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/m2),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 AUC0-23.25h of SN-38 was 523.6 ng·h/mL at a dose of 32.5 mg/m2 of CPT-11,which was higher than that in the literature at a dose of 100 mg/m2.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 26 mg/m2 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 26 mg/m2,324 mg/m2 and 195 mg/m2 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.
