Given the large number of colorectal cancer cases diagnosed each year, a randomized controlled trial of the effects of irinotecan dose modifications in patients with colorectal cancer based on their UGT1A1 genotype is feasible and could clarify the tradeoffs between possible reductions in severe neutropenia and improved tumor response and/or survival in patients with various UGT1A1 genotypes.
We conducted a pragmatic prospective cohort study to establish the relevance of UGT1A1 variants in the prediction of severe diarrhea and neutropenia in patients with colorectal cancer receiving irinotecan in a routine clinical setting.
Irinotecan toxicity in patients who have colorectal cancer has been linked to reduced activity of uridine diphosphate-glucuronyltransferase 1A1 (UGT1A1).
The current data suggested that the UGT1A1*28 polymorphism may be a key determinant for predicting irinotecan-induced severe toxicities without affecting treatment outcome for patients with metastatic CRC.
In conclusion, carriage of the UGT1A7*3 allele, as well as variant-211 UGT1A1 allele represents a risk factor for the development of, and a determinant for, metastases associated with CRC patients.