must have adequate bone marrow function as evidenced by: Absolute neutrophil count > 1,500/uL Platelet count > 100,000/uL
• Patients must have adequate renal function as evidenced by serum creatinine < 1.6 mg/dL
• Patients must have adequate hepatic function as evidenced by:Serum total bilirubin < 1.5 mg/dL Alkaline phosphatase < 3X the institutional ULN AST/ALT < 3X the institutional ULN
• Patients must have adequate pulmonary function as evidenced by an FEV1 > 50% predicted.
• Patients or their legal representatives must be able to read, understand, provide and sign informed consent to participate in the trial.
• Patients of childbearing potential agree to use an effective form of contraception during the study and for 90 days following the last dose of study medication (an effective form of contraception is an oral contraceptive or a double barrier method)
• Age > 18 years

Exclusion Criteria:

• Patients with any other diagnosis except for adenocarcinoma (squamous cell carcinoma, small cell carcinoma, mixed adenosquamous, lymphoma, sarcoma etc,) will be ineligible.
• Patients with any evidence of distant hematogenous or distant nodal disease (M1b) will be ineligible.
• No prior chemotherapy, radiation therapy or surgery for this malignancy will be allowed. Prior endoscopic debulking, laser therapy or dilatation will not exclude a patient.
• Patients with another active malignancy will not be eligible except for curatively treated basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized prostate cancer with a current PSA of < 1.0 mg/dL on 2 successive evaluations at least 3 months apart, with the most recent evaluation within 4 weeks of entry
• Patients with an active infection will not be eligible.
• Patients with known hypersensitivity to any of the components of oxaliplatin, epirubicin, fluorouracil or cisplatin will not be eligible.
• Patients who are receiving any other concurrent investigational therapy, or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy is defined as treatment for which there is currently no regulatory authority approved indication) will not be eligible.
• Patients with a baseline peripheral neuropathy greater than or equal Grade 2 will not be eligible.
• Patients who are pregnant or lactating will not be eligible.
• Patients with any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results, will not be eligible.
• Patients with any history of an allogeneic transplant will not be eligible.
• Patients with known infection with HIV, Hepatitis B or C (active, previously treated or both) will not be eligible.