Chemotherapy for advanced pancreatic cancer

Achieving substantial and meaningful improvements in the response and survival rates for advanced pancreatic cancer has proved to be an elusive goal for many years. 5-Fluorouracil (5-FU)-based chemotherapy has typically produced discouraging response rates or improved clinical benefit for patients, and attempts to improve these results by altering 5-FU dosages, administration schedules, or using a variety of drugs in combination with 5-FU have been unrewarding. A clinical benefit, however, was identified when gemcitabine first generated improvements in symptom control in patients with advanced disease. In a subsequent randomized trial, gemcitabine demonstrated superiority to 5-FU with respect to response rate, time to progression, and median survival. These improvements were also associated with improvement in clinical benefit. The findings of subsequent randomized Phase III trials have suggested a survival benefit for gemcitabine compared with several single agents or combinations. Gemcitabine has thus become the de facto standard of care for advanced pancreatic cancer, and current efforts are directed toward finding strategies that can capitalize on and extend these clinical benefits.