title: The relationship of polymorphisms in ABCC2 and SLCO1B3 with docetaxel pharmacokinetics and neutropenia:  CALGB 60805 (Alliance).
abstract: Docetaxel-related neutropenia was associated with polymorphisms in the drug transporters ABCC2 and SLCO1B3 in Japanese cancer patients. We hypothesized that this association is because of reduced docetaxel clearance, associated with polymorphisms in those genes. We studied 64 US cancer patients who received a single cycle of 75 mg/m of docetaxel monotherapy. We found that the ABCC2 polymorphism at rs-12762549 trended to show a relationship with reduced docetaxel clearance (P=0.048), but not with neutropenia. There was no significant association of the SLCO1B3 polymorphisms with docetaxel clearance or neutropenia. We conclude that the relationship between docetaxel-associated neutropenia and polymorphisms in drug transporters identified in Japanese patients was not confirmed in this cohort of US cancer patients.
authors.affiliation: Sections of Clinical Pharmacology and Hematology/Oncology, Department of Medicine, The Geisel School of Medicine at Dartmouth, The Norris Cotton Cancer Center, Lebanon, NH 03756, USA. lionel.d.lewis@dartmouth.edu
authors.forename: Lionel D
authors.initials: LD
authors.lastname: Lewis
authors.forename: Antonius A
authors.initials: AA
authors.lastname: Miller
authors.forename: Kouros
authors.initials: K
authors.lastname: Owzar
authors.forename: Robert R
authors.initials: RR
authors.lastname: Bies
authors.forename: Svetlana
authors.initials: S
authors.lastname: Markova
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Kroetz
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Egorin
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ratain
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D009503:Neutropenia / Q000139:chemically induced / Q000235:genetics*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D043823:Taxoids / Q000009:adverse effects / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D000077143:Docetaxel; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029362:Organic Anion Transporters, Sodium-Independent; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D043823:Taxoids; C000715087:ABCC2 protein, human; C421209:SLCO1B3 protein, human