Chemotherapy and Radiation Therapy After Surgery in Treating Patients With Stomach or Esophageal Cancer

OBJECTIVES: * Compare overall survival in patients with resected gastric adenocarcinoma treated with epirubicin, cisplatin, and infusional fluorouracil (5-FU) vs 5-FU bolus and leucovorin calcium before and after 5-FU plus radiotherapy. * Compare disease-free survival and local and distant recurrence rates in these patients treated with these regimens. * Correlate the expression of putative prognostic markers (including TS, ERCC-1, MSI, E-cadherin, EGFR, p27, COX-2, and c-erbB-2) with overall survival of patients treated with these regimens. * Correlate specific germline polymorphisms related to chemotherapy metabolism and resistance (including UGT2B7 \[epirubicin\], GST \[cisplatin\], ERCCI \[cisplatin\], XRCC1 \[cisplatin\], TS \[5-FU\], DPD \[5-FU\], and EGFR polymorphisms) with treatment-related toxicity and overall survival of these patients. * Correlate serum levels of insulin-like growth factor-1 (IGF-1), IGF-2, and IGF-binding protein 3 with overall survival of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to depth of tumor penetration (T1 or T2 vs T3 vs T4), lymph node involvement (0 vs 1-3), and extent of lymphadenectomy (D1 or D2 vs D0 or unknown). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive leucovorin calcium IV and fluorouracil (5-FU) IV on days 1-5 of courses 1, 3, and 4. Courses repeat every 28 days. During course 2, patients undergo radiotherapy 5 days a week and receive 5-FU IV continuously for 5 weeks. Patients rest for 28-35 days between course 2 and 3. * Arm II: Patients receive epirubicin IV over 3-15 minutes and cisplatin IV over 1 hour on day 1 and 5-FU IV continuously on days 1-21 during course 1. Beginning 1 week later, patients undergo radiotherapy 5 days a week and receive 5-FU IV continuously for 5 weeks. Patients rest for 28-35 days before beginning course 2 of chemotherapy. Patients then receive epirubicin, cisplatin, and 5-FU as in course 1. Treatment repeats every 21 days for 2 courses. Patients are followed every 3 months for 2 years, every 4 months for 2 years, and then annually for 3 years. PROJECTED ACCRUAL: A total of 824 patients will be accrued for this study.