Abstract
The potential of the thymidylate synthase inhibitor, Tomudex to interact with ionizing radiation was assessed in vitro and in vivo in comparison with 5-fluorouracil. A concentration of 1 μM Tomudex decreased the shoulder of the radiation survival curves for normally oxygenated and hypoxic human HT- 29 colon carcinoma cells and human SCC-25 head and neck squamous carcinoma cells, resulting in enhancement ratios of 10 and 2.8 for normally oxygenated and hypoxic HT-29 cells at 5 Gray, respectively, and enhancement ratios of 19.5 and 2.7 for normally oxygenated and hypoxic SCC-25 cell at 5 Gray, respectively. Two schedules of Tomudex administered to animals bearing the Lewis lung carcinoma resulted in additive tumor growth delay with the fractionated radiation therapy. In nude mice bearing the HT-29 colon carcinoma grown as a xenograft, administration of Tomudex daily for 5 days on a 1 or 2-week schedule resulted in increased tumor growth delay along with fractionated radiation therapy on the same schedules. However, administration of Tomudex intermittently on a 2-week schedule appeared to be more interactive with daily fractionated radiation therapy on the 2-week schedule. In each assay, the results obtained with Tomudex were equal to or exceeded those obtained with 5-fluorouracil. These findings indicate that clinical trial of Tomudex along with fractionated radiation therapy is warranted.
Original language | English (US) |
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Pages (from-to) | 437-442 |
Number of pages | 6 |
Journal | International journal of oncology |
Volume | 13 |
Issue number | 3 |
State | Published - Sep 1 1998 |
Keywords
- Colon carcinoma cells
- Head and neck squamous carcinoma cells
- Thymidylate synthase inhibitor
- Tomudex
ASJC Scopus subject areas
- Oncology
- Cancer Research