RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving combination chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy works in treating patients who may undergo surgery for locally advanced pancreatic cancer.

OBJECTIVES:

• Determine the antitumor and clinical benefit response to neoadjuvant chemoradiotherapy comprising gemcitabine, fluorouracil, leucovorin calcium, and oxaliplatin in patients with potentially resectable locally advanced adenocarcinoma of the pancreas.
• Determine the toxic effects of this regimen in these patients.
• Determine the achieved steady-state plasma levels of gemcitabine and fluorouracil in these patients and correlate these plasma levels with clinical toxicity associated with this regimen.
• Determine the potential importance of polymorphic variations in genomic DNA of pertinent genes (whose protein products are targets of the antineoplastic drugs used in this study) on response to and toxicity of this regimen in these patients.
• Determine the gene expression profiles of primary and metastatic pancreatic tumors before and after treatment with this regimen.

OUTLINE:

• Neoadjuvant chemotherapy: Patients receive gemcitabine IV over 30 minutes and fluorouracil IV continuously over 24 hours on days 2 and 9, and leucovorin calcium orally on days 1 and 8 and IV on days 2 and 9. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
• Neoadjuvant chemoradiotherapy: Beginning on day 42, patients undergo chemoradiotherapy comprising oxaliplatin IV over 2 hours on days 42, 49, 56, 63, 70, and 77 and fluorouracil IV continuously on days 42-78 with external beam radiotherapy.
• Surgery: Patients undergo surgical resection 42-56 days after completion of chemoradiotherapy.
• Adjuvant chemotherapy: After post-operative recovery, patients receive 2 additional courses of gemcitabine, fluorouracil, and leucovorin calcium. If surgical resection is not possible, patients with stable or responsive disease resume gemcitabine, fluorouracil, and leucovorin calcium indefinitely in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Inclusion Criteria:

• Diagnosis of adenocarcinoma of the pancreas

  o Locally advanced disease

• Potentially resectable disease

• 19 years of age and over

• Karnofsky 60-100%

• Absolute granulocyte count ≥ 2,000/mm^3

• Platelet count ≥ 100,000/mm^3

• Bilirubin ≤ 2.0 mg/dL (in the absence of biliary obstruction)

  • If biliary obstruction is present, patients must undergo biliary decompression
  • Bilirubin ≤ 3.0 mg/dL after biliary drainage has been established

• Creatinine ≤ 1.6 mg/dL

Exclusion Criteria:

• No early stage resectable disease
• No concurrent non-steroidal anti-inflammatory medication
• No evidence of distant metastases to the liver or peritoneal area according to imaging studies and laparoscopic staging
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No serious uncontrolled cardiac arrhythmia
• Not pregnant or nursing
• No uncontrolled illness
• No active or ongoing infection requiring IV antibiotics
• No marked intolerance to 5-fluoropyrimidines (i.e., fluorouracil, floxuridine, capecitabine, or fluorocytosine)
• No allergy to sulfonamides, aspirin, or non-steroidal anti-inflammatory drugs
• No allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with study chemotherapy
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated noninvasive carcinoma
• No prior chemotherapy for pancreatic cancer
• No prior abdominal radiotherapy