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Pharmacogenomics. 2015;16(11):1231-41. doi: 10.2217/pgs.15.68. Epub 2015 Aug 12.

Predicting paclitaxel-induced neutropenia using the DMET platform.

Author information

1
Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
2
Department of Clinical Chemistry, Erasmus University Medical Center, s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.

Abstract

AIM:

The use of paclitaxel in cancer treatment is limited by paclitaxel-induced neutropenia. We investigated the ability of genetic variation in drug-metabolizing enzymes and transporters to predict hematological toxicity.

PATIENTS & METHODS:

Using a discovery and validation approach, we identified a pharmacogenetic predictive model for neutropenia. For this, a drug-metabolizing enzymes and transporters plus DNA chip was used, which contains 1936 SNPs in 225 metabolic enzyme and drug-transporter genes.

RESULTS:

Our 10-SNP model in 279 paclitaxel-dosed patients reached 43% sensitivity in the validation cohort. Analysis in 3-weekly treated patients only resulted in improved sensitivity of 79%, with a specificity of 33%. None of our models reached statistical significance.

CONCLUSION:

Our drug-metabolizing enzymes and transporters-based SNP-models are currently of limited value for predicting paclitaxel-induced neutropenia in clinical practice. Original submitted 9 March 2015; Revision submitted 20 May 2015.

KEYWORDS:

DMETâ„¢ platform; drug-metabolizing enzymes and transporters; genetic variation; leukopenia; neutropenia; paclitaxel; polymorphisms

PMID:
26265135
DOI:
10.2217/pgs.15.68
[Indexed for MEDLINE]

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