title: Retrospective analysis of severe neutropenia in patients receiving concomitant administration of docetaxel and clarithromycin.
abstract: BACKGROUND
  Neutropenia is one of the most important dose-limiting toxicities of docetaxel. Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Clarithromycin, a potent inhibitor of CYP3A4, is occasionally used in combination with docetaxel. The aim of this study was to evaluate whether the risk of severe neutropenia induced by docetaxel was increased by concomitant administration of clarithromycin.
  
  
  METHODS
  Patients with advanced lung cancer receiving docetaxel were identified from an electronic medical record system and divided into 2 groups: concomitant administration of clarithromycin and no concomitant administration of clarithromycin. The proportion of patients experiencing grade 4 neutropenia between the 2 groups was compared. Potential risk factors associated with grade 4 neutropenia were also examined using univariate and multivariate logistic regression analyses.
  
  
  RESULTS
  One hundred and fifty-eight patients were analysed. Grade 4 neutropenia was more frequently detected in the patients receiving clarithromycin than in those not receiving the drug (63.2 vs. 35.3%; p = 0.025). Multivariate analysis showed that co-administration of clarithromycin [odds ratio (OR) 4.98; p = 0.004], pre-treatment absolute neutrophil count (OR 2.62; p = 0.011) and female gender (OR 2.75; p = 0.029) resulted in an increase in the incidence of grade 4 neutropenia.
  
  
  CONCLUSIONS
  This study shows that concomitant administration of clarithromycin potentiated docetaxel-induced myelosuppression.
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Tsuji
authors.forename: Mana
authors.initials: M
authors.lastname: Kamezato
authors.forename: Takashi
authors.initials: T
authors.lastname: Daimon
authors.forename: Keisei
authors.initials: K
authors.lastname: Taku
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hatori
authors.forename: Midori
authors.initials: M
authors.lastname: Ikeda
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Inoue
authors.forename: Takashi
authors.initials: T
authors.lastname: Eto
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D017291:Clarithromycin / Q000008:administration & dosage / Q000009:adverse effects*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology*; D016017:Odds Ratio; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012737:Sex Factors; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D017291:Clarithromycin