Cited 12 times since 2015 (1.2 per year) source: EuropePMC Pharmacogenomics, Volume 16, Issue 11, 12 2 2015, Pages 1231-1241 Predicting paclitaxel-induced neutropenia using the DMET platform. Nieuweboer AJ, Smid M, de Graan AJ, Elbouazzaoui S, de Bruijn P, Martens JW, Mathijssen RH, van Schaik RH
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.
