title: Cost Evaluation of Irinotecan-Related Toxicities Associated With the UGT1A1*28 Patient Genotype.
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.
authors.affiliation: Experimental and Clinical Pharmacology, Centro Di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Roncato
authors.affiliation: Experimental and Clinical Pharmacology, Centro Di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cecchin
authors.affiliation: Experimental and Clinical Pharmacology, Centro Di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Montico
authors.affiliation: Experimental and Clinical Pharmacology, Centro Di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: De Mattia
authors.affiliation: Experimental and Clinical Pharmacology, Centro Di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Giodini
authors.affiliation: Medical Oncology Unit B, Centro Di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Buonadonna
authors.affiliation: Sanitary Direction, Centro Di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Solfrini
authors.affiliation: Eshelman School of Pharmacy, Center for Pharmacogenomics and Individualized Therapy, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: F
authors.initials: F
authors.lastname: Innocenti
authors.affiliation: Experimental and Clinical Pharmacology, Centro Di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Toffoli
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology; D003362:Cost-Benefit Analysis; D064420:Drug-Related Side Effects and Adverse Reactions / Q000191:economics / Q000235:genetics / Q000628:therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D007558:Italy; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010346:Patient Care Management / Q000191:economics / Q000379:methods; D000071185:Pharmacogenomic Testing / Q000191:economics / Q000379:methods; D000071184:Pharmacogenomic Variants / Q000235:genetics; D012189:Retrospective Studies; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D005472:