15082 Background: Locally advanced pancreas cancer (LAPD) is a therapeutic challenge for clinicians worldwide. Chemoradiation and chemotherapy-only approaches are used, typically producing overall survival (OS) of only 9–14 months (mo). In 1995, we developed a unique chemoradiation method using cisplatin (C), 5-FU (F), and alpha-interferon (IFN) , followed by post-chemoradiation (F). As adjuvant therapy to resected pancreas cancer; this method has produced 5-yr OS of 40%-50% in our institution.We report here a phase II trial assessing the efficacy of this regimen in LAPD. Methods: Patients with LAPD ( non-laparascopy-staged), ECOG performance score 0–1, were treated with XRT 5000cGy/25 fractions simultaneous with (C) 30mg/m2 d 1,8,15,22,29, (F) 200mg/m2 IVCI d 1–35, and (IFN) 3million U SQ qod d 1–35 .(F) 200mg/m2 IVCI was given for 2 additional 6 week cycles (weeks 9–14 and 17–22) . Therapy post- progression was given at the discretion of the treating physician. Results: From 7/1995 and 7/2002, 20 patients(pts) (median age 62) were accrued. 19/20 pts (95%) completed >95% of specified XRT dose; 17/20 pts (85%) received >80% of specified chemotherapy doses during XRT. 12/20 pts (60%) completed >80% of specified (F) post chemoradiation. 10/20 pts (50%) experienced grade 3 toxicity during chemoradiation, and 10/20 pts (50%) required hospitalization including 4-GI symptoms (e.g.diarrhea/dehydration), 2-GI bleeding, 2-fever, 1-hyponatremia and 1-anorexia. No grade 4 toxicities and no toxic deaths occurred. All 20 pts have now expired. Initial site of disease progression was liver 8 pts, abdominal cavity 4 pts, local 4 pts, unknown 4 pts. Median time to progression was 7 mo; median OS was 12.5 mo (range 3–51 mo). 1-and 2-yr OS were 55% and 20%, respectively. 7/20 pts. received gemcitabine-based regimens following tumor progression; median OS of these pts was 17 mo. Conclusions: 1) The IFN-based chemoradiation described above is moderately severe in toxicity, but can be successfully applied to LAPD. 2) This chemoradiation method may be a sucessful platform for the treatment of LAPD with gemcitabine-based chemotherapy. Studies investigating this approach are presently underway at our institution. No significant financial relationships to disclose.