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 201.

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Keywords DMET™ platform, drug-metabolizing enzymes and transporters, genetic variation, leukopenia, neutropenia, paclitaxel, polymorphisms
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Journal Pharmacogenomics
Nieuweboer, A.J.M, Smid, M, de Graan, A.J.M, Elbouazzaoui, S, de Bruijn, P, Martens, J.W.M, … van Schaik, R.H.N. (2015). Predicting paclitaxel-induced neutropenia using the DMET platform. Pharmacogenomics, 16(11), 1231–1241. doi:10.2217/pgs.15.68