Additive effects of oral fluoropyrimidine derivative S-1 and radiation on human hypopharyngeal cancer xenografts.

The results presented here provide evidence of the enhancing effect of oral fluoropyrimidine derivative S-1 in concomitant chemoradiotherapy for head and neck cancer and further insights into its biological mechanism. To investigate the additive effect of S-1 and radiation for human hypopharyngeal cancer. Nude mice bearing hypopharyngeal cancer cells (H891) were used for an in vivo model. S-1 was administered at a volume of 0.01 mg/g body weight per mouse for 14 days, and tumors were irradiated with 2.0 Gy on days 1 and 8. Mice treated with either radiation or S-1 alone were used as controls. The growth of tumors in each group was measured and, after completion of the treatment, a focused DNA array was used to determine mRNA expression levels in the tumors of 132 genes related to 5-fluorouracil (5-FU), radiation or carcinogenesis. The additive antitumor effect of S-1 and radiation was statistically confirmed on day 14 (p=0.01). DNA array assay showed significant changes in expression of several genes, including DNA repair gene POLD, angiogenesis-related genes bFGF and TP, DNA topoisomerase TOP2A, and nucleoside transporter gene ENT1.