RATIONALE: Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving fluorouracil together with oxaliplatin and leucovorin works in treating patients with metastatic stomach cancer or gastroesophageal junction cancer.

OBJECTIVES:

Primary

• Compare the response rate in patients with "good risk" genotype (TSER*2/*2 or TSER*2/*3 genotype [low TS expression]) to historical control response rates in non-genotype selected patients.

OUTLINE: This is a multicenter study.

Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on days 1 and 15. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.

Available tumor tissue samples are assessed for expression of TS at the mRNA and protein levels. The results are correlated with germline and tumor TSER genotypes as well as response to the study treatment regimen. Polymorphisms in other genes associated with treatment outcome or toxicity are also assessed.

After completion of study treatment, patients are followed periodically for 4 years.

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction

  • Metastatic disease

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan

• No known active brain metastases

  • Patients with treated brain metastases are eligible if stable off steroids for at least 30 days

PATIENT CHARACTERISTICS:

• ECOG performance status ≤ 2 (Karnofsky performance status ≥ 60%)
• Life expectancy ≥ 3 months
• WBC ≥ 3,000/μL
• Absolute neutrophil count ≥ 1,500/μL
• Platelets ≥ 100,000/μL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• AST or ALT ≤ 2.5 x ULN (< 5 x ULN if known liver metastases)
• Creatinine clearance ≤ 1.5 x ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 21 days after completion of study treatment
• No history of allergic reactions to fluorouracil or oxaliplatin
• No concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

• No prior therapy for metastatic disease

  • Prior neoadjuvant or adjuvant therapy is allowed if the disease-free interval has been longer than 6 months

• No other concurrent chemotherapy

• No concurrent combination anti-retroviral therapy for HIV-positive patients

• No concurrent routine prophylaxis with filgrastim (G-CSF)

• No other concurrent antineoplastic agents, including chemotherapy, radiation therapy, or biologic agents