C609T polymorphism of NADPH Quinone Oxidoreductase 1 Correlates Clinical Hematological Toxicities in Lung Cancer Patients Treated with Amrubicin. (January 2013)

• Record Type: Journal Article
• Authors: Nagata, Misato; Kimura, Tatsuo; Suzumura, Tomohiro; Kira, Yukimi; Nakai, Toshiyuki; Umekawa, Kanako; Tanaka, Hidenori; Matsuura, Kuniomi; Mitsuoka, Shigeki; Yoshimura, Naruo; Oka, Takako; Kudoh, Shinzoh; Hirata, Kazuto
• Is Part Of: Clinical medicine insights. Oncology. Volume 7(2013)
• Publication Date: 2013-01
• Subjects: NQO1 -- amrubicin -- lung cancer -- SNP -- hematological toxicity; Oncology -- Periodicals; 616.994005
• DOI: 10.4137/CMO.S10839
• Languages: English
• ISSNs: 1179-5549

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 NQO 1 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 NQO 1 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: NQO 1 C609T polymorphism had a tendency of correlation with the plasma concentrations of AMR-OH, and thereby had significant correlations with hematologic toxicities.