Pancreatic cancer--is the wall crumbling?

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, more so with the recent negative results of several much anticipated randomized trials. Gemcitabine 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 (5-FU). Since then, clinical trials have explored the pharmacokinetic modulation of gemcitabine by fixed dose administration and the combination of gemcitabine with other cytotoxics or the biological 'targeted' agents. Against a background of numerous negative randomized trials of gemcitabine-based combination treatment, two trials have recently reported modest survival improvements with the use of combination treatment: the United Kingdom National Cancer Research GEMCAP trial of gemcitabine with the orally administered precursor of 5-FU-capecitabine and the National Cancer Institute of Canada Clinical Trials Group PA.3 trial in which the tyrosine kinase inhibitor erlotinib was used with gemcitabine. This review will summarize the results of several recent randomized trials of combination treatment in advanced pancreatic cancer and discuss their implications for clinical practice and for future research in this disease.