Determination of the UGT1A1 polymorphism as guidance for irinotecan dose adjustment in gastric cancer treated with second-line chemotherapy

Abstract

Purpose Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) is a key enzyme in irinotecan metabolism. However, the relationship between UGT1A1 genotype and the safety and efficacy of irinotecan monotherapy in the treatment of Chinese advanced gastric cancer remains unclear. Methods A total of 110 patients were enrolled in this study. Intravenous irinotecan was administered every 3 weeks. Irinotecan dose was selected according to the polymorphism of UGT1A1*6 gene, which was divided into 3 groups: UGT1A1*6 wild-type (GG type): 125mg/m2, d1, d8; UGT1A1*6 mutant heterozygosity (GA type) 100mg/m2, d1, d8; UGT1A1*6 homozygosity mutation (AA type) 75mg/m2, d1, d8 or paclitaxel 125mg/m2, d1, d8. Results Among these 110 patients, the genotypes of UGT1A1*28 were wild-type in 78 patients (70.9%), mutant heterozygosity in 28 (25.5%) and mutant homozygosity in 4 (3.6%). UGT1A1*6 were GG in 67 cases (60.9%), GA in 35 cases (31.8%), and AA in 8 cases (7.3%). There was no significant difference in the risk of delayed diarrhea and granulocytopenia in patients with different UGT1A1*28 genotypes (P > 0.05), while there was significant difference in the risk of delayed diarrhea and granulocytopenia in patients with different UGT1A1*6 genotypes (P < 0.05). The dose intensity of irinotecan was different in patients with different subtypes of UGT1A1*6 gene. However, there were no significant differences in PFS and OS among patients with different subtypes after dose adjustment and program adjustment (P > 0.05). Conclusion Individualized treatment under the guidance of UGT1A1*6 gene polymorphism can ensure the efficacy and reduce the incidence of adverse reactions of gastric cancer patients.