IFL療法によりgrade 4の好中球減少が認められた大腸がん患者のUGT1A1遺伝子多型と薬物体内動態解析

概要

論文の詳細を見る
We carried out a pharmacogenetic analysis on uridine diphosphate glucuronosyltransferase (UGT) 1A1 polymorphism and a pharmacokinetic analysis on irinotecan (CPT-11) and its metabolites for a patient who developed severe neutropenia after the first course of a CPT-11 (100 mg/m^2), 5-fluorouracil (5-FU) and leucovorin regimen (IFL regimen). Genotyping showed the patient to be homozygous for the UGT1A1 28 allele and heterozygous for UGT1A1 27 allele. In the pharmacokinetic analysis, the serum concentrations of CPT-11, SN-38, SN-38 glucuronide and 5-FU were measured. The AUC_<0-23.25h> of SN-38 was 523.6ng・h/mL at a dose of 32.5mg/m^2 of CPT-11, which was higher than that in the literature at a dose of 100mg/m^2. The serum concentration of 5-FU, however, was lower than that in the literature for the same dose. Lowering the dose of CPT-11 from 100 to 26mg/m^2 resulted in a decrease in CEA and CA 19-9 concentrations and a reduction in the lung metastatic focus. Considered together with the change in absolute neutrophil count observed, these findings suggested that the doses of CPT-11, 5-FU and L-leucovorin be adjusted to 26mg/m^2, 324mg/m^2 and 195mg/m^2 respectively and the washout period be extended. In conclusion, the UGT1A1 genetic analysis and follow-up monitoring of serum CPT-11 levels that we conducted facilitated the creation of a personalized IFL regimen for the patient, which improved efficacy and safety.
日本医療薬学会の論文
2008-01-10