The purpose of this study is to find out what effects, good and bad, the chemotherapy drugs gemcitabine (Gemzar) and paclitaxel (Taxol) have in combination with twice daily radiation treatment on locally advanced pancreatic cancer.

Based on our previous experience with the use of a weekly paclitaxel dose of 60 mg/m2 and hyperfractionated radiation therapy 63.8 Gy, we are conducting this study incorporating the use of Gemcitabine at a dose level of 75 mg/m2/week in addition to our prior protocol.

Inclusion Criteria:

1. Pathologically confirmed adenocarcinoma of the pancreas.
2. Patients must have locally advanced/unresectable disease based on institutional standardized criteria of unresectability.
3. Patients with residual disease after resection (R-1 or -2, micro and macroscopic residual) are eligible.
4. Patients with biliary or gastroduodenal obstruction must have drainage prior to starting chemoradiation.
5. All malignant disease must be encompassed within a single irradiation field (12 x 12 cm maximum).
6. All patients must have radiographically assessable disease.
7. Electrocardiogram (EKG), chest x-ray, abdominal computed tomography (CT)/magnetic resonance imaging (MRI) scan must be obtained within four weeks of study entry.
8. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
9. Required entry laboratory parameters: granulocytes >/= 1,800/µl, platelet count >/= 100,000/µl, bilirubin < 2.0 mg/dL, alanine aminotransferase (ALT) < 3 x upper limit of normal, and creatinine < 3.0 mg/dL.
10. Signed study-specific consent form prior to study entry.

Exclusion Criteria:

1. Patients who have evidence of metastatic disease in the major viscera and/or peritoneal seeding or ascites.
2. Previous irradiation to the planned field; or previous chemotherapy for pancreatic cancer (Gemzar® or Taxol®).
3. Malignancy (within the past two years) except for non-melanomatous skin cancer or carcinoma in situ of the cervix, uterus, or bladder.
4. Patients who have significant infection or other coexistent medical condition that would preclude protocol therapy.