%0 Journal Article
%T C609T Polymorphism of NADPH Quinone Oxidoreductase 1 Correlates Clinical Hematological Toxicities in Lung Cancer Patients Treated with Amrubicin
%A Misato Nagata
%A Tatsuo Kimura
%A Tomohiro Suzumura
%A Yukimi Kira
%A Toshiyuki Nakai
%A Kanako Umekawa
%A Hidenori Tanaka
%A Kuniomi Matsuura
%A Shigeki Mitsuoka
%A Naruo Yoshimura
%A Takako Oka
%A Shinzoh Kudoh and Kazuto Hirata
%J Clinical Medicine Insights: Oncology
%D 2012
%I 
%R 10.4137/CMO.S10839
%X 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/m2/day on days 1¨C3. 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/m2, 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.
%U http://www.la-press.com/c609t-polymorphism-of-nadph-quinone-oxidoreductase-1-correlates-clinic-article-a3535