INTERACTION OF TOMUDEX WITH RADIATION IN-VITRO AND IN-VIVO

The potential of the thymidylate synthase inhibitor, Tomudex to intera ct with ionizing radiation was assessed in vitro and in vivo in compar ison with 5-fluorouracil. A concentration of 1 mu M 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 an d neck squamous carcinoma cells, resulting in enhancement ratios of 10 and 2.8 for normally oxygenated and hypoxic HT-29 cells at 5 Gray, re spectively, and enhancement ratios of 19.5 and 2.7 for normally oxygen ated and hypoxic SCC-25 cell at 5 Gray, respectively. Two schedules of Tomudex administered to animals bearing the Lewis lung carcinoma resu lted in additive tumor growth delay with the fractionated radiation th erapy. In nude mice bearing the HT-29 colon carcinoma grown as a xenog raft, administration of Tomudex daily for 5 days on a 1 or 2-week sche dule resulted in increased tumor growth delay along with fractionated radiation therapy on the same schedules. However, administration of To mudex intermittently on a 2-week schedule appeared to be more interact ive with daily fractionated radiation therapy on the 2-week schedule. In each assay, the results obtained with Tomudex were equal to or exce eded those obtained with 5-fluorouracil. These findings indicate that clinical trial of Tomudex along with fractionated radiation therapy is warranted.