Chemotherapy for advanced pancreatic cancer: past, present, and future

Advanced pancreatic cancer is a devastating illness characterized by significant morbidity and a brief median survival. Although standard chemotherapy with gemcitabine achieves only modest improvements in survival and quality of life, classic cytotoxic agents, such as 5-fluorouracil, pemetrexed, irinotecan, exatecan, cisplatin, or oxaliplatin, given alone or in combination with gemcitabine, have not proved superior. Thus, more recent trials have focused on targeting the biologic characteristics of pancreatic cancer. Although phase III trials of farnesyl transferase and matrix metalloproteinase inhibitors have not improved survival, encouraging preliminary results have been observed in phase II studies of inhibitors of the vascular endothelial growth factor and the epidermal growth factor receptor.