NADPH 醌氧化还原酶 1 的 C609T 多态性与氨柔比星治疗的肺癌患者临床血液学毒性相关。
C609T Polymorphism of NADPH Quinone Oxidoreductase 1 Correlates Clinical Hematological Toxicities in Lung Cancer Patients Treated with Amrubicin.
机构信息
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University.
出版信息
Clin Med Insights Oncol. 2013;7:31-9. doi: 10.4137/CMO.S10839. Epub 2013 Feb 13.
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.
背景
盐酸氨柔比星（AMR）是治疗肺癌的重要药物。烟酰胺腺嘌呤二核苷酸磷酸醌氧化还原酶 1（NQO1）代谢 AMR 和 AMR-OH 中含有的醌结构。我们假设 NQO1 C609T 多态性可能会影响 AMR 相关药代动力学和临床结局。
方法
患者接受 AMR 剂量为 30 或 40mg/m(2)/天，第 1 天和第 3 天。首次和第三次 AMR 注射后 24 小时进行血浆取样。采用 HPLC 测定 AMR 和 AMR-OH 的浓度，采用 RT-PCR 测定 NQO1 C609T 多态性。
结果
共纳入 35 例患者。在 40mg/m(2)剂量下，T/T 基因型在第 2 天和第 4 天表现出 AMR-OH 浓度降低的趋势。该基因型还表现出显著降低的血液学毒性（P < 0.05）。
结论
NQO1 C609T 多态性与 AMR-OH 的血浆浓度有一定的相关性，从而与血液学毒性有显著的相关性。
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