Recent developments in palliative chemotherapy for locally advanced and metastatic pancreas cancer.

In spite of advances made in the management of the other more common cancers of the gastrointestinal tract, significant progress in the treatment of pancreatic cancer remains elusive. Nearly as many deaths occur from pancreatic cancer as are diagnosed each year reflecting the poor prognosis typically associated with this disease. Until recently, the only treatment with an impact on survival was surgery. In the palliative setting, gemcitabine (Gem) has been a standard treatment for advanced pancreatic cancer since it was shown a decade ago to result in a superior clinical benefit response and survival compared with bolus 5-fluorouracil. Since then, clinical trials have explored the pharmacokinetic modulation of Gem by fixed dose administration and the combination of Gem with other cytotoxic or the biologically "targeted" agents. However, promising trial results in small phase II trials have not translated into survival improvements in larger phase III randomized trials in the advanced disease setting. Two trials have recently reported modest survival improvements with the use of combination treatment with Gem and capecitabine (United Kingdom National Cancer Research GEMCAP trial) or erlotinib (National Cancer Institute of Canada Clinical Trials Group PA.3 trial). This review will focus on the use of systemic therapy for advanced and metastatic pancreatic cancer, summarizing the results of several recent clinical trials and discuss their implications for clinical practice. We will also discuss briefly the second-line chemotherapy options for advanced pancreatic cancer.