Radiation therapy with once-weekly gemcitabine in pancreatic cancer: current status of clinical trials.

Clinical trials investigating a variety of gemcitabine-based chemoradiation therapy regimens were initiated several years ago and remain under active investigation for the treatment of patients with pancreatic cancer. These trials are based, in part, on the activity of gemcitabine as a single agent in pancreatic cancer, preclinical studies that demonstrated radiosensitization, and the need for approaches with greater efficacy than that provided by 5-fluorouracil (5-FU)-based chemoradiation therapy. In this review, we describe and compare several Phase I clinical trials investigating dose escalation of once-weekly gemcitabine with concurrent radiation therapy. We also describe a relatively novel approach successfully investigating radiation dose escalation with a standard weekly dose of gemcitabine. Toxicity data from this trial, and the prior trials of gemcitabine dose escalation with more conventional radiation therapy, suggest that the volume of normal tissue radiated in gemcitabine-based chemotherapy regimens may be the most critical consideration for future trial designs. Finally, we highlight the need to fully consider the design of future trials in the context of both local and distant disease control, given the radiosensitizing potential and systemic activity of gemcitabine.