Enhancement of antitumor activity of 5′-deoxy-5-fluorouridine (Furtulon®) by taxane in human gastric cancer xenografts

5'-deoxy-5-fluorouridine (5'-DFLTR, Furtulon (R)) is activated to 5-fluorouracil (5-FU) by thymidine phosphorylase (dThdPase) highly expressed in many types of tumors. In previous studies, we demonstrated that taxanes (paclitaxel or docetaxel) up-regulated the tumor levels of dThdPase and enhanced the efficacy of 5'-DFUR in human colon and mammary xenograft models. In the present study, combination therapy of 5'-DFUR with taxanes in human gastric cancer xenograft models also showed, at the least, additive antitumor activity without significant augmentation of toxicity. Furthermore, paclitaxel up-regulated dThdPase expression in the tumor tissues as confirmed with ELISA and immunohistochemistry. These results suggest taxanes would potentiate the efficacy of 5'-DFUR by up-regulating the tumor levels of dThdPase in gastric xenograft models. Clinical trials of 5'-DFUR in combination with taxane against gastric cancer are warranted.