Clin Cancer Res 2008 Mar;14(6):1788-96
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Download full-text PDF
J Pharmacol Exp Ther 2013 Apr 5;345(1):95-101. Epub 2013 Feb 5.
Pharmacogenomics Laboratory, Centre Hospitalier de l’Université Laval (CHU de Québec) Research Center and Faculty of Pharmacy, Laval University, Quebec, Canada.
Despite the importance of UDP-glucuronosyltransferase (UGT) 1A1*28 in irinotecan pharmacogenetics, our capability to predict drug-induced severe toxicity remains limited. We aimed at identifying novel genetic markers that would improve prediction of irinotecan toxicity and response in advanced colorectal cancer patients treated with folic acid (leucovorin), fluorouracil (5-FU), and irinotecan (camptosar)-based regimens. The relationships between UGT1A candidate markers across the gene (n = 21) and toxicity were prospectively evaluated in 167 patients. Read More
Pharmacogenomics 2009 Jul;10(7):1139-46
UNC Institute for Pharmacogenomics & Individualized Therapy, University of North Carolina, Genetic Medicine Building, Chapel Hill, NC 27599-7360, USA.
Aims: A recent study found that variation in camptothecin pharmacodynamic genes (TOP1, PARP1, TDP1 and XRCC1) correlated with efficacy and risk of neutropenia in irinotecan-treated cancer patients (median dose: 180 mg/m2), which suggests that these genes might predict outcomes to irinotecan-based therapies. The present study was conducted to evaluate previous gene associations using an independent sample of patients receiving irinotecan.
Materials & Methods: DNA was isolated from 85 advanced cancer patients treated with 300 or 350 mg/m2 irinotecan and genotyped for haplotype-tag polymorphisms across TOP1, PARP1, TDP1 and XRCC1. Read More
Pharmacogenet Genomics 2007 Jul;17(7):497-504
Division of Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Objectives: SN-38, an active metabolite of irinotecan, is detoxified by glucuronidation with UGT1A isoforms, 1A1, 1A7, 1A9, and 1A10. The pharmacogenetic information on UGT1A haplotypes covering all these isoforms is important for the individualized therapy of irinotecan. Associations between UGT1A haplotypes and pharmacokinetics/pharmacodynamics of irinotecan were investigated to identify pharmacogenetic markers. Read More
Curr Clin Pharmacol 2010 Aug;5(3):209-17
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospotal, Memphis, TN 38105-3678, USA.
Irinotecan (CPT-11) is a widely used anticancer drug, especially for the treatment of colorectal cancer. Irinotecan is considered an inactive prodrug that requires activation to the active metabolite SN-38. Patients treated with irinotecan occasionally experience severe neutropenia and delayed diarrhea, and the occurrence of these adverse reactions is unpredictable and still largely unexplained. Read More