• Overall survival [ Designated as safety issue: No ]
  

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.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (adenocarcinoma of the esophagus must involve the gastroesophageal junction) meeting the following criteria:

  • Tumor extension beyond muscularis propria and/or nodal involvement without evidence of M1 disease
  • Stage II, IIIA, IIIB, or IV (T2, N2, M0)
  • Stage IB (T1, N1, M0; T2, N0, M0 allowed if extension beyond muscularis propia)

• Prior en bloc resection, with curative intent, of all known tumor

  • No microscopic evidence of tumor at the line of resection
  • No noncontiguous resection
• No known unresected or recurrent disease at the distal or proximal line of stomach resection
• No metastatic disease

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 2.0 mg/dL
• AST no greater than 3 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL
• No unilateral renal function

Cardiovascular

• No myocardial infarction within the past 6 months
• No uncontrolled high blood pressure
• No unstable angina
• No symptomatic congestive heart failure
• No serious uncontrolled cardiac arrhythmia
• No New York Heart Association class III or IV heart disease
• No cardiac disease resulting in marked limitation or inability of physical activity

Other

• Stable weight for at least one week before study
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or fully resected noninvasive carcinoma in situ
• No other uncontrolled serious medical condition or psychiatric illness that would preclude study entry
• No active infection
• No peripheral neuropathy grade 2 or greater

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior biologic therapy allowed

Chemotherapy

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Prior hormonal therapy allowed

• No concurrent hormonal therapy except the following:

  • Steroids for adrenal failure
  • Hormones for non-disease-related conditions (e.g., insulin for diabetes)
  • Intermittent dexamethasone as an antiemetic

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics
• At least 3 weeks since prior surgery
• No more than 12 weeks since prior surgery