Tegafur/gimeracil/oteracil, sold under the brand names Teysuno and TS-1, is a fixed-dose

combination medication A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC prod ...

used for the treatment of advanced gastric cancer when used in combination with

cisplatin Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, ...

, and also for the treatment of head and neck cancer, colorectal cancer, non–small-cell lung, breast, pancreatic, and biliary tract cancers. The most common severe side effects when used in combination with cisplatin include neutropenia (low levels of neutrophils, a type of white blood cell), anaemia (low red blood cell counts) and fatigue (tiredness). Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Tegafur/gimeracil/oteracil (Teysuno) was approved for medical use in the European Union in March 2011. It has not been approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA).

Medical uses

In the European Union tegafur/gimeracil/oteracil is indicated in adults for the treatment of advanced gastric cancer when given in combination with cisplatin.

Contraindications

In the European Union, tegafur/gimeracil/oteracil must not be used in the following groups: * people receiving another fluoropyrimidine (a group of anticancer medicines that includes tegafur/gimeracil/oteracil) or who have had severe and unexpected reactions to fluoropyrimidine therapy; * people known to have no DPD enzyme activity, as well as people who, within the previous four weeks, have been treated with a medicine that blocks this enzyme; * pregnant or breastfeeding women; * people with severe leucopenia, neutropenia, or thrombocytopenia (low levels of white cells or platelets in the blood); * people with severe kidney problems requiring dialysis; * people who should not be receiving cisplatin.

Mechanism of action

Tegafur Tegafur is a chemotherapeutic prodrug of 5-fluorouracil (5-FU) used in the treatment of cancers. It is a component of the combination drug tegafur/uracil. When metabolised, it becomes 5-FU. It was patented in 1967 and approved for medical use ...

is the actual chemotherapeutic agent. It is a prodrug of the active substance

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). Tegafur, is a cytotoxic medicine (a medicine that kills rapidly dividing cells, such as cancer cells) that belongs to the ‘anti-metabolites’ group. Tegafur is converted to the medicine fluorouracil in the body, but more is converted in tumor cells than in normal tissues. Fluorouracil is very similar to pyrimidine. Pyrimidine is part of the genetic material of cells (DNA and RNA). In the body, fluorouracil takes the place of pyrimidine and interferes with the enzymes involved in making new DNA. As a result, it prevents the growth of tumor cells and eventually kills them. Gimeracil inhibits the degradation of fluorouracil by reversibly blocking the

dehydrogenase A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as ...

enzyme

dihydropyrimidine dehydrogenase In enzymology, a dihydropyrimidine dehydrogenase (NADP+) () is an enzyme that catalyzes the chemical reaction :5,6-dihydrouracil + NADP+ \rightleftharpoons uracil + NADPH + H+ Thus, the two substrates of this enzyme are 5,6-dihydrouracil an ...

(DPD). This results in higher 5-FU levels and a prolonged half-life of the substance. Oteracil mainly stays in the gut because of its low permeability, where it reduces the production of 5-FU by blocking the enzyme

orotate phosphoribosyltransferase Orotate phosphoribosyltransferase (OPRTase) or orotic acid phosphoribosyltransferase is an enzyme involved in pyrimidine biosynthesis. It catalyzes the formation of orotidine 5'-monophosphate (OMP) from orotate and phosphoribosyl pyrophosphate. ...

. Lower 5-FU levels in the gut result in a lower gastrointestinal toxicity. Within the medication, the molar ratio of the three components (tegafur:gimeracil:oteracil) is 1:1:0.4. The

maximum tolerated dose The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug. It is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes ...

differed between Asian and Caucasian populations (80 mg/m2 and 25 mg/m2 respectively), perhaps due to differences in CYP2A6 genotype.

Research

It is being developed for the treatment of hepatocellular carcinoma. and has activity in esophageal,(Perry Chapter 33) breast, cervical, and colorectal cancer. File:Tegafur.png, Tegafur File:Gimeracil skeletal.svg, Gimeracil File:Oteracil skeletal.svg, Oteracil potassium

References

External links

* * * {{DEFAULTSORT:Tegafur Gimeracil Oteracil Antineoplastic drugs Combination drugs Pyrimidine antagonists Taiho Pharmaceutical