Tegafur is a

chemotherapeutic 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. Chemotherap ...

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

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, pancrea ...

(5-FU) used in the treatment of cancers. It is a component of the combination drug

tegafur/uracil Tegafur/uracil is a chemotherapy drug combination used in the treatment of cancer, primarily bowel cancer. It is also called UFT or UFUR. Description UFT is a first generation dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine dr ...

. When metabolised, it becomes 5-FU. It was patented in 1967 and approved for medical use in 1972.

Medical uses

As a prodrug to 5-FU it is used in the treatment of the following cancers: *

Stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...

(when combined with gimeracil and oteracil) *

Breast The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues. In females, it serves as the mammary gland, which produces and secret ...

(with uracil) *

Gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although ...

Lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...

(specifically adenocarcinoma, typically with uracil) *

Colorectal The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being ...

(usually when combined with gimeracil and oteracil) *

Head and neck This article describes the anatomy of the head and neck of the human body, including the brain, bones, muscles, blood vessels, nerves, glands, nose, mouth, teeth, tongue, and throat. Structure Bones The head rests on the top part of the vertebra ...

Liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

(with uracil) *

Pancreatic The pancreas is an Organ (anatomy), organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...

It is often given in combination with drugs that alter its bioavailability and toxicity such as gimeracil, oteracil or uracil. These agents achieve this by inhibiting the 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 and ...

(uracil/gimeracil) or

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. I ...

(oteracil).

Adverse effects

The major side effects of tegafur are similar to fluorouracil and include myelosuppression, central neurotoxicity and gastrointestinal toxicity (especially diarrhoea). Gastrointestinal toxicity is the dose-limiting side effect of tegafur. Central neurotoxicity is more common with tegafur than with fluorouracil.

Pharmacogenetics

The

(DPD) enzyme is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes

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. Comm ...

, and tegafur.

Genetic variation Genetic variation is the difference in DNA among individuals or the differences between populations. The multiple sources of genetic variation include mutation and genetic recombination. Mutations are the ultimate sources of genetic variation, ...

s within the DPD gene (''DPYD'') can lead to reduced or absent DPD activity, and individuals who are

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

for these variations may have partial or complete

DPD deficiency The abbreviation DPD may stand for: Computing * Dead Peer Detection, an IPSec VPN feature * Delegated Path Discovery, a public-key query method * Densely packed decimal, a system of binary encoding for decimal digits Engineering and technology * ...

; an estimated 0.2% of individuals have complete

. Those with partial or complete DPD deficiency have a significantly increased risk of severe or even fatal drug toxicities when treated with fluoropyrimidines; examples of toxicities include

myelosuppression Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (t ...

neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...

and

hand-foot syndrome Chemotherapy-induced acral erythema, also known as palmar-plantar erythrodysesthesia or hand-foot syndrome is reddening, swelling, numbness and desquamation (skin sloughing or peeling) on palms of the hands and soles of the feet (and, occasionally ...

Mechanism of action

It is a prodrug to 5-FU, which is a

thymidylate synthase Thymidylate synthase (TS) () is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleo ...

inhibitor.

Pharmacokinetics

It is metabolised to 5-FU by

CYP2A6 Cytochrome P450 2A6 (abbreviated CYP2A6) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. CYP2A6 is the primary enzyme responsible for the oxidation of nicotine and ...

Interactive pathway map

References

{{Chemotherapeutic agents Organofluorides Prodrugs Pyrimidinediones Pyrimidine antagonists Tetrahydrofurans Fluoropyrimidines Drugs in the Soviet Union