Clinical Observations on Associations Between the UGT1A1 Genotype and Severe Toxicity of Irinotecan

Abstract

Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia (p p<0.05. Conclusions: Our study support the conclusion that patients with a UGT1A1*28 allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the UGT1A1*28 allele (s) did not increase severe neutropenia. Higher serum of CPT-11.

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