BACKGROUND: Pancreatic adenocarcinoma is the fourth most common cause of adult cancer death. About 50% of patients present with metastatic disease, 20% with resectable disease and the remaining 30% of patients are diagnosed with incurable, locally advanced unresectable but nonmetastatic pancreatic cancer.OBJECTIVES: To evaluate the current evidence regarding treatment of incurable, locally advanced, unresectable but nonmetastatic pancreatic cancer and produce an evidence-based practice guideline.METHODS: A systematic review of the literature was performed. The MEDLINE, CANCERLIT, and Cochrane Library databases were searched using the following medical subject heading search terms: ‘pancreatic neoplasms’, ‘chemotherapy, adjuvant’, ‘radiotherapy’, ‘immunotherapy’, combined with the text words: ‘chemotherapy’, ‘radiotherapy’, ‘radiation’, ‘immunotherapy’, combined with terms for the following study designs or publication types: practice guidelines, meta-analyses and randomized controlled trials. The Physician Data Query clinical trials database and the proceedings of the annual meetings of the American Society of Clinical Oncology (1996 to 2001) and the American Society for Therapeutic Radiology and Oncology (1999 to 2001) were searched for reports of new or ongoing trials. Relevant literature was selected and reviewed independently, and the reference lists from these sources were searched for additional trials. Interpretation of evidence was resolved by consensus.RESULTS: Eight randomized trials were obtained that met the inclusion criteria.CONCLUSIONS: Recommendations are to offer combined chemotherapy and radiotherapy to suitable patients. The preferred chemotherapeutic agent to combine with radiotherapy is bolus or infusional 5-fluorouracil, but the optimal mode and duration of 5-fluorouracil delivery is unclear. Chemotherapy alone with gem-citabine is an acceptable alternative.