Doxifluridine

Doxifluridine is a second generation nucleoside analog prodrug developed by Roche and used as a cytostatic agent in chemotherapy in several Asian countries including China and South Korea. Doxifluridine is not FDA-approved for use in the USA. It is currently being evaluated in several clinical trials as a stand-alone or combination therapy treatment.
Generic names.
5'-deoxy-5'-fluorouridine, 5'-deoxy-5-fluorouridine, 5'-DFUR, 5'-fluoro-5'-deoxyuridine, doxifluridine, doxyfluridine, Furtulon, Ro 21-9738
Biology.
5-fluorouracil (5-FU) is currently an FDA-approved antimetabolite. 5-FU is normally administered intravenously to prevent its degradation by dihydropyrimidine dehydrogenase in the gut wall. Doxifluridine (5´-deoxy-5-fluorouridine) is a fluoropyrimidine derivative of 5-FU, thus a second-generation nucleoside prodrug. Doxifluridine was designed to improve oral bioavailability in order to avoid dihydropyrimidine dehydrogenase degradation in the digestive system.
Within a cell, pyrimidine nucleoside phosphorylase or thymidine phosphorylase can metabolize doxifluridine into 5-FU. It is also a metabolite of capecitabine. High levels of pyrimidine-nucleoside phosphorylase and thymidine phosphorylase are expressed in esophageal, breast, cervical, pancreatic, and hepatic cancers. Liberation of 5-FU is the active metabolite and leads to inhibition of DNA synthesis and cell death.
Side effects.
High thymidine phosphorylase expression is also found in the human intestinal tract, resulting in dose-limiting toxicity (diarrhea) in some individuals.
The most frequent adverse effects for doxifluridine were neurotoxicity and mucositis.
Brand names.
Ai Feng - Hengrui, China; Didox - Shin Poong, South Korea; Doxifluridine-XinShiDai Pharm - XinShiDai Pharmaceutical, China; Doxyfluridine Kwangdong - Kwang Dong, South Korea; Furtulon - Roche, China; Ke Fu - Zhaohui, China; Ke Tuo - Southwest, China; Qi Nuo Bi Tong - Wanjie High-Tech, China; Shu Qi - Team, China; Tan Nuo- Xinchang Medicine & Chemical Co Ltd, China; Yi Di An - Pacific, China; Doxifluridine cap- Myungmoon Pharma Co. Ltd.