Tegafur

(BAN, USAN, rINN)
Tegafur Chemical formula
Synonyms: FT-207; Ftorafur; MJF-12264; NSC-148958; Tégafur; Tegafurum; Tegafuuri; WR-220066. 5-Fluoro-1-(tetrahydro-2-furyl)uracil; 5Fluoro-1-(tetrahydro-2-furyl)pyrimidine-2,4(1H,3H)-dione.
Cyrillic synonym: Тегафур.

💊 Chemical information

Chemical formula: C8H9FN2O3 = 200.2.
CAS — 17902-23-7.
ATC — L01BC03.
ATC Vet — QL01BC03.

Pharmacopoeias.

In Chin. and Jpn.

💊 Adverse Effects, Treatment, and Precautions

As for Fluorouracil. Bone-marrow depression may be less severe with tegafur but gastrointestinal toxicity is often dose-limiting and central neurotoxicity is more common. Peripheral oedema and dyspnoea occur commonly. Increases in liver function test values are common and there are reports of fatal fulminant hepatitis. Liver function should be monitored in patients with hepatic impairment given tegafur; it should not be given in severe hepatic impairment.

💊 Interactions

Tegafur should not be used with drugs that inhibit dihydropyrimidine dehydrogenase; fatalities have occurred in patients given tegafur and sorivudine. Increased plasma concentrations of phenytoin, and symptoms of toxicity during use with tegafur and uracil, have been reported.

💊 Pharmacokinetics

Tegafur is well absorbed from the gastrointestinal tract after oral doses. After an intravenous dose it is reported to have a prolonged plasma half-life of 6 to 16 hours. Tegafur appears to be slowly metabolised in the liver to fluorouracil, and some intracellular conversion to fluorouracil may also occur. Tegafur crosses the blood-brain barrier and is found in the CSF.
1. Etienne-Grimaldi M-C, et al. A clinical pharmacokinetic analysis of tegafur-uracil (UFT) plus leucovorin given in a new twicedaily oral administration schedule. Clin Pharmacokinet 2007; 46: 953–63.

💊 Uses and Administration

Tegafur is considered to be an orally active prodrug of fluorouracil. It has been used in the management of malignant neoplasms including those of the breast, gallbladder, gastrointestinal tract, head and neck, liver, and pancreas. Tegafur has been given orally in doses up to 1 g/m2 daily. It is often given with uracil. Tegafur 300 mg/m2 daily, with uracil 672 mg/m2 daily, may be given in 3 divided oral doses, together with calcium folinate, in the management of metastatic colorectal cancer. Doses are given for a cycle of 28 days, followed by 7 days without treatment. The drugs should be taken 1 hour before or after meals, and doses modified according to toxicity. Doses of tegafur 1 to 3 g/m2 daily for 5 days have been given intravenously.

Administration.

Tegafur is an orally active prodrug of fluorouracil. Although it has been given as a single agent, it is more often used with drugs that modify its bioavailability and toxicity.1 These include uracil and gimestat (5-chlorodihydropyrimidine, CDHP), which can increase fluorouracil concentrations by inhibition of dihydropyrimidine dehydrogenase, the enzyme responsible for its further catabolism,1-3 and oxonic acid (otastat), which inhibits another enzyme, orotate pyrimidine phosphoribosyl transferase, thought to play a role in the gastrointestinal toxicity of fluorouracil and its prodrugs.2 UFT consists of tegafur and uracil in the optimal molar ratio 1:4.1It is available for the treatment of colorectal cancer—for doses, see above. A preliminary analysis of a large study comparing oral UFT and calcium folinate therapy with intravenous fluorouracil and calcium folinate found both regimens to be well tolerated with similar levels of toxicity.4 Adjuvant therapy with UFT appears to improve survival in patients with adenocarcinoma of the lung5 and node-negative breast cancer.6 S-1 (TS-1, Taiho Jpn) is a combination of tegafur, gimestat and the potassium salt of oxonic acid in the molar ratio 10:4:10. It has been tried in gastric and colorectal cancers,2,3,7,8 and initial results have suggested comparable activity to fluorouracil and calcium folinate in induction regimens, but the incidence of diarrhoea and stomatitis was reduced.
1. Adjei AA. A review of the pharmacology and clinical activity of new chemotherapy agents for the treatment of colorectal cancer. Br J Clin Pharmacol 1999; 48: 265–77
2. Sakata Y, et al. Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients. Eur J Cancer 1998; 34: 1715–20
3. Sugimachi K, et al. An early phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. Oncology 1999; 57: 202–10
4. Smith R, et al. UFT plus calcium folinate vs 5-FU plus calcium folinate in colon cancer. Oncology (Huntingt) 1999; 13 (suppl 3): 44–7
5. Kato H, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med 2004; 350: 1713–21
6. Noguchi S, et al. Postoperative adjuvant therapy with tamoxifen, tegafur plus uracil, or both in women with node-negative breast cancer: a pooled analysis of six randomized controlled trials. J Clin Oncol 2005; 23: 2172–84
7. Osugi H, et al. Oral fluoropyrimidine anticancer drug TS-1 for gastric cancer patients with peritoneal dissemination. Oncol Rep 2002; 9: 811–15
8. Shibahara K, et al. Retrospective study of S-1 versus tegafur/uracil and oral leucovorin in patients with metastatic colorectal cancer. Anticancer Res 2008; 28: 1779–83.

💊 Preparations

Proprietary Preparations

Cz.: Ftorafur; UFT; Hong Kong: Futraful; Hung.: Ftorafur; Indon.: Futraful; Ital.: Citofur†; Jpn: Futraful; Rus.: Ftorafur (Фторафур); Spain: Utefos; Thai.: UFUR. Multi-ingredient: Arg.: Asofurtal; UFT; Austria: UFT; Belg.: UFT; Braz.: UFT; Denm.: Uftoral; Fr.: UFT; Ger.: UFT; Gr.: UFT; Hong Kong: UFT; Hung.: UFT; Israel: UFT†; Ital.: UFT; Jpn: UFT; Malaysia: UFT; Mex.: UFT; Neth.: UFT; Norw.: UFT; NZ: Orzel†; Philipp.: Tefudex; UFT; Port.: UFT; Rus.: UFT (УФТ); S.Afr.: UFT; Singapore: UFT; Spain: UFT; Swed.: UFT; Thai.: UFT; Turk.: UFT; UK: Uftoral.
Published February 27, 2019.