The association between UGT1A1 polymorphisms and treatment toxicities of liposomal irinotecan

Risk Factors for Adverse Events of Nanoliposomal Irinotecan Plus 5-Fluorouracil and L-leucovorin

“…Thus, the lower incidence of grade ≥3 neutropenia found in this study might be associated with a reduced treatment dose. The incidence of grade ≥3 neutropenia in a previous study has been reported to be significantly higher in patients with UGT1A1*6 or *28 homozygosity/compound heterozygosity than in those with single heterozygosity/wild type; occurrence rates are 73.3 and 38.1%, respectively (16). Patients with UGT1A1*6 and *28 genotypes have demonstrated decreased metabolic activity (12,13).…”

“…This study did not extract any risk factors that significantly influenced the development of diarrhea during nal-IRI/FL treatment (Table II). A previous study has revealed a significantly higher incidence of grade ≥3 diarrhea in patients with UGT1A1*6 or *28 homozygosity/compound heterozygosity than in those with single heterozygosity/wild type at 33.3% versus 9.5%, respectively (16). This study surveyed the incidence of grade ≥1 diarrhea, and we excluded seven cases because of regular loperamide administration from the start of nal-IRI/FL.…”

“…In the Japanese clinical study, all patients with UGT1A1 (UGT1A1*6/*6 or *6/*28) mutations in the nal-IRI/FL arm exhibited grade ≥3 decreased neutrophil count in spite of the dose reduction (15). A previous study in Taiwan has revealed a significantly higher incidence of grade ≥3 neutropenia and diarrhea in patients with UGT1A1*6 or *28 homozygosity/compound heterozygosity than in those with single heterozygosity/wild type (16). However, no study has reported the risk factors for the adverse events during nal-IRI/FL treatment based on analysis of factors other than the UGT1A1 polymorphism in clinical settings.…”

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer

“…The experts from JSMO also proposed the addition of a new recommendation, ‘recommendation 1l’ below and Table 1 , based on data from several Asian studies regarding irinotecan toxicity. 87 , 88 , 89 , 90 , 91 , 92 , 93 Genetic variations within the UDP glucuronosyltransferase 1 family, polypeptide A1 ( UGT1A1 ) gene have been associated with the development of certain drug toxicities, with the UGT1A1 ∗ 6 variant, common in Asian populations. 93 UGT1A1 gene polymorphisms are predictive of irinotecan-related side-effects, including diarrhoea, neutropaenia and vomiting.…”

“… 87 , 88 , 89 , 90 , 91 , 92 , 93 Genetic variations within the UDP glucuronosyltransferase 1 family, polypeptide A1 ( UGT1A1 ) gene have been associated with the development of certain drug toxicities, with the UGT1A1 ∗ 6 variant, common in Asian populations. 93 UGT1A1 gene polymorphisms are predictive of irinotecan-related side-effects, including diarrhoea, neutropaenia and vomiting. A systematic review and meta-analysis has shown the increased risk of severe neutropaenia in cancer patients with UGT1A1∗6 polymorphisms.…”