Irinotecan and uridine diphosphate glucuronosyltransferase 1A1 pharmacogenetics: to test or not to test, that is the question

Cancer
John F DeekenJohn L Marshall

Abstract

Pharmacogenetic research indicates a relationship between a polymorphism in the gene encoding uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and irinotecan inactivation, in that degradation of SN-38, the active metabolite of irinotecan, correlates inversely with the number of TA repeats in the TATA element of the UGT1A1 promoter region. Individuals who are homozygous for the UGT1A1*28 allele (7 repeats) may exhibit reduced degradation of SN-38 and increased probability of severe toxicities. Clinical study results, as reported in the literature, have not been uniform, however, in showing a relation between genotype and the development of toxicities. Even when correlations are statistically significant, confidence intervals are wide, rendering assessment of individual risk difficult at best. Irinotecan labeling recommends testing for the UGT1A1*28 allele and reducing irinotecan dosing in patients who are positive to reduce the likelihood of dose-limiting neutropenia only, but not diarrhea. Importantly, both dose-limiting neutropenia and diarrhea are dependent on numerous known and unknown factors, such as the specific regimen used, duration of therapy, doses, cycle of treatment, and complexities of irinotecan pharmacody...Continue Reading

References

Nov 2, 1995·The New England Journal of Medicine·P J BosmaR P Oude Elferink
Sep 1, 1996·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H Gurney
May 9, 2001·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J SugataniT Sueyoshi
May 7, 2002·The Pharmacogenomics Journal·L IyerM J Ratain
Aug 16, 2002·Molecular Pharmacology·Robert H TukeyPeter I Mackenzie
Dec 5, 2002·Pharmacogenetics·Federico InnocentiAnna Di Rienzo
Oct 7, 2003·Oncogene·Apurva A DesaiMark J Ratain
Mar 10, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Federico InnocentiMark J Ratain
Mar 11, 2004·Mayo Clinic Proceedings·Matthew P GoetzRichard M Weinshilboum
Jun 5, 2004·Clinical Pharmacology and Therapeutics·Federico Innocenti, Mark J Ratain
Aug 3, 2004·Journal of Clinical Pharmacology·Luca PaoluzziAlex Sparreboom
Aug 7, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elisabeth RouitsErick Gamelin
Oct 8, 2004·Pharmacogenomics·Sharon Marsh, Howard L McLeod
Nov 4, 2004·Journal of the National Cancer Institute·Ron H J MathijssenAlex Sparreboom
Apr 2, 2005·British Journal of Clinical Pharmacology·Qingyu ZhouBalram Chowbay
Apr 15, 2005·Mutation Research·Thierry DervieuxBruce Neri
Nov 1, 2005·Drug Metabolism Reviews·Yuichi Ando, Yoshinori Hasegawa
Nov 8, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Nicola F SmithAlex Sparreboom
Dec 14, 2005·Cancer Letters·Floris A de JongRon H J Mathijssen
Jan 18, 2006·Annual Review of Medicine·Michel EichelbaumWilliam E Evans
Apr 26, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Federico InnocentiMark J Ratain
Jul 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Giuseppe ToffoliSergio Frustaci
Sep 30, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Peter J O'Dwyer, Robert B Catalano
Nov 9, 2006·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Kristine K HahnJill M Kolesar
Dec 14, 2006·Advances in Experimental Medicine and Biology·Heinz-Josef Lenz
Dec 23, 2006·Pharmacogenomics·Federico Innocenti, Mark J Ratain
Dec 29, 2006·Journal of Clinical Pharmacology·Roshni P RamchandaniJogarao V S Gobburu
May 19, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jean-François CôtéMarc Ychou
Aug 31, 2007·Journal of the National Cancer Institute·Janelle M HoskinsHoward L McLeod

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Citations

Dec 3, 2008·Expert Opinion on Emerging Drugs·David R FogelmanCathy Eng
Aug 30, 2012·British Journal of Cancer·E ChatelutA Sparreboom
Jul 1, 2009·Personalized Medicine·Elizabeth J Phillips, Simon A Mallal
Aug 11, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Steven G DuBoisAraz Marachelian
Mar 17, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Steven G DuBoisKatherine K Matthay

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