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.
© 2017 American Society for Clinical Pharmacology and Therapeutics.
Publication types
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Research Support, Non-U.S. Gov't
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Validation Study
MeSH terms
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / adverse effects*
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Camptothecin / administration & dosage
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Camptothecin / adverse effects
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Camptothecin / analogs & derivatives*
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Colorectal Neoplasms* / drug therapy
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Colorectal Neoplasms* / pathology
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Cost-Benefit Analysis
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Drug-Related Side Effects and Adverse Reactions* / economics
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Drug-Related Side Effects and Adverse Reactions* / genetics
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Drug-Related Side Effects and Adverse Reactions* / therapy
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Female
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Fluorouracil / administration & dosage
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Fluorouracil / adverse effects
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Glucuronosyltransferase / genetics*
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Humans
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Irinotecan* / administration & dosage
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Irinotecan* / adverse effects
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Irinotecan* / pharmacokinetics
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Italy
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Leucovorin / administration & dosage
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Leucovorin / adverse effects
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Male
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Middle Aged
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Neoplasm Staging
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Patient Care Management / economics
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Patient Care Management / methods
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Pharmacogenomic Testing* / economics
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Pharmacogenomic Testing* / methods
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Pharmacogenomic Variants / genetics
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Retrospective Studies
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Topoisomerase I Inhibitors / administration & dosage
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Topoisomerase I Inhibitors / adverse effects
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Topoisomerase I Inhibitors / pharmacokinetics
Substances
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Topoisomerase I Inhibitors
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Irinotecan
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UGT1A1 enzyme
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Glucuronosyltransferase
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Leucovorin
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Fluorouracil
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Camptothecin