Tegafur/uracil (abbreviation: UFT) is a

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

drug combination used in the treatment of cancer, primarily bowel cancer. UFT is an oral formulation combining

uracil Uracil () (nucleoside#List of nucleosides and corresponding nucleobases, symbol U or Ura) is one of the four nucleotide bases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via ...

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 ...

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

), and tegafur (a bioavailable 5-fluorouracil (5-FU)

prodrug A prodrug is a pharmacologically inactive 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 ...

) in a 4:1 molar ratio. 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.

Pharmacology

Pharmacodynamics

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 of tegafur have been shown to exhibit antiangiogenic effects and improve cytocidal performance of 5-FU, particularly in patients with over-expressed HIF-1.

Pharmacokinetics

5-FU exhibits poor intestinal penetration and significant intestinal and hepatic

first-pass metabolism The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism at a specific location in the body which leads to a reduction in the concentration of the active drug before it reaches the ...

by DPD, resulting in low and erratic systemic bioavailibility as well as formation of toxic metabolites. Tegafur, after being absorbed from the gastrointestinal tract and delivered to the liver by the

portal venous system In the circulatory system of vertebrates, a portal venous system occurs when a capillary bed pools into another capillary bed through veins, without first going through the heart. Both capillary beds and the blood vessels that connect them ar ...

, is converted to the bioactive compound 5-FU by hepatic cytochrome P450 enzymes. Meanwhile, the surplus of uracil competitively inhibits hepatic DPD, preventing immediate inactivation of the just formed 5-FU.

Clinical trials

Trials using UFT for cancer treatment include

pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...

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 in which the cancer starts in the liver, or it can be liver metastasis, or secondar ...

, adenocarcinoma of the lung, and breast cancer, with significant gains over existing treatments, including 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 (NICE) for metastatic colorectal cancer.

Available forms

Tegafur/uracil is marketed by companies including Merck Serono, 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