Each year in the United States there are more than 20,000 deaths from pancreatic cancer. Gemcitabine is a cytarabine analogue that has been shown to be effective in prolonging the survival of patients with pancreatic cancer. Radiation therapy is also a mainstay in treatment of this disease. In the present study, we propose to combine gemcitabine with radiation, in the form of Pretarget RIT, to treat human pancreatic xenografts in nude mice. The rationale for this approach is that gemcitabine is a radiationpotentiating drug and hence may enhance the therapeutic response to RIT. By using Pretarget technology, exposure of the marrow to radiation and hence induction of hematologic toxicity is reduced. This is important since marrow is also the dose-limiting organ of toxicity for gemcitabine. Feasibility of combination therapy will be demonstrated in a human pancreatic carcinoma xenograft model. The goals of the study are to demonstrate that combination therapy is more effective than monotherapy at equitoxic doses or equally effective as monotherapy at less toxic doses. PROPOSED COMMERCIAL APPLICATION: Pancreatic cancer is the thirteenth most common cancer in the developed world and the ninth most common cause of cancer death. It is estimated that there were approximately 78,000 new cases of pancreatic cancer worldwide in 1998. A nontoxic agent that offers a palliative or survival advantage of three to six months is likely to be integrated into current treatment regimens. The worldwide market for drugs to treat pancreatic cancer was valued at $233 million in 1998 and is expected to increase to over $700 million by 2008.
