Dihydropyrimidine dehydrogenase activity in urothelial cancer--influence of UFT administration on DPD activity
Yano, A.; Hashimoto, K.; Okuchi, T.; Mizoguchi, H.; Mutaguchi, K.; Nakamoto, T.; Usui, T.
Gan to Kagaku Ryoho. Cancer and ChemoTherapy 28(12): 1877-1883
2001
ISSN/ISBN: 0385-0684 PMID: 11729480 Document Number: 534205
We measured the dihydropyrimidine dehydrogenase (DPD) activity considered to regulate the sensitivity of pyrimidine fluoride anti-cancer drugs in 50 cases of urothelial cancer (preoperative therapy group 10 cases, non-therapy group 40 cases). The association of DPD activity with pathological factors and TS activity as well as the influence of UFT oral administration on the DPD activity in tumors and blood were studied. The DPD activity in cancer tissue tended to be higher than that in the mucous membranes of the non-tumor region, but the difference was not significant. The DPD activity was high in infiltrative cancer (p < 0.05) but was not associated with atypia. The TS activity and DPD activity were manifested independently. The DPD activity in cancer tissue was significantly higher after UFT administration, with levels of 76.7 +/- 71.0 pmol/mg/min before administration and 220.6 +/- 129.1 pmol/mg/min after (p < 0.05). The DPD activity in peripheral blood was elevated after administration, but no significant difference was found. Since DPD activity is found in urothelial cancer tissue, 5-FU stable to DPD should preferably be used. It is also suggested that using a more potent DPD inhibitor in combination will produce higher anti-tumor effects.