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Tegafur response

MedGen UID:
338948
Concept ID:
C1852514
Finding
Synonym: TEGAFUR, POOR METABOLISM OF
Drug:
Tegafur
MedGen UID:
5286
Concept ID:
C0016778
Pharmacologic Substance
A congener of the antimetabolite fluorouracil with antineoplastic activity. Tegafur is a prodrug that is gradually converted to fluorouracil in the liver by the cytochrome P-450 enzyme. Subsequently, 5-FU is metabolized to two active metabolites, 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP) by both tumor cells and normal cells. FdUMP inhibits DNA synthesis and cell division by inhibiting thymidylate synthase and reducing normal thymidine production, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate. (NCI04) [from NCI]
 
Gene (location): DPYD (1p21.3)
 
OMIM®: 122720

Definition

Tegafur is a chemotherapeutic agent and a member of the fluoropyrimidine group of substances. It is a prodrug of 5-fluorouracil and mainly used to treat solid tumors, such as colorectal, breast and aerodigestive cancers. Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) is the rate-limiting enzyme for fluoropyrimidine metabolism and is therefore responsible for the detoxification of these types of drugs. Patients who are homozygous for variants in DPYD that lead to a non-functional protein, such as *2A or *13, have a high risk of severe or fatal drug toxicities and may benefit from receiving an alternative chemotherapeutic drug. Patients heterozygous for these variants also have an increased risk for drug toxicities, and reduced dosing is recommended for these individuals. Guidelines regarding the use of pharmacogenomic tests in dosing for tegafur have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website. [from PharmGKB]

Professional guidelines

PubMed

Wörmann B, Bokemeyer C, Burmeister T, Köhne CH, Schwab M, Arnold D, Blohmer JU, Borner M, Brucker S, Cascorbi I, Decker T, de Wit M, Dietz A, Einsele H, Eisterer W, Folprecht G, Hilbe W, Hoffmann J, Knauf W, Kunzmann V, Largiadèr CR, Lorenzen S, Lüftner D, Moehler M, Nöthen MM, Pox C, Reinacher-Schick A, Scharl A, Schlegelberger B, Seufferlein T, Sinn M, Stroth M, Tamm I, Trümper L, Wilhelm M, Wöll E, Hofheinz RD
Oncol Res Treat 2020;43(11):628-636. Epub 2020 Oct 23 doi: 10.1159/000510258. PMID: 33099551
Liu GF, Li GJ, Zhao H
J Cell Biochem 2018 Jan;119(1):511-523. Epub 2017 Jul 17 doi: 10.1002/jcb.26210. PMID: 28608558
Deboever G, Hiltrop N, Cool M, Lambrecht G
Clin Colorectal Cancer 2013 Mar;12(1):8-14. Epub 2012 Oct 26 doi: 10.1016/j.clcc.2012.09.003. PMID: 23102544

Recent clinical studies

Etiology

Qiu ZY, Qin R, Tian GY, Zhang Z, Chen M, He H, Xi Y, Wang Y
Medicine (Baltimore) 2021 Apr 30;100(17):e25630. doi: 10.1097/MD.0000000000025630. PMID: 33907117Free PMC Article
Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, Ozaka M, Okano N, Sugimori K, Fukutomi A, Hara H, Mizuno N, Yanagimoto H, Wada K, Tobimatsu K, Yane K, Nakamori S, Yamaguchi H, Asagi A, Yukisawa S, Kojima Y, Kawabe K, Kawamoto Y, Sugimoto R, Iwai T, Nakamura K, Miyakawa H, Yamashita T, Hosokawa A, Ioka T, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J; members of the Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG-HBPOG)
Ann Oncol 2019 Dec 1;30(12):1950-1958. doi: 10.1093/annonc/mdz402. PMID: 31566666
Yonemura Y, Canbay E, Li Y, Coccolini F, Glehen O, Sugarbaker PH, Morris D, Moran B, Gonzaletz-Moreno S, Deraco M, Piso P, Elias D, Batlett D, Ishibashi H, Mizumoto A, Verwaal V, Mahtem H
Eur J Surg Oncol 2016 Aug;42(8):1123-31. Epub 2016 Apr 9 doi: 10.1016/j.ejso.2016.03.016. PMID: 27160355
Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M
Lancet Oncol 2008 Mar;9(3):215-21. Epub 2008 Feb 20 doi: 10.1016/S1470-2045(08)70035-4. PMID: 18282805
Wellington K, Goa KL
Drugs Aging 2001;18(12):935-48; discussion 949-50. doi: 10.2165/00002512-200118120-00005. PMID: 11888348

Diagnosis

Deng GC, Lv Y, Yan H, Sun DC, Qu TT, Pan YT, Han QL, Dai GH
BMC Cancer 2021 Nov 15;21(1):1227. doi: 10.1186/s12885-021-08943-w. PMID: 34781928Free PMC Article
Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J
J Clin Oncol 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10 doi: 10.1200/JCO.2018.77.8613. PMID: 29746229
Abdel-Rahman O, Elsayed Z, Elhalawani H
Cochrane Database Syst Rev 2018 Apr 6;4(4):CD011746. doi: 10.1002/14651858.CD011746.pub2. PMID: 29624208Free PMC Article
Blum M, Suzuki A, Ajani JA
Future Oncol 2011 Jun;7(6):715-26. doi: 10.2217/fon.11.50. PMID: 21675835
Goyle S, Maraveyas A
Dig Surg 2005;22(6):401-14. Epub 2006 Feb 9 doi: 10.1159/000091441. PMID: 16479107

