Interaction of Tomudex with radiation in vitro and in vivo

Beverly A. Teicher, Gulshan Ara, Ying Nan Chen, Abram Recht, C. Norman Coleman

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)437-442
Number of pages6
JournalInternational journal of oncology
Volume13
Issue number3
StatePublished - Sep 1 1998

Keywords

  • Colon carcinoma cells
  • Head and neck squamous carcinoma cells
  • Thymidylate synthase inhibitor
  • Tomudex

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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