Severe irinotecan-induced toxicity in a patient with UGT1A1*28 and UGT1A1*6 polymorphisms |
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Authors: | Jian-Ming Xu Yan Wang Fei-Jiao Ge Li Lin Ze-Yuan Liu Manish R Sharma |
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Affiliation: | Jian-Ming Xu, Yan Wang, Fei-Jiao Ge, Li Lin, Affiliated Hospital Cancer Center, Academy of Military Medical Science, Beijing 100071, ChinaZe-Yuan Liu, Clinical Pharmacokinetic Laboratory, Affiliated Hospital, Academy of Military Medical Science, Beijing 100071, ChinaManish R Sharma, Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637-1470, United States |
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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. |
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Keywords: | Irinotecan Toxicity UGT1A1*28 UGT1A1*6 Polymorphism |
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