Therapy

Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, Ozaka M, Okano N, Sugimori K, Fukutomi A, Hara H, Mizuno N, Yanagimoto H, Wada K, Tobimatsu K, Yane K, Nakamori S, Yamaguchi H, Asagi A, Yukisawa S, Kojima Y, Kawabe K, Kawamoto Y, Sugimoto R, Iwai T, Nakamura K, Miyakawa H, Yamashita T, Hosokawa A, Ioka T, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J; members of the Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG-HBPOG)
Ann Oncol 2019 Dec 1;30(12):1950-1958. doi: 10.1093/annonc/mdz402. PMID: 31566666
Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J
J Clin Oncol 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10 doi: 10.1200/JCO.2018.77.8613. PMID: 29746229
Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M
Lancet Oncol 2008 Mar;9(3):215-21. Epub 2008 Feb 20 doi: 10.1016/S1470-2045(08)70035-4. PMID: 18282805
Wellington K, Goa KL
Drugs Aging 2001;18(12):935-48; discussion 949-50. doi: 10.2165/00002512-200118120-00005. PMID: 11888348
Kubota Y, Noguchi S, Hosaka M
Oncology (Williston Park) 1999 Jul;13(7 Suppl 3):112-5. PMID: 10442377

Prognosis

Boku N, Ryu MH, Kato K, Chung HC, Minashi K, Lee KW, Cho H, Kang WK, Komatsu Y, Tsuda M, Yamaguchi K, Hara H, Fumita S, Azuma M, Chen LT, Kang YK
Ann Oncol 2019 Feb 1;30(2):250-258. doi: 10.1093/annonc/mdy540. PMID: 30566590Free PMC Article
Zhang H, Shen G, Zhang S, Du F, Cao Y, Jiang J, Zheng F, Ma X, Wang Z, Ren D, Ahmad R, Zhao F, Zhao J
Expert Opin Pharmacother 2018 Jun;19(8):795-807. Epub 2018 Apr 25 doi: 10.1080/14656566.2018.1465928. PMID: 29693454
Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M
Lancet Oncol 2008 Mar;9(3):215-21. Epub 2008 Feb 20 doi: 10.1016/S1470-2045(08)70035-4. PMID: 18282805
Rivera F, Vega-Villegas ME, López-Brea MF
Cancer Treat Rev 2007 Jun;33(4):315-24. Epub 2007 Mar 21 doi: 10.1016/j.ctrv.2007.01.004. PMID: 17376598
Goyle S, Maraveyas A
Dig Surg 2005;22(6):401-14. Epub 2006 Feb 9 doi: 10.1159/000091441. PMID: 16479107

Clinical prediction guides

Morizane C, Okusaka T, Mizusawa J, Katayama H, Ueno M, Ikeda M, Ozaka M, Okano N, Sugimori K, Fukutomi A, Hara H, Mizuno N, Yanagimoto H, Wada K, Tobimatsu K, Yane K, Nakamori S, Yamaguchi H, Asagi A, Yukisawa S, Kojima Y, Kawabe K, Kawamoto Y, Sugimoto R, Iwai T, Nakamura K, Miyakawa H, Yamashita T, Hosokawa A, Ioka T, Kato N, Shioji K, Shimizu K, Nakagohri T, Kamata K, Ishii H, Furuse J; members of the Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG-HBPOG)
Ann Oncol 2019 Dec 1;30(12):1950-1958. doi: 10.1093/annonc/mdz402. PMID: 31566666
Zhang H, Shen G, Zhang S, Du F, Cao Y, Jiang J, Zheng F, Ma X, Wang Z, Ren D, Ahmad R, Zhao F, Zhao J
Expert Opin Pharmacother 2018 Jun;19(8):795-807. Epub 2018 Apr 25 doi: 10.1080/14656566.2018.1465928. PMID: 29693454
Blum M, Suzuki A, Ajani JA
Future Oncol 2011 Jun;7(6):715-26. doi: 10.2217/fon.11.50. PMID: 21675835
Rivera F, Vega-Villegas ME, López-Brea MF
Cancer Treat Rev 2007 Jun;33(4):315-24. Epub 2007 Mar 21 doi: 10.1016/j.ctrv.2007.01.004. PMID: 17376598
Diasio RB
Oncology (Williston Park) 2000 Oct;14(10 Suppl 9):19-23. PMID: 11098485

Recent systematic reviews

Chionh F, Lau D, Yeung Y, Price T, Tebbutt N
Cochrane Database Syst Rev 2017 Jul 28;7(7):CD008398. doi: 10.1002/14651858.CD008398.pub2. PMID: 28752564Free PMC Article
Ter Veer E, Mohammad NH, Lodder P, Ngai LL, Samaan M, van Oijen MG, van Laarhoven HW
Gastric Cancer 2016 Jul;19(3):696-712. Epub 2016 Jan 11 doi: 10.1007/s10120-015-0587-8. PMID: 26754295Free PMC Article
Li D, Chen C, Zhou Y, Chen R, Fan X, Bi Z, Li Z, Liu Y
Medicine (Baltimore) 2015 Sep;94(35):e1345. doi: 10.1097/MD.0000000000001345. PMID: 26334891Free PMC Article
Mehta MP, Paleologos NA, Mikkelsen T, Robinson PD, Ammirati M, Andrews DW, Asher AL, Burri SH, Cobbs CS, Gaspar LE, Kondziolka D, Linskey ME, Loeffler JS, McDermott M, Olson JJ, Patchell RA, Ryken TC, Kalkanis SN
J Neurooncol 2010 Jan;96(1):71-83. Epub 2009 Dec 4 doi: 10.1007/s11060-009-0062-7. PMID: 19960229Free PMC Article
Ward S, Kaltenthaler E, Cowan J, Brewer N
Health Technol Assess 2003;7(32):1-93. doi: 10.3310/hta7320. PMID: 14604497

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