Predicting paclitaxel-induced neutropenia using the DMET platform

Pharmacogenomics. 2015;16(11):1231-41. doi: 10.2217/pgs.15.68. Epub 2015 Aug 12.


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.

Keywords: DMETâ„¢ platform; drug-metabolizing enzymes and transporters; genetic variation; leukopenia; neutropenia; paclitaxel; polymorphisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Neutropenia / chemically induced*
  • Neutropenia / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Paclitaxel / adverse effects*
  • Polymorphism, Single Nucleotide / genetics
  • Predictive Value of Tests
  • Prospective Studies
  • Sensitivity and Specificity
  • Young Adult


  • Antineoplastic Agents, Phytogenic
  • Membrane Transport Proteins
  • Paclitaxel