ABSTRACT
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.Subject(s)
Antineoplastic Agents/adverse effects
, Antineoplastic Agents/pharmacokinetics
, Neutropenia/genetics
, Pharmacogenomic Variants
, Polymorphism, Single Nucleotide
, Taxoids/adverse effects
, Taxoids/pharmacokinetics
, Adolescent
, Adult
, Aged
, Aged, 80 and over
, Antineoplastic Agents/administration & dosage
, Databases, Genetic
, Docetaxel
, Female
, Genetic Predisposition to Disease
, Humans
, Inactivation, Metabolic/genetics
, Male
, Membrane Transport Proteins/genetics
, Membrane Transport Proteins/metabolism
, Metabolic Clearance Rate/genetics
, Middle Aged
, Models, Genetic
, Neutropenia/chemically induced
, Pharmacogenetics
, Phenotype
, Risk Factors
, Severity of Illness Index
, Taxoids/administration & dosage
, Young Adult