Patients must have cytologic or histologic proof of adenocarcinoma of the pancreas.

All patients must be staged with a physical exam and CXR. Patients must have locally advanced disease defined as tumor extension to the celiac axis or SMA, or occlusion of the SMPV confluence (on contrast-enhanced CT).

There must be no radiographic evidence of metastatic disease.

Patients must have had no prior chemotherapy or irradiation.

Patients must have a baseline Karnofsky performance status of at least 60.

Patients must have adequate bone marrow reserve platelet count >100,000/mL, hemoglobin>9 g/dL, absolute granulocyte count must be >1,500 cells/mm3,serum creatinine must be <1.6 mg/dL. Serum bilirubin must be less than 5 mg/dL prior to therapy with endoscopic or percutaneous drainage if necessary.

Patients must have estimated life expectancy of at least 12 weeks.

Patients must be at least 18 years of age. There will be no upper age restriction.

Female patients must have had childbearing potential terminated by surgery, radiation, or menopause, or attenuated by use of an approved contraceptive method (intrauterine device [IUD], birth control pills, barrier device, or abstinence.

Patients cannot have hepatic or peritoneal metastases detected by ultrasound (US), CT scan, or laparotomy prior to chemoradiation.

Before receiving external beam irradiation, patients should be able to maintain adequate oral nutrition (90% to 100% of estimated need of calories and protein) and be free of significant nausea and vomiting.

Patients should have bilateral renal function, as determined on excretory urogram (IVP) or abdominal CT, or >2/3 of one functioning kidney must be able to be shielded from the radiation beam.

Patients must have no fever or evidence of infection or other coexisting medical condition that would preclude protocol therapy.

Patients must sign an informed consent form