Thymidine phosphorylase expression correlates with malignant potential and anti-tumor effect of doxifluridine on gastric cancer: multivariate analysis for adjuvant chemotherapy doxifluridine vs. 5-fluorouracil

Abstract

Doxifluridine (5'-DFUR) is an anticancer drug converted to 5-fluorouracil (5-FU) by thymidine phosphorylase (TP). TP is an angiogenetic and platelet-derived endothelial cell growth factor. We evaluated the relation between TP expression and chemotherapeutic efficacy and prognosis for gastric cancer. Advanced gastric cancer patients given oral adjuvant chemotherapeutics either 5'-DFUR; 163 patients or 5-FU; 162 patients were examined. TP expression was assessed with immunohistochemical staining. Multivariate analysis for influencing survival was done, employing variables such as gender, age, procedure, tumor size, location, Borrmann type, histologic factors [type, depth of invasion, lymph node metastasis (n), lymphatic invasion (ly), and venous invasion (v)], drug administered, and TP expression. In the patients with serosal invasion, 5'-DFUR in TP positive was an independent prognostic factor (risk ratio, 4.450; 95% confidence limit, 2.099-9.436), indicating significantly improved prognosis over the 5-FU group. In TP negative, n and ly were independent prognostic factors, but the survival curves of the two chemotherapeutic groups were not significantly different. TP expression was not prognostic factor in 5'-DFUR group, while, in 5-FU group, TP expression was an independent prognostic factor (2.834, 1.467-5.476). In conclusion, it was suggested that TP positive gastric cancer with serosal invasion increased malignant potential of the tumor and 5'-DFUR efficacy.