Doxifluridine is a second generation nucleoside

analog Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analog ...

prodrug developed by Roche and used as a cytostatic agent in

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothe ...

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 Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pan ...

(5-FU), 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 (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 Capecitabine, sold under the brand name Xeloda among others, is a chemotherapy medication used to treat breast cancer, gastric cancer and colorectal cancer. For breast cancer it is often used together with docetaxel. It is taken by mouth. Com ...

. 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

Doxifluridine is sold under many brand names:

References

{{reflist, 30em Antineoplastic drugs Nucleosides Organofluorides Fluoropyrimidines