• Antitumor and clinical benefit response [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  
• Correlation of achieved steady-state plasma levels with clinical toxicity [ Designated as safety issue: Yes ]
  
• Importance of polymorphic variations in genomic DNA of pertinent genes on response and toxicity [ Designated as safety issue: Yes ]
  
• Gene expression profiles of primary and metastatic pancreatic tumors before and after treatment [ Designated as safety issue: No ]
  

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.

DISEASE CHARACTERISTICS:

• Diagnosis of adenocarcinoma of the pancreas

  • Locally advanced disease
• Potentially resectable disease
• No evidence of distant metastases to the liver or peritoneal area according to imaging studies and laparoscopic staging

PATIENT CHARACTERISTICS:

Age

• 19 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count ≥ 2,000/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• 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

Renal

• Creatinine ≤ 1.6 mg/dL

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No serious uncontrolled cardiac arrhythmia

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for pancreatic cancer

Endocrine therapy

• Not specified

Radiotherapy

• No prior abdominal radiotherapy

Surgery

• Not specified