• Pathologic complete response rate [ Designated as safety issue: No ]
• Frequency and severity of toxicity [ Designated as safety issue: Yes ]
• Correlation of DNA repair genes, target enzymes, and angiogenic factors with response, progression-free survival (PFS), and overall survival (OS) [ Designated as safety issue: No ]
• Correlation of haplotypes of candidate genes of TS, TP, ERCC-1, XPD, GST-P1, cyclooxygenase-2, EGF receptor, TGF-β, VEGF, and IL-8 with response, toxicity, PFS, and OS [ Designated as safety issue: Yes ]
• Feasibility of performing comparative genomic hybridization for analysis of DNA copy number changes in predicting response [ Designated as safety issue: No ]

• Pathologic complete response rate
• Frequency and severity of toxicity
• Correlation of DNA repair genes, target enzymes, and angiogenic factors with response, progression-free survival (PFS), and overall survival (OS)
• Correlation of haplotypes of candidate genes of TS, TP, ERCC-1, XPD, GST-P1, cyclooxygenase-2, EGF receptor, TGF-β, VEGF, and IL-8 with response, toxicity, PFS, and OS
• Feasibility of performing comparative genomic hybridization for analysis of DNA copy number changes in predicting response

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with radiation therapy works in treating patients with stomach cancer that can be removed by surgery.

OBJECTIVES:

• Determine the pathologic complete response rate in patients with primary gastric adenocarcinoma treated with neoadjuvant chemoradiotherapy comprising oxaliplatin, capecitabine, and radiotherapy.
• Assess the frequency and severity of toxicities associated with this regimen.
• Explore, preliminarily, the association between DNA repair genes (ERCC-1, XRCC1, GST-P1, XPD, XPA, ribonucleotide reductase), target enzymes (thymidylate synthase [TS], dihydropyrimide dehydrogenase, thymidine phosphorylase [TP]), and angiogenic factors (vascular endothelial growth factor [VEGF], epidermal growth factor [EGF], PD-ECGF, basic fibroblast growth factor, TSP-1 and -2, transforming growth factor [TGF]-β, and IL-8) and response to neoadjuvant therapy in patients with adenocarcinoma of the stomach.
• Explore, preliminarily, the association of haplotypes of candidate genes of TS, TP, ERCC-1, XPD, GST-P1, cyclooxygenase-2, EGF receptor, TGF-β, VEGF, and IL-8 with response and toxicity to neoadjuvant chemoradiation therapy in these patients.
• Explore, preliminarily, the feasibility of performing comparative genomic hybridization for analysis of DNA copy number changes in predicting response to neoadjuvant chemoradiation therapy.

OUTLINE: This is a multicenter, pilot study.

• Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on days 1 and 22 and oral capecitabine twice daily on days 1-14 and 22-35 in the absence of disease progression or unacceptable toxicity.
• Neoadjuvant chemoradiotherapy: Patients receive oral capecitabine twice daily on days 43-77 and undergo radiotherapy once daily on days 43-47, 50-54, 57-61, 64-68, and 71-75 in the absence of disease progression or unacceptable toxicity.
• Surgery: Patients with stable or responding disease undergo surgery 4-6 weeks after completion of chemoradiotherapy.

Tumor tissue is obtained at surgery or endoscopic biopsy. Gene expression analysis and comparative genomic hybridization testing are conducted on the tissue. Blood is drawn prior to beginning study treatment and is analyzed for germline polymorphisms.

After completion of study treatment, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

• Drug: capecitabine
• Drug: oxaliplatin
• Genetic: comparative genomic hybridization
• Genetic: microarray analysis
• Genetic: polymorphism analysis
• Other: laboratory biomarker analysis
• Procedure: conventional surgery
• Procedure: neoadjuvant therapy
• Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Histologically confirmed primary adenocarcinoma of the stomach, meeting the following criteria:

  • Newly diagnosed disease amenable to curative resection
  • Stage IB-III (T2-4)
• Measurable or nonmeasurable disease

• Enlarged lymph nodes outside of radiation fields must have preoperative biopsies

  • No positive lymph nodes outside of radiation fields
• No distant metastasis
• No gastroesophageal junction tumors

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• Absolute neutrophil count ≥ 1,500/mm³
• WBC ≥ 3,000/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 1.5 times upper limit of normal
• Albumin ≥ 3 g/dL
• Bilirubin normal
• No evidence of ischemic heart disease by EKG
• No coronary artery disease requiring active medical treatment
• No symptoms of angina
• No history of myocardial infarction
• No deep vein thrombosis within the past 12 months
• No pre-existing peripheral neuropathy
• No active pneumonia or inflammatory lung infiltrate
• No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for ≥ 5 years
• No clinically significant comorbid medical conditions that would prevent delivery of chemotherapy, radiotherapy, or the performance of surgery
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior and no concurrent sorivudine or brivudine
• No prior therapy for this malignancy, including chemotherapy, surgery, immunotherapy, or radiotherapy
• No prior coronary angioplasty or stenting
• No concurrent 2-dimensional or intensity-modulated radiotherapy