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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
Satoh T, Sakata Y
Expert Opin Pharmacother 2012 Sep;13(13):1943-59. Epub 2012 Aug 4 doi: 10.1517/14656566.2012.709234. PMID: 22860709
van Schaik RH
Invest New Drugs 2005 Dec;23(6):513-22. doi: 10.1007/s10637-005-4019-1. PMID: 16267627

Recent clinical studies

Etiology

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
Zhong S, Qie S, Yang L, Yan Q, Ge L, Wang Z
Medicine (Baltimore) 2017 Jul;96(30):e7611. doi: 10.1097/MD.0000000000007611. PMID: 28746215Free PMC Article
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
Wellington K, Goa KL
Drugs Aging 2001;18(12):935-48; discussion 949-50. doi: 10.2165/00002512-200118120-00005. PMID: 11888348
Langer CJ
Drugs 1999;58 Suppl 3:71-5. doi: 10.2165/00003495-199958003-00010. PMID: 10711844

Diagnosis

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
Zhong S, Qie S, Yang L, Yan Q, Ge L, Wang Z
Medicine (Baltimore) 2017 Jul;96(30):e7611. doi: 10.1097/MD.0000000000007611. PMID: 28746215Free 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
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
Taguchi T
Oncology (Williston Park) 1997 Sep;11(9 Suppl 10):30-4. PMID: 9348564

Prognosis

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
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
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

Zhang X, Liang H, Li Z, Xue Y, Wang Y, Zhou Z, Yu J, Bu Z, Chen L, Du Y, Wang X, Wu A, Li G, Su X, Xiao G, Cui M, Wu D, Chen L, Wu X, Zhou Y, Zhang L, Dang C, He Y, Zhang Z, Sun Y, Li Y, Chen H, Bai Y, Qi C, Yu P, Zhu G, Suo J, Jia B, Li L, Huang C, Li F, Ye Y, Xu H, Wang X, Yuan Y, E JY, Ying X, Yao C, Shen L, Ji J; RESOLVE study group
Lancet Oncol 2021 Aug;22(8):1081-1092. Epub 2021 Jul 9 doi: 10.1016/S1470-2045(21)00297-7. PMID: 34252374
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
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

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
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
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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