Twenty consecutive patients with unresectable, locally advanced pancreatic cancer were treated with split courses of radiotherapy (RT) and simultaneous multidrug chemotherapy consisting of 5 fluorouracil, continuous infusion, streptozotocin, and cisplatin. A separate, retrospective study identified a group of 28 contemporary patients with less advanced pancreatic cancers, all of which were successfully resected. The survival rate of the two groups were similar over the first 2 years, although it initially favored the unresectable group. This pattern of survival among patients treated with combined modality therapy provides a basis for new studies. At the two clinical extremes, these include treatment of unresectable tumors previously considered ineligible for this treatment and initial treatment before resection of stage I tumors.