Pancreatic cancer is a major health problem in the United States and other developed nations. Approximately thirty thousand cases of adenocarcinoma of the exocrine pancreas are diagnosed in the United States each year. The majority of these tumors are unresectable at the time of diagnosis. Unresectable and metastatic pancreatic cancer is often resistant to treatment with response rates of less than 10% and median survival times of less than six months associated with single agent chemotherapy. As of July 2003, gemcitabine remains the standard of care palliative chemotherapy for patients with locally advanced or metastatic pancreatic cancer. This drug has modest clinical activity. In a phase III randomized controlled trial, 126 patients with advanced symptomatic pancreatic cancer were randomized to receive either gemcitabine 1000 mg/m2 weekly x 7 followed by a week of rest and then weekly x 3 every 4 weeks thereafter or fluorouracil 600 mg/m2 once weekly. The primary endpoint was a score of clinical benefit response (CBR) derived from a composite of pain, performance status, and weight. CBR was experienced by 24% of the gemcitabine treated patients compared with 5% of 5-FU treated patients. The median survival durations were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients, respectively. The one year survival was 18% for patients treated with gemcitabine compared to 2% for patients treated with 5-FU. The effectiveness of gemcitabine may be improved by altering the standard infusion schedule to a fixed dose rate. Gemcitabine requires intracellular phosphorylation to form active di- and triphosphates, which is dose rate dependent. A phase II trial randomized patients to either receive gemcitabine 2200 mg/m2 over a standard 30 minute infusion or gemcitabine 1500 mg/m2 at a fixed rate of 10 mg/m2/min weekly x 3 every 4 weeks. The fixed rate infusion of 10 mg/m2/min was associated with a higher response rate of 16.6% v 2.7%, longer median survival 6.1 v 4.7 months, and a higher percentage of patients surviving one year or more, 23% v 0%. The fixed rate infusion schedule was also associated with significantly higher median gemcitabine triphosphate levels in peripheral circulating mononuclear cells after each infusion.