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.[citation needed]
5-FU exhibits poor intestinal penetration[3][4] and significant intestinal[5][6] and hepatic first-pass metabolism[6] by DPD, resulting in low and erratic systemic bioavailibility as well as formation of toxic metabolites.[7] Tegafur, after being absorbed from the gastrointestinal tract and delivered to the liver by the portal venous system, 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.[1]
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.[8] "[P]atients appeared strongly to prefer treatment with [oral] UFT/LV over [intravenous] 5-FU/LV."[14] 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.[15] In the UK, tegafur/uracil with folinic acid is approved as first line treatment by the National Institute for Health and Clinical Excellence (NICE) for metastatic colorectal cancer.[16]
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.[17]
^Gu J, Yuasa H, Hayashi Y, Watanabe J (August 1998). "First-pass metabolism of 5-fluorouracil in the perfused rat small intestine". Biological & Pharmaceutical Bulletin. 21 (8): 871–873. doi:10.1248/bpb.21.871. PMID9743260.
^ abYuasa H, Gu J, Hayashi Y, Watanabe J (September 1998). "First-pass metabolism of 5-fluorouracil in rats". The Journal of Pharmacy and Pharmacology. 50 (9): 1019–1025. doi:10.1111/j.2042-7158.1998.tb06917.x. PMID9811163.
^Watanabe T, Sano M, Takashima S, Kitaya T, Tokuda Y, Yoshimoto M, et al. (March 2009). "Oral uracil and tegafur compared with classic cyclophosphamide, methotrexate, fluorouracil as postoperative chemotherapy in patients with node-negative, high-risk breast cancer: National Surgical Adjuvant Study for Breast Cancer 01 Trial". Journal of Clinical Oncology. 27 (9): 1368–1374. doi:10.1200/JCO.2008.18.3939. PMID19204202.
Murad A, de Andrade CA, Delfino C, Arikian S, Doyle J, Sinha N (September 1997). "A pharmacoeconomic comparison of UFT and 5-FU chemotherapy for colorectal cancer in South America". Oncology. 11 (9 Suppl 10): 128–135. PMID9348585.
Yoshitani S, Takashima S (February 2009). "Efficacy of postoperative UFT (Tegafur/Uracil) plus PSK therapies in elderly patients with resected colorectal cancer". Cancer Biotherapy & Radiopharmaceuticals. 24 (1): 35–40. doi:10.1089/cbr.2008.0547. PMID19243246.
Sakai T, Yamashita Y, Maekawa T, Mikami K, Hoshino S, Shirakusa T (August 2008). "Immunochemotherapy with PSK and fluoropyrimidines improves long-term prognosis for curatively resected colorectal cancer". Cancer Biotherapy & Radiopharmaceuticals. 23 (4): 461–467. doi:10.1089/cbr.2008.0484. PMID18771350.
Shirao K, Hoff PM, Ohtsu A, Loehrer PJ, Hyodo I, Wadler S, et al. (September 2004). "Comparison of the efficacy, toxicity, and pharmacokinetics of a uracil/tegafur (UFT) plus oral leucovorin (LV) regimen between Japanese and American patients with advanced colorectal cancer: joint United States and Japan study of UFT/LV". Journal of Clinical Oncology. 22 (17): 3466–3474. doi:10.1200/JCO.2004.05.017. PMID15277535.
Onoyama H, Urakawa T, Sugihara S, Hashimoto Y, Azumi Y, Takao S, et al. (October 2000). "[A noteworthy case of postoperative liver metastasis from gastric cancer which responded well to UFT therapy]". Gan to Kagaku Ryoho. Cancer & Chemotherapy (in Japanese). 27 (11): 1731–1735. PMID11057325.
Matsushita A, Hanazaki K, Noike T, Nakagawa K, Misawa R, Nakata T, et al. (September 2003). "[Complete disappearance with oral UFT administration of recurrent hepatocellular carcinoma of the remnant liver and multiple lung metastasis after hepatic resection]". Gan to Kagaku Ryoho. Cancer & Chemotherapy (in Japanese). 30 (9): 1327–1332. PMID14518415.
Nakagawa Y, Todoroki T, Morishita Y, Mori K, Nakahaashi C, Ohkohchi N, et al. (2008). "A long-term survivor after pancreaticoduodenectomy for metastatic undifferentiated carcinoma of an unknown primary". Hepato-Gastroenterology. 55 (86–87): 1557–1561. PMID19102342.
Lin PC, Chen WS, Chao TC, Yang SH, Tiu CM, Liu JH (August 2007). "Biweekly oxaliplatin plus 1-day infusional fluorouracil/leucovorin followed by metronomic chemotherapy with tegafur/uracil in pretreated metastatic colorectal cancer". Cancer Chemotherapy and Pharmacology. 60 (3): 351–356. doi:10.1007/s00280-006-0377-4. PMID17111120. S2CID29375226.
