Tegafur/uracil is a

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 ...

drug combination used in the treatment of cancer, primarily

bowel cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowe ...

. It is also called UFT or UFUR.

Description

UFT is a first generation

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 ...

(DPD) inhibitory fluoropyrimidine drug. It is an oral agent which combines

uracil Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced ...

, a

competitive inhibitor Competitive inhibition is interruption of a chemical pathway owing to one chemical substance inhibiting the effect of another by competing with it for binding or bonding. Any metabolic or chemical messenger system can potentially be affected b ...

of DPD, with the

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) prodrug

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 ...

in a 4:1 molar ratio.

Mechanism of action

Excess uracil competes with 5-FU for DPD, thus inhibiting 5-FU

catabolism Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids ...

. The tegafur is taken up by the cancer cells and breaks down into 5-FU, a substance that kills tumor cells. The

causes higher amounts of 5-FU to stay inside the cells and kill them. Tegafur is a type of

antimetabolite An antimetabolite is a chemical that inhibits the use of a metabolite, which is another chemical that is part of normal metabolism. Such substances are often similar in structure to the metabolite that they interfere with, such as the antifolate ...

. Uracil has also been stated to help protect the gastrointestinal tract from 5-FU toxicity and the related metabolites, with less side effects than 5-FU and other 5-FU related (pro)drugs.

Tetrahydrofuran Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water- miscible organic liquid with low viscosity. It is ...

metabolites from the tegafur metabolism, unique among 5-FU based drugs, have also been shown to improve the

antiangiogenic An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical d ...

and cytocidal performance of 5-FU, particularly in patients with over-expressed

HIF-1 Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia. They are only present in parahoxozoan animals. Discovery The HIF transcriptional complex w ...

Trial results

Trials using UFT for cancer treatment include

pancreatic cancer Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a mass. These cancerous cells have the ability to invade other parts of the body. A number of types of panc ...

, colorectal cancer,

liver cancer Liver cancer (also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy) is cancer that starts in the liver. Liver cancer can be primary (starts in liver) or secondary (meaning cancer which has spread from elsewhere to th ...

adenocarcinoma Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) (AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, o ...

of the lung and breast cancer with significant gains over existing treatments, with reduced side effects, improved quality of life, improved disease free survival and/or overall survival.

History

The UFT combination was developed in Japan during the 1980s. UFT is approved in over 50 countries as a cancer therapy, most commonly for advanced colorectal cancer to replace 5FU, and has a low cost. " tients appeared strongly to prefer treatment with ralUFT/LV over ntravenous5-FU/LV." In Japan, UFT is approved for cancer treatments including tumors of the colon/rectum, lung, breast, stomach, head and neck, liver, gallbladder, bile duct, pancreas, bladder, prostate, and cervix. In the UK, tegafur/uracil with

folinic acid Folinic acid, also known as leucovorin, is a medication used to decrease the toxic effects of methotrexate and pyrimethamine. It is also used in combination with 5-fluorouracil to treat colorectal cancer and pancreatic cancer, may be used to ...

is approved as first line treatment by the

National Institute for Health and Clinical Excellence The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body of the Department of Health and Social Care in England that publishes guidelines in four areas: * the use of health technologies within ...

(NICE) for metastatic colorectal cancer.

Manufacturing and marketing

Tegafur/uracil is marketed by companies including

Merck Serono Merck Serono (EMD Serono in the United States and Canada) is a pharmaceutical company headquartered in Darmstadt, Germany, and a brand and division of Merck focused on biopharmaceuticals. In September 2006, Merck KGaA announced its intent to ...

, Korea United and Jeil, Taiho, mostly in Asia, Europe, South America, Central America and South Africa. It is made by various manufacturers and sold under a variety of names including: Tegafur-uracil, UFT, Ftorafur, Tefudex, Ufur and Uftoral. The UFT brand version is authorized for marketing in over 50 countries. Between 1984 and 2006, over 30 million patients were treated with UFT.Merck at ASCO 2007: New Data Demonstrate the Value of UFT as an Important Treatment Option for Patients With Metastatic Colorectal Cancer
June 2007, Merck's press-release

References

External links

* * * * * * * * * * * * {{refend Combination drugs Pyrimidine antagonists Merck brands