Increased frequency of uridine diphosphate glucuronosyltransferase 1A1 7/7 in patients experiencing severe irinotecan-induced toxicities

Abstract

Background: Uridine diphosphate glucuronosyltransferase (UGT) 1A1 7/7 polymorphism has been linked with an increased risk of irinotecan-induced severe toxicities. We evaluated UGT1A1 polymorphism in patients developing grade 3/4 toxicity after initiation of irinotecan to determine the frequency of this polymorphism in this population.

Patients and methods: Twenty patients with grade 3/4 irinotecan-induced toxicity underwent UGT1A1 genotyping in an exploratory study. The frequency of UGT1A1 7/7 and the pattern of toxicity associated with this polymorphism were described.

Results: Forty percent of patients with grade 3/4 toxicities had a UGT1A 7/7 polymorphism (vs. 10% in general population). Six of 7 patients requiring hospitalization, 7 of 10 patients with grade 4 neutropenia, and 3 of 3 patients with grade 4 diarrhea, had UGT1A1 7/7 polymorphism.

Conclusion: Uridine diphosphate glucuronosyltransferase 1A1 7/7 is prevalent in patients with irinotecan grade 3/4 toxicity, especially in patients with treatment-related hospitalizations and grade 4 toxicities. Our data support the need for more prospective studies that evaluate the predictive value of UGT1A1 as well as UGT1A1-based dosing in patients receiving irinotecan.