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Clinical validity of new genetic biomarkers of irinotecan neutropenia: an independent replication study
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Clinical validity of new genetic biomarkers of irinotecan neutropenia: an independent replication study
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Journal Article
Clinical validity of new genetic biomarkers of irinotecan neutropenia: an independent replication study
2016
Overview
The overall goal of this study was to provide evidence for the clinical validity of nine genetic variants in five genes previously associated with irinotecan neutropenia and pharmacokinetics. Variants associated with absolute neutrophil count (ANC) nadir and/or irinotecan pharmacokinetics in a discovery cohort of cancer patients were genotyped in an independent replication cohort of 108 cancer patients. Patients received single-agent irinotecan every 3 weeks. For ANC nadir, we replicated
UGT1A1*28
,
UGT1A1*93
and
SLCO1B1*1b
in univariate analyses. For irinotecan area under the concentration–time curve (AUC
0-24
), we replicated
ABCC2 -24C>T
; however,
ABCC2 -24C>T
only predicted a small fraction of the variance. For SN-38 AUC
0-24
and the glucuronidation ratio, we replicated
UGT1A1*28
and
UGT1A1*93.
In addition to
UGT1A1*28
, this study independently validated
UGT1A1*93
and
SLCO1B1*1b
as new predictors of irinotecan neutropenia. Further demonstration of their clinical utility will optimize irinotecan therapy in cancer patients.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adult
/ Aged
/ Antineoplastic Agents - adverse effects
/ Antineoplastic Agents - pharmacokinetics
/ Biomedical and Life Sciences
/ Camptothecin - adverse effects
/ Camptothecin - analogs & derivatives
/ Camptothecin - pharmacokinetics
/ Cancer
/ Female
/ Genotype
/ Humans
/ Identification and classification
/ Male
/ Neutropenia - chemically induced
/ Oncology
/ Patients
