Chemotherapy, Interferon Alfa, and Radiation Therapy in Treating Patients Who Have Undergone Surgery For Pancreatic Cancer

Inclusion Criteria: 1. Biopsy proven completely resected (R0 or R1) pancreatic adenocarcinoma of the pancreatic head or uncinate process \[American Joint Committee on Cancer (AJCC) Stage I-III\]. Surgery (pancreaticoduodenectomy) may be performed at M. D. Anderson Cancer Center or prior to referral to M. D. Anderson Cancer Center. Protocol treatment must begin within 12 weeks of surgery. 2. Postoperative (pre-treatment) computed tomography (CT) scan without evidence of radiographically defineable residual primary/metastatic disease or clinically significant post-surgical changes. 3. Staging studies completed within three weeks +/- 3 days of protocol registration. 4. Hemoglobin (Hb) \>9.0 g/%, White Blood Count (WBC) \>3,000 cells/mm3 (Absolute neutrophil count (ANC)\>1,500 cells/mm3), platelets \>75,000 cells/mm3. 5. Postoperative serum calcium (CA) 19-9 \< 100. 6. Performance status: Zubrod 0 or 1. 7. Creatinine £1.5 mg/dL and calculated or measured creatinine clearance (CrCl) of 60 ml/min or greater by the following formula: Creatinine clearance rate (CrCl) = (140 - age) \* Weight (kg) \* 0.85 (female) OR \* 1.00 (male) 72 \* serum creatinine 8. Patients should have bilateral renal function, as determined on excretory urogram (IVP) or abdominal CT, or ³ 2/3 of one functioning kidney must be able to be shielded from the radiation beam. 9. No acute infections at the time of therapy initiation. 10. Women of childbearing potential must agree to practice adequate contraception and to refrain from breast feeding, as specified in the informed consent. 11. Patients must sign a study-specific consent form, which is attached to this protocol. 12. Patients with a prior history of non-pancreatic malignancy who are free of disease from their primary cancer may be eligible at the discretion of the study chair. Exclusion Criteria: 1. Residual (clinical or CT definable) metastatic or incompletely resected local disease. 2. Patients with positive peritoneal cytology (for adenocarcinoma) detected at laparotomy for pancreaticoduodenectomy or as part of prior laparoscopic assessment of peritoneal cytology. 3. Patients with a history of hypersensitivity to interferon alfa-2b. 4. Patients with significant cardiovascular disease, such as unstable angina or congestive heart failure. 5. Pregnancy or breastfeeding. 6. Patients with severe pulmonary disease. 7. Children under the age of 18 are excluded (as the disease is rare and toxicity profile of this regimen untested in pediatric patients). 8. Presence or history of severe depression.