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Radiosensitization By Gemcitabine Fixed-Dose-Rate Infusion Versus Bolus Injection in a Pancreatic Cancer Model
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 a...
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Published in: | Translational oncology 2008-03, Vol.1 (1), p.44-49 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 1936-5233 1936-5233 |
DOI: | 10.1593/tlo.07118 |