ArticleInternational journal of clinical oncology2014
Association between severe toxicity of nilotinib and UGT1A1 polymorphisms in Japanese patients with chronic myelogenous leukemia.
Article in International journal of clinical oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
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- Severe pleural effusion associated with nilotinib for chronic myeloid leukaemia: cross-intolerance with tyrosine kinase inhibitors.BMJ case reports · 2021Article
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- Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies.Frontiers in cardiovascular medicine · 2021Review
- Nilotinib-induced liver injury: A case report.Medicine · 2020Article
- Significance ofJournal of medical biochemistry · 2019Article
- Pharmacogenetics and Pharmacogenomics of Targeted Therapeutics in Chronic Myeloid Leukemia.Molecular diagnosis & therapy · 2017Review
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- Personalized medicine and the clinical laboratory.Einstein (Sao Paulo, Brazil) · 2014Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNilotinib is a BCR-ABL kinase inhibitor approved for the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia (CML). The UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphism UGT1A1*28 (*28)/*28 has been linked to an increased risk of hyperbilirubinemia in patients with CML who receive nilotinib. Beside *28, UGT1A1*6 (*6) is another important variant allele in Japanese patients because it is associated with adverse events of irinotecan, metabolized by UGT1A1. We retrospectively investigated the association between severe toxicity of nilotinib and UGT1A1 polymorphisms (*6 and*28) in Japanese patients with CML. PATIENTS AND
methodsEight patients with cytogenetically confirmed CML who were receiving nilotinib were studied to explore the association of UGT1A1 polymorphisms with severe nilotinib-related toxicity. Genotyping analyses were determined for *6 and *28.
resultsAll 3 patients with the *6/*6 or *6/*28 genotype had severe toxicity, including QT interval prolongation (grade 3), elevated lipase levels (grade 3) plus hyperbilirubinemia (grade 2), and anemia (grade 3) plus hepatic cyst hemorrhage (grade 2) in 1 patient each. Among the 5 patients with the *6/*1 or *1/*1 genotype, 1 had elevated lipase levels (grade 3) and another had severe pain in the lower extremities (grade 3).
conclusionThese findings suggest that UGT1A1 polymorphisms are important determinants of severe toxicity of nilotinib in Japanese patients.
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