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Fluorouracil response

MedGen UID:
450455
Concept ID:
CN077983
Sign or Symptom
Synonyms: 5-fluorouracil toxicity; 5-fluorouracil toxicity, included; 5-FU
Drug:
Fluorouracil
MedGen UID:
450004
Concept ID:
CN077529
Pharmacologic Substance
 

Definition

5-fluorouracil is a chemotherapeutic agent, and a member of the fluoropyrimidine group of substances. It is 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 5-fluorouracil have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (http://www.pharmgkb.org/drug/PA128406956). [from PharmGKB]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Caudle KE, Thorn CF, Klein TE, Swen JJ, McLeod HL, Diasio RB, Schwab M
Clin Pharmacol Ther 2013 Dec;94(6):640-5. Epub 2013 Aug 29 doi: 10.1038/clpt.2013.172. [Epub ahead of print] PMID: 23988873Free PMC Article

External

DailyMed Drug Label, ADRUCIL, 2012

Recent clinical studies

Etiology

Candy PA, Phillips MR, Redfern AD, Colley SM, Davidson JA, Stuart LM, Wood BA, Zeps N, Leedman PJ
Br J Cancer 2013 Aug 20;109(4):1023-30. Epub 2013 Jul 30 doi: 10.1038/bjc.2013.431. [Epub ahead of print] PMID: 23900217Free PMC Article
Bracht K, Nicholls AM, Liu Y, Bodmer WF
Br J Cancer 2010 Jul 27;103(3):340-6. Epub 2010 Jul 6 doi: 10.1038/sj.bjc.6605780. [Epub ahead of print] PMID: 20606684Free PMC Article
Showalter SL, Showalter TN, Witkiewicz A, Havens R, Kennedy EP, Hucl T, Kern SE, Yeo CJ, Brody JR
Cancer Biol Ther 2008 Jul;7(7):986-94. Epub 2008 Apr 21 [Epub ahead of print] PMID: 18443433Free PMC Article
Gusella M, Padrini R
Pharmacogenomics 2007 Aug;8(8):985-96. doi: 10.2217/14622416.8.8.985. PMID: 17716232
Payne JE, Pheils MT, Chapuis PH, MacPherson JG
Aust N Z J Surg 1981 Feb;51(1):12-6. PMID: 7013747

Diagnosis

Funkhouser WK Jr, Lubin IM, Monzon FA, Zehnbauer BA, Evans JP, Ogino S, Nowak JA
J Mol Diagn 2012 Mar-Apr;14(2):91-103. Epub 2012 Jan 17 doi: 10.1016/j.jmoldx.2011.11.001. [Epub ahead of print] PMID: 22260991
Bracht K, Nicholls AM, Liu Y, Bodmer WF
Br J Cancer 2010 Jul 27;103(3):340-6. Epub 2010 Jul 6 doi: 10.1038/sj.bjc.6605780. [Epub ahead of print] PMID: 20606684Free PMC Article
Wong CS, Wong VW, Chan CM, Ma BB, Hui EP, Wong MC, Lam MY, Au TC, Chan WH, Cheuk W, Chan AT
Oncol Rep 2008 Jul;20(1):89-98. PMID: 18575723
Showalter SL, Showalter TN, Witkiewicz A, Havens R, Kennedy EP, Hucl T, Kern SE, Yeo CJ, Brody JR
Cancer Biol Ther 2008 Jul;7(7):986-94. Epub 2008 Apr 21 [Epub ahead of print] PMID: 18443433Free PMC Article
Payne JE, Pheils MT, Chapuis PH, MacPherson JG
Aust N Z J Surg 1981 Feb;51(1):12-6. PMID: 7013747

Therapy

Candy PA, Phillips MR, Redfern AD, Colley SM, Davidson JA, Stuart LM, Wood BA, Zeps N, Leedman PJ
Br J Cancer 2013 Aug 20;109(4):1023-30. Epub 2013 Jul 30 doi: 10.1038/bjc.2013.431. [Epub ahead of print] PMID: 23900217Free PMC Article
Showalter SL, Showalter TN, Witkiewicz A, Havens R, Kennedy EP, Hucl T, Kern SE, Yeo CJ, Brody JR
Cancer Biol Ther 2008 Jul;7(7):986-94. Epub 2008 Apr 21 [Epub ahead of print] PMID: 18443433Free PMC Article
Wu X, Lu C, Chiang SS, Ajani JA
Semin Oncol 2005 Dec;32(6 Suppl 9):S87-9. doi: 10.1053/j.seminoncol.2005.04.031. PMID: 16399440
Payne JE, Pheils MT, Chapuis PH, MacPherson JG
Aust N Z J Surg 1981 Feb;51(1):12-6. PMID: 7013747

Prognosis

Candy PA, Phillips MR, Redfern AD, Colley SM, Davidson JA, Stuart LM, Wood BA, Zeps N, Leedman PJ
Br J Cancer 2013 Aug 20;109(4):1023-30. Epub 2013 Jul 30 doi: 10.1038/bjc.2013.431. [Epub ahead of print] PMID: 23900217Free PMC Article
Funkhouser WK Jr, Lubin IM, Monzon FA, Zehnbauer BA, Evans JP, Ogino S, Nowak JA
J Mol Diagn 2012 Mar-Apr;14(2):91-103. Epub 2012 Jan 17 doi: 10.1016/j.jmoldx.2011.11.001. [Epub ahead of print] PMID: 22260991
Showalter SL, Showalter TN, Witkiewicz A, Havens R, Kennedy EP, Hucl T, Kern SE, Yeo CJ, Brody JR
Cancer Biol Ther 2008 Jul;7(7):986-94. Epub 2008 Apr 21 [Epub ahead of print] PMID: 18443433Free PMC Article
Wu X, Lu C, Chiang SS, Ajani JA
Semin Oncol 2005 Dec;32(6 Suppl 9):S87-9. doi: 10.1053/j.seminoncol.2005.04.031. PMID: 16399440
Payne JE, Pheils MT, Chapuis PH, MacPherson JG
Aust N Z J Surg 1981 Feb;51(1):12-6. PMID: 7013747

Clinical prediction guides

Candy PA, Phillips MR, Redfern AD, Colley SM, Davidson JA, Stuart LM, Wood BA, Zeps N, Leedman PJ
Br J Cancer 2013 Aug 20;109(4):1023-30. Epub 2013 Jul 30 doi: 10.1038/bjc.2013.431. [Epub ahead of print] PMID: 23900217Free PMC Article
Funkhouser WK Jr, Lubin IM, Monzon FA, Zehnbauer BA, Evans JP, Ogino S, Nowak JA
J Mol Diagn 2012 Mar-Apr;14(2):91-103. Epub 2012 Jan 17 doi: 10.1016/j.jmoldx.2011.11.001. [Epub ahead of print] PMID: 22260991
Showalter SL, Showalter TN, Witkiewicz A, Havens R, Kennedy EP, Hucl T, Kern SE, Yeo CJ, Brody JR
Cancer Biol Ther 2008 Jul;7(7):986-94. Epub 2008 Apr 21 [Epub ahead of print] PMID: 18443433Free PMC Article
Wu X, Lu C, Chiang SS, Ajani JA
Semin Oncol 2005 Dec;32(6 Suppl 9):S87-9. doi: 10.1053/j.seminoncol.2005.04.031. PMID: 16399440
Payne JE, Pheils MT, Chapuis PH, MacPherson JG
Aust N Z J Surg 1981 Feb;51(1):12-6. PMID: 7013747

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