Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An association between UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) polymorphisms and irinotecan-induced neutropenia has been previously reported. In this study, we assessed the clinical usefulness of testing for UGT1A1 polymorphisms prior to the initiation of irinotecan-based chemotherapy, as this remains a controversial subject. A total of 136 lung cancer patients who were treated with a combination of nedaplatin and irinotecan as initial chemotherapy were assessed. Following exclusion of patients exhibiting low UGT1A1 enzyme activity, 70 patients were treated after UGT1A1 polymorphism testing (test group) and 66 patients were treated without UGT1A1 polymorphism testing (non-test group). We retrospectively analyzed and compared the adverse events between the test and the non-test groups and observed no reduction in hematological or non-hematological toxicities in the test group compared to that in the non-test group. Of the 9 patients with grade 4 or 5 non-hematological toxicity, 6 patients had febrile neutropenia (FN). All the patients with FN were aged >70 years. The incidence of adverse events was significantly higher among patients aged >70 years compared to that among younger patients. In conclusion, in patients treated with nedaplatin and irinotecan combination chemotherapy, UGT1A1 polymorphism testing prior to the initiation of chemotherapy did not reduce the incidence of adverse events. Therefore, UGT1A1 polymorphism testing alone may not be sufficient to predict the occurrence of severe adverse events and it may be more important to effectively manage adverse events, particularly in elderly patients.
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PMID:Clinical usefulness of testing for UDP glucuronosyltransferase 1 family, polypeptide A1 polymorphism prior to the inititation of irinotecan-based chemotherapy. 2505 39

Certain genetic polymorphisms of UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) can reduce gene expression (*28, *60, *93) or activity (*6), thereby altering the pharmacokinetics, pharmacodynamics, and the risk of toxicities of UGT1A1 substrates, of which irinotecan is a widely-described example. This review presents an overview of the clinical effects of UGT1A1 polymorphisms on the pharmacology of UGT1A1 substrates, with a special focus on the novel histone deacetylase inhibitor belinostat. Belinostat, approved for the treatment of peripheral T-cell lymphoma, is primarily glucuronidated by UGT1A1. Recent preclinical and clinical data showed that UGT1A1*28 was associated with reduced glucuronidation in human liver microsomes, while in a retrospective analysis of a Phase I trial with patients receiving belinostat UGT1A1*60 was predominantly associated with increased belinostat plasma concentrations. Furthermore, both UGT1A1*28 and *60 variants were associated with increased incidence of thrombocytopenia and neutropenia. Using population pharmacokinetic analysis a 33% dose reduction has been proposed for patients carrying UGT1A1 variant alleles. Clinical effects of this genotype-based dosing recommendation is currently prospectively being investigated. Overall, the data suggest that UGT1A1 genotyping is useful for improving belinostat therapy.
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PMID:UGT genotyping in belinostat dosing. 2677 2