Excess uracil competes with 5-FU for DPD, thus inhibiting 5-FU
catabolism.
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. Tegafur is a type of
antimetabolite. 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
antiangiogenic and cytocidal performance of 5-FU, particularly in patients with over-expressed
HIF-1.
Trial results
Trials using UFT for cancer treatment include
pancreatic cancer,
colorectal cancer,[1][2]liver cancer,[3]adenocarcinoma of the lung[4] and breast cancer[5][6] 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.[1] "[P]atients appeared strongly to prefer treatment with [oral] UFT/LV over [intravenous] 5-FU/LV."[7] 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.[8] 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.[9]
Manufacturing and marketing
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.[10]
^Watanabe T, Sano M, Takashima S, 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". J. Clin. Oncol. 27 (9): 1368–74.
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 (Williston Park, N.Y.). 11 (9 Suppl 10): 128–35.
PMID9348585.
Yoshitani S, Takashima S (February 2009). "Efficacy of postoperative UFT (Tegafur/Uracil) plus PSK therapies in elderly patients with resected colorectal cancer". Cancer Biother. Radiopharm. 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 Biother. Radiopharm. 23 (4): 461–7.
doi:
10.1089/cbr.2008.0484.
PMID18771350.
Shirao K, Hoff PM, Ohtsu A, 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". J. Clin. Oncol. 22 (17): 3466–74.
doi:
10.1200/JCO.2004.05.017.
PMID15277535.
Onoyama H, Urakawa T, Sugihara 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 (in Japanese). 27 (11): 1731–5.
PMID11057325.
Matsushita A, Hanazaki K, Noike 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 (in Japanese). 30 (9): 1327–32.
PMID14518415.
Nakagawa Y, Todoroki T, Morishita Y, et al. (2008). "A long-term survivor after pancreaticoduodenectomy for metastatic undifferentiated carcinoma of an unknown primary". Hepatogastroenterology. 55 (86–87): 1557–61.
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 Chemother. Pharmacol. 60 (3): 351–6.
doi:
10.1007/s00280-006-0377-4.
PMID17111120.
S2CID29375226.