Cost Evaluation of Irinotecan-Related Toxicities Associated With the UGT1A1*28 Patient Genotype

Clin Pharmacol Ther. 2017 Jul;102(1):123-130. doi: 10.1002/cpt.615. Epub 2017 Mar 20.

Abstract

The adoption of a preemptive UGT1A1*28 genotyping to increase irinotecan safety in clinical practice is still limited. This is the first actual study of costs associated with the management of irinotecan-related toxicities, and their association with UGT1A1*28 genotype. A retrospective analysis of the cost of toxicity management was conducted on 243 metastatic colorectal cancer patients enrolled in a clinical trial and treated with standard of care FOLFIRI (5-fluorouracil combined with irinotecan). The mean predicted cost per patient was higher for *28/*28 (€4,886), vs. *1/*1 (€812), (regression coefficient 1.79, 95% confidence interval (CI) = 1.31-2.28; P < 0.001) and for *1/*28 (€1,119) vs. *1/*1 (regression coefficient 0.32, 95% CI = 0.04-0.60; P = 0.024). This is consistent with a different grade 4 toxicity profile among the three genotypes, and a higher frequency of costly interventions like hospitalization among patients with the *28 allele. A differential toxicity management cost by *28 genotype is herein demonstrated, representing a first step towards the demonstration of the test clinical utility.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / pathology
  • Cost-Benefit Analysis
  • Drug-Related Side Effects and Adverse Reactions* / economics
  • Drug-Related Side Effects and Adverse Reactions* / genetics
  • Drug-Related Side Effects and Adverse Reactions* / therapy
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Glucuronosyltransferase / genetics*
  • Humans
  • Irinotecan* / administration & dosage
  • Irinotecan* / adverse effects
  • Irinotecan* / pharmacokinetics
  • Italy
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Patient Care Management / economics
  • Patient Care Management / methods
  • Pharmacogenomic Testing* / economics
  • Pharmacogenomic Testing* / methods
  • Pharmacogenomic Variants / genetics
  • Retrospective Studies
  • Topoisomerase I Inhibitors / administration & dosage
  • Topoisomerase I Inhibitors / adverse effects
  • Topoisomerase I Inhibitors / pharmacokinetics

Substances

  • Topoisomerase I Inhibitors
  • Irinotecan
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • IFL protocol