Examination of Factors Affecting Adverse Reactions and Dosage Reduction in UGT1A1 Genotyped Patients: A Retrospective Survey of Irinotecan

Abstract

Our aim was to clarify the side effects of irinotecan which occurred in patients admitted to Showa University Hospital to investigate whether the UGT1A1 genetic polymorphism status was reflected in the discontinuation or dose reduction of irinotecan. We retrospectively investigated UGT1A1 genetic polymorphisms, irinotecan dosage, dose discontinuance or reduction, and laboratory results from May 1 2009 to April 30 2010. The analysis of UGT1A1 genetic polymorphisms in 23 patients showed that frequencies of the UGT1A1*6 and UGT1A1*28 polymorphisms were 35% (eight patients) and 22% (five patients), respectively, and 17% (three patients) were UGT1A1*6/UGT1A1*28 compound heterozygotes. Of all patients who received irinotecan, dose reduction occurred in six patients (38%) and discontinuance in two patients (13%) due to neutropenia and other factors. Of these eight patients, seven (88%) had the UGT1A1*6 and/or *28 polymorphism. The most common irinotecan dose reduction was about 25% of the initial dose. Grade 4 neutropenia was observed in two patients who had the UGT1A1*6 and/or *28 mutation (13%), and one patient was a compound heterozygote. Our investigation confirmed that the UGT1A1 genetic polymorphism status of the patients was reflected in the discontinuance or dose reduction of irinotecan. Our results suggest that Grade 4 neutropenia may occur in patients who are compound heterozygotes and that these patients may need careful selection of treatment regimens possibly involving discontinuance or reduction in irinotecan dosage.