title: Radiosensitization by gemcitabine fixed-dose-rate infusion versus bolus injection in a pancreatic cancer model.
abstract: It has recently been shown that fixed-dose-rate (gemcitabine) infusion may be superior to bolus gemcitabine in the treatment of metastatic pancreas cancer. We wished to compare the radiosensitizing effects of fixed-dose-rate gemcitabine infusion to standard bolus injection. We measured weight loss and mouse intestinal crypt survival to determine equally toxic concentrations of gemcitabine administered through a 3-hour fixed-dose-rate infusion versus bolus injection in combination with fractionated radiation. To measure the effect of fixed-dose-rate gemcitabine infusion or bolus injection on radiosensitization, we treated mice bearing Panc-1 xenografts with equally toxic concentrations of gemcitabine (100 mg/kg fixed-dose-rate infusion or 500 mg/kg bolus injection) and fractionated radiation and monitored tumor growth. We found that 100 mg/kg gemcitabine through fixed-dose-rate infusion produced the same weight loss and intestinal crypt toxicity as the 500 mg/kg bolus injection. In nude mice bearing Panc-1 xenografts, fixed-dose-rate gemcitabine infusion produced greater radiosensitization than bolus injection with tumor doubling times of 44 +/- 5 versus 29 +/- 3 days, respectively (*P < .05). Fixed-dose-rate gemcitabine infusion produced enhanced radiosensitization without additional normal tissue toxicity compared to bolus gemcitabine injection. These data support an ongoing clinical trial using fixed-dose-rate gemcitabine infusion combined with conformal radiation in the treatment of locally advanced pancreatic cancer.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Meredith
authors.initials: M
authors.lastname: Morgan
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: El Shaikh
authors.forename: Eyad
authors.initials: E
authors.lastname: Abu-Isa
authors.forename: Mary A
authors.initials: MA
authors.lastname: Davis
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence