Case Report
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World J Gastroenterol. Jun 28, 2013; 19(24): 3899-3903
Published online Jun 28, 2013. doi: 10.3748/wjg.v19.i24.3899
Severe irinotecan-induced toxicity in a patient with UGT1A1*28 and UGT1A1*6 polymorphisms
Jian-Ming Xu, Yan Wang, Fei-Jiao Ge, Li Lin, Ze-Yuan Liu, Manish R Sharma
Jian-Ming Xu, Yan Wang, Fei-Jiao Ge, Li Lin, Affiliated Hospital Cancer Center, Academy of Military Medical Science, Beijing 100071, China
Ze-Yuan Liu, Clinical Pharmacokinetic Laboratory, Affiliated Hospital, Academy of Military Medical Science, Beijing 100071, China
Manish R Sharma, Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637-1470, United States
Author contributions: Xu JM designed research; Wang Y analzed the pharmacokinetic and clinical data; Ge FJ and Lin L collected clinical data; Liu ZY analyzed pharmacokinetic data; Xu JM and and Sharma MR wrote the paper; all authors read and approved the final manuscript.
Supported by National Natural Science Foundation Project, Grants No. 30971579; and Capital Development Foundation, No. 2007-2029
Correspondence to: Jian-Ming Xu, MD, Department of GI Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, No. 8 Dongda Avenue, Fengtai District, Beijing 100071, China. jmxu2003@yahoo.com
Telephone: +86-10-51128358 Fax: +86-10-51128358
Received: March 8, 2013
Revised: April 24, 2013
Accepted: May 8, 2013
Published online: June 28, 2013
Abstract

Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bearing 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 UGT1A1*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 UGT1A1*6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinotecan 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 irinotecan. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1*28 and UGT1A1*6 polymorphisms.

Keywords: Irinotecan, Toxicity, UGT1A1*28, UGT1A1*6, Polymorphism

Core tip: This is the first reported case. This patient with heterozygous UGT1A1*28 and UGT1A1*6 polymorphisms experienced two dose reductions of irinotecan due to severe toxicity according to pharmacokinetic analyses of SN-38 and SN-38 glucuronide levels. It seems that this patient benefited from a longer treatment duration, suggesting that irinotecan dose individualization for mutant metastatic colorectal cancer patients with heterozygous UGT1A1*28 or UGT1A1*6 polymorphisms may be warranted.