Tegafur-uracil
Encyclopedia
Tegafur-uracil is a chemotherapy
drug used in the treatment of cancer, primarily bowel cancer. It is also called UFT
or UFUR.
(NICE) for metastatic colorectal cancer.
) Inhibitory Flouropyrimidine drug.
UFT is an oral agent with combines uracil
, a competitive inhibitor of DPD, with
the 5-FU prodrug tegafur
in a 4:1 molar ratio.
.
The tegafur is taken up by the cancer cells and breaks down into 5-FU, a substance that kills tumor cells. The uracil
causes higher amounts of 5-FU to stay inside the cells and kill them. Ftorafur is a type of antimetabolite
. The 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 metabolites from the tegafur metabolism, unique among 5-FU based drugs, have also been shown to improve the antiantiogenic and cytocidal performances of 5-FU, particularly in patients with over expressed HIF-1.
(leucovrin), cimetidine
and/or Polysaccharide-K
(PSK), in trials with advanced colorectal cancer, and individual cases of refractory and recurrent solid tumors with dismal prognoses. Papers show low dose neoadjuvant treatments with UFT backbones have been successfully used up to within hours of colorectal cancer surgery. Other trials show adjuvant chemotherapy with UFT backbones have been successfully started within 24 hours of colorectal cancer surgery, although two weeks after surgery was previously standard in Japan.
UFT has been administered on a continuous daily basis for 6 to 68 months at 300-400 mg per day in divided doses (metronomic dosing), in cycles of 5 days dosed at 300 mg/m2 per day, followed by the weekend off, or in cycles of 28 days dosed at 300–600 mg/m2 per day, followed by a week off. The low side effect profile of UFT in cocktails routinely allows continuous, extended treatments of several years for recurrent, refractory, "hopeless" cases of various epithelial cancers.
, Korea United and Taiho, mostly in Asia, Europe, South America, Central America and South Africa.
It is sold under a variety of names including: Tegafur-uracil, UFT, Ftorafur, Tefudex, Ufur and Uftoral.
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
drug used in the treatment of cancer, primarily bowel cancer. It is also called UFT
UFT
UFT may stand for:*Unified field theory, a theory in physics*United Faculty of Theology in Melbourne, Victoria*United Federation of Teachers, a New York union*Universidade Federal do Tocantins, a Brazilian university...
or UFUR.
Development and regulation
The UFT combination was developed in Japan during the 1980s using tegafur, a pro-5FU drug. 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. "[P]atients appeared strongly to prefer treatment with UFT/LV over 5-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 is approved as first line treatment by the National Institute for Health and Clinical ExcellenceNational Institute for Health and Clinical Excellence
The National Institute for Health and Clinical Excellence is a special health authority of the English National Health Service , serving both English NHS and the Welsh NHS...
(NICE) for metastatic colorectal cancer.
Description
UFT is a first generation DIF, or DPD (DihydroPyrimidine DehydrogenaseDihydropyrimidine dehydrogenase
Dihydropyrimidine dehydrogenase is an enzyme that is involved in pyrimidine degradation. It is the initial and rate-limiting step in pyrimidine catabolism. It catalyzes the reduction of uracil and thymine. It is also involved in the degradation of the chemotherapeutic drugs 5-fluorouracil and...
) Inhibitory Flouropyrimidine drug.
UFT is an oral agent with combines uracil
Uracil
Uracil is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine, cytosine, and guanine. In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine.Uracil is a common and...
, a competitive inhibitor of DPD, with
the 5-FU prodrug tegafur
Tegafur
Tegafur is a chemotherapeutic fluorouracil prodrug used in the treatment of cancers. It is a component of the combination drug tegafur-uracil. When metabolized, it becomes 5-fluorouracil....
in a 4:1 molar ratio.
Mechanism of action
Excess uracil competes with 5-FU for DPD, thus inhibiting 5-FU catabolismCatabolism
Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...
.
The tegafur is taken up by the cancer cells and breaks down into 5-FU, a substance that kills tumor cells. The uracil
Uracil
Uracil is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine, cytosine, and guanine. In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine.Uracil is a common and...
causes higher amounts of 5-FU to stay inside the cells and kill them. Ftorafur is a type of antimetabolite
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 antifolates that interfere with the use of folic acid...
. The 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 metabolites from the tegafur metabolism, unique among 5-FU based drugs, have also been shown to improve the antiantiogenic and cytocidal performances of 5-FU, particularly in patients with over expressed HIF-1.
Trial results
Trials using UFT for cancer treatment include pancreatic cancer, colorectal cancer, liver cancer, adenocarcinoma 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. In Japan, China and Korea, papers cite improved success utilizing UFT with folinic acidFolinic acid
Folinic acid or leucovorin , generally administered as calcium or sodium folinate , is an adjuvant used in cancer chemotherapy involving the drug methotrexate. It is also used in synergistic combination with the chemotherapy agent 5-fluorouracil.Levofolinic acid and its salts are the enantiopure...
(leucovrin), cimetidine
Cimetidine
Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
and/or Polysaccharide-K
Polysaccharide-K
Polysaccharide-K is a protein-bound polysaccharide, which is used as an immune system boosting agent in the treatment of cancer in some countries in Europe as well as China and Japan. In Japan, PSK is approved as an adjuvant for cancer therapy and is covered by government health insurance...
(PSK), in trials with advanced colorectal cancer, and individual cases of refractory and recurrent solid tumors with dismal prognoses. Papers show low dose neoadjuvant treatments with UFT backbones have been successfully used up to within hours of colorectal cancer surgery. Other trials show adjuvant chemotherapy with UFT backbones have been successfully started within 24 hours of colorectal cancer surgery, although two weeks after surgery was previously standard in Japan.
UFT has been administered on a continuous daily basis for 6 to 68 months at 300-400 mg per day in divided doses (metronomic dosing), in cycles of 5 days dosed at 300 mg/m2 per day, followed by the weekend off, or in cycles of 28 days dosed at 300–600 mg/m2 per day, followed by a week off. The low side effect profile of UFT in cocktails routinely allows continuous, extended treatments of several years for recurrent, refractory, "hopeless" cases of various epithelial cancers.
Manufacturing and marketing
It is marketed by companies including Merck SeronoMerck Serono
Merck Serono is a pharmaceutical company headquartered in Geneva, Switzerland. In September 2006, Merck KGaA announced its intent to purchase the majority of Serono shares from Ernesto Bertarelli and the Bertarelli family. The Merck-Serono merger was announced on September 21, 2006...
, Korea United and Taiho, mostly in Asia, Europe, South America, Central America and South Africa.
It is sold under a variety of names including: Tegafur-uracil, UFT, Ftorafur, Tefudex, Ufur and Uftoral.