The association between the UGT1A1*28 genotype and the severe toxicity of low-dose irinotecan has been controversial, and few studies have examined this association in patients with lung cancer. The aim of this study was to assess the association between the UGT1A1*28 genotype and the severe toxicity of low-dose irinotecan in Japanese patients with lung cancer. From December 2005 through July 2008, 53 Japanese patients with advanced lung cancer who underwent chemotherapy that included low-dose irinotecan (50 or 60 mg/m2) as a single agent or in combination chemotherapy were retrospectively analyzed. Genomic DNA was extracted from peripheral blood. Genotypes for the UGT1A1*28 were denoted as wild-type for 6/6, heterozygous for 6/7, or homozygous for 7/7 depending on the number of TA repeats found in each allele. Of the 53 patients, 42 (79.2%) were wild-type, 9 (17.0%) were heterozygous, and 2 (3.7%) were homozygous for the UGT1A1*28 genotype. The UGT1A1*28 genotype was not associated with grade 3 or 4 neutropenia, thrombocytopia, diarrhea, or febrile neutropenia. The frequency of dose reduction of irinotecan did not differ between wild-type and heterozygous or homozygous for the UGT1A1*28 genotype. In addition, there were no significant differences in response rates and survival between wild-type and heterozygous or homozygous for the UGT1A1*28 genotype. In conclusion, the UGT1A1*28 genotype did not predict the severe toxicity of low-dose irinotecan in patients with lung cancer. Therefore, low-dose irinotecan could be administered without reducing starting dose in patients with UGT1A1*28 genotype.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.3727/096504010x12626118079822 | DOI Listing |
ESMO Open
February 2023
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:
Background: Initial dose adjustment is recommended for patients with known UGT1A1∗28 homozygosity for both conventional irinotecan and liposomal irinotecan (nal-IRI). A recent population pharmacokinetic (PK) study showed that Asian patients had a lower prevalence of UGT1A1∗28 homozygosity but a significantly higher maximum blood concentration of SN-38 (SN-38 Cmax) and a higher incidence of grade ≥3 neutropenia after nal-IRI administration than Caucasian patients. The current study investigated the association of UGT1A1 polymorphisms, including the Asian prevalent UGT1A1∗6, PK and toxicities of nal-IRI-based therapy in the Asian population.
View Article and Find Full Text PDFJ Clin Lab Anal
June 2022
Genomics of Signalopathies at the service of Medicine, Medical University of Sfax, Sfax, Tunisia.
Background: Uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1), which is the major UGT1 gene product, is located on chromosome 2q37. The expression of UGT1A1 is relatively managed by a polymorphic dinucleotide repeat inside the promoter TATA box consisting of 5-8 copies of a TA repeat. A (TA) 6TAA is considered as the wild type.
View Article and Find Full Text PDFEur J Cancer
February 2022
Department of Clinical Pharmacy, Catharina Hospital, Eindhoven, the Netherlands; Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden, the Netherlands. Electronic address:
Aim: To determine the safety, feasibility, pharmacokinetics, and cost of UGT1A1 genotype-guided dosing of irinotecan.
Patients And Methods: In this prospective, multicentre, non-randomised study, patients intended for treatment with irinotecan were pre-therapeutically genotyped for UGT1A1∗28 and UGT1A1∗93. Homozygous variant carriers (UGT1A1 poor metabolisers; PMs) received an initial 30% dose reduction.
J Clin Exp Hepatol
February 2021
Division of Molecular and Radiation Biophysics, National Research Center "Kurchatov Institute" B.P.Konstantinov St Petersburg Nuclear Physics Institute, Gatchina, 188300, Russia.
Background/objectives: Gilbert's syndrome (GS) is a hereditary pathology that affects approximately 10% of the world's population. In most cases, GS is associated with the polymorphism of gene coding the enzyme bilirubin uridine diphosphate glucuronosyltransferase (UGT-1A) which plays a key role in the bilirubin metabolism. The presence of an additional TA repeat in the TATA box of the gene promoter (the allelic variant of 7TA, abbreviated as ) leads to a significant decrease in the enzymatic activity of UGT-1A in the liver and to decrease in glucuronidation process as a consequence.
View Article and Find Full Text PDFEur J Cancer
December 2020
Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address:
Background: Pre-therapeutic UGT1A1 genotyping is not yet routinely performed in most hospitals in patients starting irinotecan chemotherapy. The aim of this position paper was to evaluate the available evidence and to assess the potential value of genotyping of UGT1A1∗28 and UGT1A1*6 in patients before starting treatment with irinotecan to reduce the risk of severe toxicity.
Methods: The literature was selected and assessed based on five pre-specified criteria: 1) the level of evidence for associations between UGT1A1 polymorphisms and irinotecan-induced severe toxicity, 2) clinical validity and utility of pre-therapeutic genotyping of UGT1A1, 3) safety and tolerability of irinotecan in carriers of UGT1A1 polymorphisms, 4) availability of specific dose recommendations for irinotecan in carriers of UGT1A1 polymorphisms, 5) evidence of cost benefits of pre-therapeutic genotyping of UGT1A1.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!