title: Prospective evaluation of the drug-metabolizing enzyme polymorphisms and toxicity profile of docetaxel in Korean patients with operable lymph node-positive breast cancer receiving adjuvant chemotherapy.
abstract: BACKGROUND
  Inter-individual variability of pharmacokinetics may account for unpredictable toxicities of docetaxel.
  
  
  METHODS
  From March 2007 to June 2008, female patients with operable lymph node-positive breast cancer receiving docetaxel-containing adjuvant chemotherapy were included in this study. The 4 cycles of planned dose of docetaxel (100 mg/m(2)) was performed as adjuvant chemotherapy, following 4 cycles of adriamycin and cyclophosphamide. We evaluated toxicity profile of docetaxel and single nucleotide polymorphisms (SNPs) of CYP3A5 gene, ABCB1 gene, ABCC2 gene and SCLO1B3 gene. Toxicities during treatment of docetaxel were evaluated and defined according to the NCI CTCAE version 3.0.
  
  
  RESULTS
  Pharmacogenetic analysis was performed in 218 Korean women who had received the uniformly planned chemotherapy. With regard to ABCB1 3435 C>T, ABCB1 3435 T/T had significantly higher risks of neutropenia (P = 0.015). Meanwhile, allele frequencies for CYP3A5 6986 G and ABCB1 3435 T revealed a trend for neutropenia (P = 0.107 and 0.068). We could not find any other association between genotypes and other toxicities.
  
  
  CONCLUSIONS
  Although ABCB1 3435 T/T was significantly associated with docetaxel-related neutropenia in our study population, polymorphism of pharmacogenetic genes related to docetaxel metabolism did not appear to be evidently associated with docetaxel-related adverse events.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Poongnap-dong, Songpa-gu, Seoul 138-736, Korea.
authors.forename: Kyu-pyo
authors.initials: KP
authors.lastname: Kim
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Ahn
authors.forename: Sung-Bae
authors.initials: SB
authors.lastname: Kim
authors.forename: Kyung Hae
authors.initials: KH
authors.lastname: Jung
authors.forename: Dok Hyun
authors.initials: DH
authors.lastname: Yoon
authors.forename: Jung Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Sei-Hyun
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant / Q000379:methods; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009503:Neutropenia / Q000139:chemically induced* / Q000453:epidemiology; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D056910:Republic of Korea; D012189:Retrospective Studies; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003520:Cyclophosphamide; D051544:Cytochrome P-450 CYP3A; D000077143:Docetaxel; D004317:Doxorubicin; 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; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C421209:SLCO1B3 protein, human; C510164:CYP3A5 protein, human