C609T Polymorphism of NADPH Quinone Oxidoreductase 1 Correlates Clinical Hematological Toxicities in Lung Cancer Patients Treated with Amrubicin
C609T Polymorphism of NADPH Quinone Oxidoreductase 1 Correlates Clinical Hematological Toxicities in Lung Cancer Patients Treated with Amrubicin
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DOI：
10.4137/cmo.s10839
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发表时间：
2013-01-01
影响因子：
2.2
通讯作者：
Hirata, Kazuto
中科院分区：
文献类型：
--
作者：
Nagata, Misato;Kimura, Tatsuo;Hirata, Kazuto
背景：盐酸氨柔比星（AMR）是治疗肺癌的一种关键药物。NADPH醌氧化还原酶1（NQO1）可代谢氨柔比星（AMR）和氨柔比星醇（AMR - OH）所含的醌结构。我们假设NQO1 C609T多态性可能影响与AMR相关的药代动力学和临床结果。
方法：患者在第1 - 3天接受剂量为30或40 mg/m²/天的AMR。在首次和第三次注射AMR后24小时采集血浆样本。通过高效液相色谱法（HPLC）测定AMR和AMR - OH的浓度，并通过逆转录聚合酶链反应（RT - PCR）检测NQO1 C609T多态性。
结果：共纳入35例患者。在40 mg/m²剂量下，T/T基因型在第2天和第4天呈现出与AMR - OH浓度降低相关的趋势。该基因型还显示出血液学毒性显著降低（P < 0.05）。
结论：NQO1 C609T多态性与AMR - OH的血浆浓度有相关趋势，因此与血液学毒性有显著相关性。
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.