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Severe irinotecan-induced toxicity in a patient with UGT1A1*28 and UGT1A1*6 polymorphisms

查看全文 作　　者：Jian-Ming [1]Xu;Yan [1]Wang;Fei-Jiao [1]Ge;Li [1]Lin;Ze-Yuan [2]Liu;Manish R [3]Sharma 高影响力作者 机构地区：[1]Affiliated Hospital Cancer Center, Academy of Military Medical Science;[2]Clinical Pharmacokinetic Laboratory, Affiliated Hospital,Academy of Military Medical Science;[3]Department of Medicine, Section of Hema-tology/Oncology, University of Chicago高影响力机构 出　　处：《World Journal of Gastroenterology》索引2013年第19卷第24期,共5页高影响力期刊 基　　金：Supported by National Natural Science Foundation Project,Grants No.30971579;Capital Development Foundation,No.2007-2029 摘　　要：Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bear-ing UGT1A1*28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of irinotecan are advised that patients with UGT1A1*28 (TA 7/7) should start with a reduced dose of irinotecan, although a particular dose is not specified. Research in Asian countries has shown a lower incidence of UG-T1A1*28 (TA 7/7), while UGT1A1*6 (A/A) is more often found and is associated with severe irinotecan-related neutropenia. We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1*28 polymorphism (TA 6/7) as well as the UG-T1A1*6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinote-can dose reductions according to pharmacokinetic data regarding exposure to the active metabolite, SN-38. Simultaneous heterozygous UGT1A1*28 and UGT1A1*6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinote-can. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1*28 and UGT1A1*6 polymorphisms. 关 键 词：IRINOTECAN TOXICITY UGT1A1*28 UGT1A1*6 POLYMORPHISM
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