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.
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.
Authors: Marie-Rose B S Crombag; Stijn L W Koolen; Sophie Wijngaard; Markus Joerger; Thomas P C Dorlo; Nielka P van Erp; Ron H J Mathijssen; Jos H Beijnen; Alwin D R Huitema Journal: Pharm Res Date: 2019-10-15 Impact factor: 4.200
Authors: Tristan M Sissung; Phoebe A Huang; Ralph J Hauke; Edel M McCrea; Cody J Peer; Roberto H Barbier; Jonathan D Strope; Ariel M Ley; Mary Zhang; Julie A Hong; David Venzon; Jonathan P Jackson; Kenneth R Brouwer; Patrick Grohar; Jon Glod; Brigitte C Widemann; Theo Heller; David S Schrump; William D Figg Journal: Mol Pharmacol Date: 2019-06-07 Impact factor: 4.436
Authors: Mariamena Arbitrio; Maria Teresa Di Martino; Francesca Scionti; Giuseppe Agapito; Pietro Hiram Guzzi; Mario Cannataro; Pierfrancesco Tassone; Pierosandro Tagliaferri Journal: Oncotarget Date: 2016-08-16
Authors: Tristan M Sissung; Arun Rajan; Gideon M Blumenthal; David J Liewehr; Seth M Steinberg; Arlene Berman; Giuseppe Giaccone; William D Figg Journal: PLoS One Date: 2019-02-28 Impact factor: 3.240