Role of genetic variation in docetaxel-induced neutropenia and pharmacokinetics

Docetaxel is used for treatment of several solid malignancies. In this study, we aimed for predicting docetaxel clearance and docetaxel-induced neutropenia by developing several genetic models. Therefore, pharmacokinetic data and absolute neutrophil counts (ANCs) of 213 docetaxel-treated cancer patients were collected. Next, patients were genotyped for 1936 single nucleotide polymorphisms (SNPs) in 225 genes using the drug-metabolizing enzymes and transporters platform and thereafter split into two cohorts. The combination of SNPs that best predicted severe neutropenia or low clearance was selected in one cohort and validated in the other. Patients with severe neutropenia had lower docetaxel clearance than patients with ANCs in the normal range (P=0.01). Severe neutropenia was predicted with 70% sensitivity. True low clearance (1 s.d.<mean clearance) was identified in 80% of cases. These models however did not reach statistical significance. To improve the predictive value of these models, the addition of non-genetic influencing factors is needed.The Pharmacogenomics Journal advance online publication, 8 September 2015; doi:10.1038/tpj.2015.66.

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