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.
Biology
5-Fluorouracil, the nucleobase of doxifluridine, is currently an FDA-approved antimetabolite. 5-FU is normally administered intravenously to prevent its degradation by dihydropyrimidine dehydrogenase in the gut wall. Doxifluridine 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 in some individuals.The most frequent adverse effects for doxifluridine were neurotoxicity and mucositis.
Brand names
Doxifluridine is sold under many brand names:| Brand name | Company | Country |
| Didox | Shin Poong Pharm. Co., Ltd. | South Korea |
| Doxyfluridine | Kwang Dong | South Korea |
| Doxifluridine cap | Myungmoon Pharma Co. Ltd. | South Korea |
| Ai Feng | Hengrui | China and Japan |
| Doxifluridine | XinShiDai Pharmaceutical | China and Japan |
| Furtulon | Roche, Chugai | China and Japan |
| Ke Fu | Zhaohui | China and Japan |
| Ke Tuo | Southwest | China and Japan |
| Qi Nuo Bi Tong | Wanjie High-Tech | China and Japan |
| Shu Qi | Team | China and Japan |
| Tan Nuo | Xinchang Medicine & Chemical Co Ltd | China and Japan |
| Yi Di An | Pacific | China and Japan |