Experimental and Clinical Therapeutics

Monday, October 17, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP103) Radiosensitization of hepatic cancers by the combination of gemcitabine and fluorodeoxyuridine.

Davis, Mary*,1, Lawrence, Theodore1, 1 Radiation Oncology, Ann Arbor, MI

ABSTRACT- Unresectable primary liver cancer and colon cancer metastatic to the liver are presently treated at the University of Michigan with a combination of regional infusion of FdUrd and high dose focal radiation. This approach has produced median survivals in the range of 18 months. In order to improve further the results of treatment, we have begun to investigate the addition of gemcitabine, a potent radiosensitzer, to FdUrd and radiation in the treatment of both colon cancer metastatic to the liver and for primary liver cancer. We found in HT29 cells that the addition of gemcitabine for two hours at the beginning of a 24-h exposure to a low concentration of FdUrd (10 nM) resulted in an increase in the cytoxicity of that low dose. However, the cytotoxicity resulting from exposure to 100 nM FdUrd was not increased by gemcitabine. We found that addition of gemcitabine to 100 nM FdUrd treatment resulted in a modest increase in the radiosensitization derived from treatment with either drug alone (Radiation enhancement ratio: FdUrd (1.45+/-.07), gemcitabine (1.72+/-.14), FdUrd + gemcitabine (1.92+/.19). Initial studies with the 7721 primary hepatic cancer cell line have suggested that gemcitabine can radiosensitize these cancers (Radiation enhancement ratio of approximately 1.4 with a 2-h exposure to 300 nM gemcitabine). These data suggest that the addition of gemcitabine to FdUrd/radiation may provide some additional radiosensitization in colon cancer metastatic to the liver and that gemcitabine might be a useful radiosensitizing agent in primary liver cancer. Supported by NIH grant 5 R01 CA078554-07.

Key words: hepatic cancer, radiosensitization, gemcitabine, fluorodeoxyuridine

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2005 RRS