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UGT1A1 Guided Cancer Therapy: Review of the Evidence and Considerations for Clinical Implementation. [Review]

MedStar author(s):

Citation: Cancers. 13(7), 2021 Mar 29.PMID: 33805415Department: Associate Dean for Research Development | MedStar HealthForm of publication: Journal ArticleMedline article type(s): Journal Article | ReviewSubject headings: IN PROCESS -- NOT YET INDEXEDYear: 2021 ISSN:

2072-6694

Name of journal: CancersAbstract: Multi-gene assays often include UGT1A1 and, in certain instances, may report associated toxicity risks for irinotecan, belinostat, pazopanib, and nilotinib. However, guidance for incorporating UGT1A1 results into therapeutic decision-making is mostly lacking for these anticancer drugs. We summarized meta-analyses, genome-wide association studies, clinical trials, drug labels, and guidelines relating to the impact of UGT1A1 polymorphisms on irinotecan, belinostat, pazopanib, or nilotinib toxicities. For irinotecan, UGT1A1*28 was significantly associated with neutropenia and diarrhea, particularly with doses >= 180 mg/m2, supporting the use of UGT1A1 to guide irinotecan prescribing. The drug label for belinostat recommends a reduced starting dose of 750 mg/m2 for UGT1A1*28 homozygotes, though published studies supporting this recommendation are sparse. There was a correlation between UGT1A1 polymorphisms and pazopanib-induced hepatotoxicity, though further studies are needed to elucidate the role of UGT1A1-guided pazopanib dose adjustments. Limited studies have investigated the association between UGT1A1 polymorphisms and nilotinib-induced hepatotoxicity, with data currently insufficient for UGT1A1-guided nilotinib dose adjustments.All authors: Bottiglieri S, Carballido E, Cueto AD, Hicks JK, Imanirad I, Levine R, Nelson RS, Parker AS, Seligson ND, Swain SM, Tillman EMFiscal year: FY2021Digital Object Identifier:

https://dx.doi.org/10.3390/cancers13071566

Date added to catalog: 2021-06-07

Holdings ( 1 )
Title notes ( 2 )

Holdings
Item type	Current library	Collection	Call number	Status	Date due	Barcode
Journal Article	MedStar Authors Catalog	Article	33805415	Available		33805415

Multi-gene assays often include UGT1A1 and, in certain instances, may report associated toxicity risks for irinotecan, belinostat, pazopanib, and nilotinib. However, guidance for incorporating UGT1A1 results into therapeutic decision-making is mostly lacking for these anticancer drugs. We summarized meta-analyses, genome-wide association studies, clinical trials, drug labels, and guidelines relating to the impact of UGT1A1 polymorphisms on irinotecan, belinostat, pazopanib, or nilotinib toxicities. For irinotecan, UGT1A1*28 was significantly associated with neutropenia and diarrhea, particularly with doses >= 180 mg/m2, supporting the use of UGT1A1 to guide irinotecan prescribing. The drug label for belinostat recommends a reduced starting dose of 750 mg/m2 for UGT1A1*28 homozygotes, though published studies supporting this recommendation are sparse. There was a correlation between UGT1A1 polymorphisms and pazopanib-induced hepatotoxicity, though further studies are needed to elucidate the role of UGT1A1-guided pazopanib dose adjustments. Limited studies have investigated the association between UGT1A1 polymorphisms and nilotinib-induced hepatotoxicity, with data currently insufficient for UGT1A1-guided nilotinib dose adjustments.

English