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

Background: Uridine diphosphate glucuronosyltransferase (UGT) IAI 7/7 polymorphism has been linked with an increased risk of irinotecan-induced severe toxicities. We evaluated UGTIAI 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 UGT I A I genotyping in an exploratory study. The frequency of UGT I A 1 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 UGT I A 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 UGTIAI 7/7 polymorphism. Conclusion: Uridine diphosphate glucuronosyltransferase IAI 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 UGTIAI as well as UGTIAI-based dosing in patients receiving irinotecan.