title: C609T Polymorphism of NADPH Quinone Oxidoreductase 1 Correlates Clinical Hematological Toxicities in Lung Cancer Patients Treated with Amrubicin.
abstract: BACKGROUND
  Amrubicin hydrochloride (AMR) is a key agent for lung cancer. NADPH quinone oxidoreductase 1 (NQO1) metabolizes the quinone structures contained in both amrubicin (AMR) and amrubicinol (AMR-OH). We hypothesized that NQO1 C609T polymorphism may affect AMR-related pharmacokinetics and clinical outcomes.
  
  
  METHODS
  Patients received AMR doses of 30 or 40 mg/m(2)/day on days 1-3. Plasma sampling was performed 24 hours after the first and third AMR injections. Concentrations of AMR and AMR-OH were determined by HPLC and the NQO1 C609T polymorphism was assayed by RT-PCR.
  
  
  RESULTS
  A total of 35 patients were enrolled. At a dose of 40 mg/m(2), the T/T genotype exhibited a tendency toward a relationship with decrease concentrations of AMR-OH on days 2 and 4. The genotype also showed a significant decrease of hematological toxicities (P < 0.05).
  
  
  CONCLUSIONS
  NQO1 C609T polymorphism had a tendency of correlation with the plasma concentrations of AMR-OH, and thereby had significant correlations with hematologic toxicities.
authors: Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University.
authors: Misato
authors: M
authors: Nagata
authors: Tatsuo
authors: T
authors: Kimura
authors: Tomohiro
authors: T
authors: Suzumura
authors: Yukimi
authors: Y
authors: Kira
authors: Toshiyuki
authors: T
authors: Nakai
authors: Kanako
authors: K
authors: Umekawa
authors: Hidenori
authors: H
authors: Tanaka
authors: Kuniomi
authors: K
authors: Matsuura
authors: Shigeki
authors: S
authors: Mitsuoka
authors: Naruo
authors: N
authors: Yoshimura
authors: Takako
authors: T
authors: Oka
authors: Shinzoh
authors: S
authors: Kudoh
authors: Kazuto
authors: K
authors: Hirata
keywords: NQO1; SNP; amrubicin; hematological toxicity; lung cancer