New applications of gemcitabine and future directions in the management of pancreatic cancer

Abstract

Gemcitabine has been reported to be an active agent in pancreatic cancer. Recent applications have included the use of a fixed-dose rate regimen in patients with advanced pancreatic cancer based on the observation that deoxycytidine kinase is saturated at the plasma gemcitabine concentrations achieved with standard infusion, thereby limiting the accumulation of intracellular gemcitabine triphosphate. In a Phase II study, this regimen was associated with survival rates better than those typically observed in patients with advanced disease. Gemcitabine also has been assessed as a radiosensitizer in locally advanced cancer and although toxicity was significant, objective responses were observed and included tumor response, which permitted curative resection. Future directions in therapy for pancreatic cancer include the development of agents targeting signal transduction pathways and nuclear transcription factors based on the continually improving understanding of the role of molecular events in carcinogenesis.