Fakih Marwan G, Ross Mary Ellen, Starostik Petr
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Clin Colorectal Cancer. 2007 Jul;6(8):583-7. doi: 10.3816/CCC.2007.n.026.
BACKGROUND: Uridine diphosphate glucuronosyltransferase (UGT) 1A1 7/7 polymorphism has been linked with an increased risk of irinotecan-induced severe toxicities. We evaluated UGT1A1 polymorphism in patients developing grade 3/4 toxicity after initiation of irinotecan to determine the frequency of this polymorphism in this population. PATIENTS AND METHODS: Twenty patients with grade 3/4 irinotecan-induced toxicity underwent UGT1A1 genotyping in an exploratory study. The frequency of UGT1A1 7/7 and the pattern of toxicity associated with this polymorphism were described. RESULTS: Forty percent of patients with grade 3/4 toxicities had a UGT1A 7/7 polymorphism (vs. 10% in general population). Six of 7 patients requiring hospitalization, 7 of 10 patients with grade 4 neutropenia, and 3 of 3 patients with grade 4 diarrhea, had UGT1A1 7/7 polymorphism. CONCLUSION: Uridine diphosphate glucuronosyltransferase 1A1 7/7 is prevalent in patients with irinotecan grade 3/4 toxicity, especially in patients with treatment-related hospitalizations and grade 4 toxicities. Our data support the need for more prospective studies that evaluate the predictive value of UGT1A1 as well as UGT1A1-based dosing in patients receiving irinotecan.
背景：尿苷二磷酸葡萄糖醛酸基转移酶（UGT）1A1 7/7多态性与伊立替康诱导的严重毒性风险增加有关。我们评估了在开始使用伊立替康后发生3/4级毒性的患者中的UGT1A1多态性，以确定该多态性在该人群中的频率。 患者和方法：在一项探索性研究中，对20例发生3/4级伊立替康诱导毒性的患者进行了UGT1A1基因分型。描述了UGT1A1 7/7的频率以及与该多态性相关的毒性模式。 结果：3/4级毒性患者中有40%具有UGT1A 7/7多态性（相比之下，普通人群中为10%）。7例需要住院治疗的患者中有6例、10例4级中性粒细胞减少患者中有7例以及3例4级腹泻患者中有3例具有UGT1A1 7/7多态性。 结论：尿苷二磷酸葡萄糖醛酸基转移酶1A1 7/7在伊立替康3/4级毒性患者中普遍存在，尤其是在与治疗相关的住院患者和4级毒性患者中。我们的数据支持需要进行更多前瞻性研究，以评估UGT1A1的预测价值以及在接受伊立替康治疗的患者中基于UGT1A1的给药方案。
Pharmacogenomics J. 2010-2-23
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