Details

Autor(en) / Beteiligte

• Nieuweboer, Annemieke JM
• Smid, Marcel
• de Graan, Anne-Joy M
• Elbouazzaoui, Samira
• Bruijn, Peter de
• Martens, John W
• Mathijssen, Ron HJ
• van Schaik, Ron HN

Titel

Predicting paclitaxel-induced neutropenia using the DMET platform

Ist Teil von

• Pharmacogenomics, 2015-07, Vol.16 (11), p.1231-1241

Ort / Verlag

England: Future Medicine Ltd

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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