Inclusion Criteria:

1. Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinate process is required prior to treatment. Islet cell tumors are not eligible.
2. Patients must be staged with a physical exam, CXR, and contrast-enhanced CT. Only potentially resectable patients are eligible. Potentially resectable defined as: a) no extra pancreatic disease, b) no evidence (on CT) of tumor extension to the celiac axis or SMA, and c) no evidence (CT or angiogram) of occlusion of the SMV or SMPV confluence. Visceral angiography is optional. Laparoscopic staging is not part of the pretreatment evaluation for this study. Laparoscopy may be performed prior to planned laparotomy at surgeon's discretion. Staging needs to be done within 28 days of enrollment.
3. Patients cannot have known hepatic or peritoneal metastases detected by ultrasound (US), CT scan, or laparotomy prior to chemoradiation.
4. There will be no upper age restriction; patients with Karnofsky performance status greater than 70 are eligible.
5. Adequate renal, and bone marrow function: Leukocytes greater than or equal to 3,000/uL; Absolute neutrophil count greater than or equal to 1,500/uL; Platelets greater than or equal to 100,000/U1; Serum creatinine less than or equal to 2.0-mg/dL and urine protein: creatinine ratio less than or equal to 1.0 at screening
6. Hepatic function (endoscopic or percutaneous drainage as needed) Total bilirubin less than or equal to 2 X institutional upper limits of normal (ULN); AST (SGOT)/ALT (SGPT) less than or equal to 5 X institutional ULN
7. Patients must have no fever or evidence of infection or other coexisting medical condition that would preclude protocol therapy.
8. Pregnant women with a positive (blood B-HCG) pregnancy test are excluded from this study; women of childbearing potential (defined as those who have not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months) must agree to practice adequate contraception and to refrain from breast feeding, as specified in the informed consent.
9. Patients must sign a study-specific consent form.

Exclusion Criteria:

1. Tumors in the body or tail of the pancreas (to the left of the portal -SMV confluence) are not eligible.
2. Patients with uncontrolled hypertension, baseline blood pressure of greater than 150/100 mmHg
3. Unstable angina or New York Heart Association (NYHA) Grade II or greater congestive heart failure.
4. History of myocardial infarction, stroke, DVT, or pulmonary embolism within 6 months of the study
5. Clinically significant peripheral vascular disease.
6. Known history of bleeding diathesis coagulopathy. If patient has prior documented PT, INR then INR should be less than 2.0 (patients on anticoagulation for atrial fibrillation, other cardiac disorders, and for remote history of thrombosis are not excluded). Lab results should be within 2 weeks of patient enrollment.
7. Known presence of central nervous system or brain metastases.
8. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
9. Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0
10. Urine protein: creatinine ratio greater than 1.0 at screening; a 24 hour urine protein should be obtained and the level must be less than 1gm/24 hours in order for the patient to be eligible.
11. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
12. Serious, non-healing wound, ulcer, or bone fracture
13. Evidence of duodenal invasion
14. Inability to comply with study and/or follow-up procedures
15. Patients less than 18 years of age.