Clinical usefulness of testing for UDP glucuronosyltransferase 1 family, polypeptide A1 polymorphism prior to the inititation of irinotecan-based chemotherapy
Clinical usefulness of testing for UDP glucuronosyltransferase 1 family, polypeptide A1 polymorphism prior to the inititation of irinotecan-based chemotherapy
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DOI：
10.3892/mco.2014.308
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发表时间：
2014-09-01
影响因子：
1.2
通讯作者：
Yamada, Kouzo
中科院分区：
文献类型：
--
作者：
Harada, Taishi;Saito, Haruhiro;Yamada, Kouzo
先前已报告UDP葡萄糖醛酸基转移酶1家族、多肽A1（UGT1A1）多态性与伊立替康诱导的中性粒细胞减少症之间的关联。在这项研究中，我们评估了在开始基于伊立替康的化疗之前检测UGT1A1多态性的临床有用性，因为这仍然是一个有争议的话题。共评估了136例接受奈达铂和伊立替康联合化疗的肺癌患者。排除UGT1A1酶活性低的患者后，70例患者在UGT1A1多态性检测后接受治疗（试验组），66例患者在未进行UGT1A1多态性检测的情况下接受治疗（非试验组）。我们回顾性分析和比较了试验组和非试验组之间的不良事件，并观察到与非试验组相比，试验组的血液学或非血液学毒性没有减少。在9例4级或5级非血液学毒性患者中，6例患者发生发热性中性粒细胞减少（FN）。FN患者年龄均>70岁。年龄>70岁患者的不良事件发生率显著高于年轻患者。总之，在接受奈达铂和伊立替康联合化疗的患者中，开始化疗前进行UGT 1A1多态性检测并不能降低不良事件的发生率。因此，单独的UGT1A1多态性检测可能不足以预测严重不良事件的发生，有效管理不良事件可能更重要，特别是在老年患者中。
An association between UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) polymorphisms and irinotecan-induced neutropenia has been previously reported. In this study, we assessed the clinical usefulness of testing for UGT1A1 polymorphisms prior to the initiation of irinotecan-based chemotherapy, as this remains a controversial subject. A total of 136 lung cancer patients who were treated with a combination of nedaplatin and irinotecan as initial chemotherapy were assessed. Following exclusion of patients exhibiting low UGT1A1 enzyme activity, 70 patients were treated after UGT1A1 polymorphism testing (test group) and 66 patients were treated without UGT1A1 polymorphism testing (non-test group). We retrospectively analyzed and compared the adverse events between the test and the non-test groups and observed no reduction in hematological or non-hematological toxicities in the test group compared to that in the non-test group. Of the 9 patients with grade 4 or 5 non-hematological toxicity, 6 patients had febrile neutropenia (FN). All the patients with FN were aged >70 years. The incidence of adverse events was significantly higher among patients aged >70 years compared to that among younger patients. In conclusion, in patients treated with nedaplatin and irinotecan combination chemotherapy, UGT1A1 polymorphism testing prior to the initiation of chemotherapy did not reduce the incidence of adverse events. Therefore, UGT1A1 polymorphism testing alone may not be sufficient to predict the occurrence of severe adverse events and it may be more important to effectively manage adverse events, particularly in elderly patients.