UGT1A1 Gene Polymorphism in FOLFIRI±αTherapy:Initial Dose, Relative Dose Intensity, and Side Effects Observed / 日本農村医学会雑誌

ABSTRACT

Indices for dose regulation for irinotecan (CPT-11) toxicity are diarrhea, reduction in neutrophil (NEUT) count, and level of UDP-glucuronyltransferase (UGT), which is involved in conjugation of the active metabolite SN-38. An association with the glucuronosyltransferase (UGT) 1A1 gene polymorphism has been reported. Therefore, we investigated UGT1A1 gene polymorphism and the incidence of side effects in patients who received FOLFIRI±αat our institution from November 2008 to March 2017. UGT1A1 genetic testing was performed, and 25 cases treated with FOLFIRI±αwere included. Age, sex, height, weight, and body surface area (BSA)were analyzed. UGT1A1 genotype was determined as follows:*1/*6 heterozygous (*6 he genotype), *1/*28 heterozygous (*28 he genotype), homozygous, and compound heterozygous (compound genotype). We also investigated the combination drugs (classified as he genotype) and wild type. In addition, the initial dose of CPT-11/5-FU bolus, initial relative dose intensity (RDI) (％), and blood toxicity in the first course were investigated. Mean age was 70.4±8.6 years, UGT1A1 genotype was*28 he in 5 cases, *6 he in 6 cases, and wild type in 14 cases. There were no cases of compound he or homo type. There was no significant difference between the initial dose and the initial RDI. Reduction in leukocyte count was seen in 2 cases with Grade(G)3*6 he and in 2 cases with G4*28 he. Platelet count was reduced in 2 cases with G4*28 he, 2 cases with G4*2 he, 2 cases with G4*28 he, and in 2 cases with*6 he. In this study, there was no significant difference in the initial dose and initial RDI for*6 he, *28 he, and wild type. However, *28 he and *6 he showed hematologic toxicity of G3 or more. Also, the frequency of the he genotype tended to be higher than that of wild type. Thus, it is necessary to clarify the significance of weight loss in the he type in future.