Predicting paclitaxel-induced neutropenia using the DMET platform
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Annemieke J M Nieuweboer1, Marcel Smid1, Anne-Joy M de Graan1
1Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
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.
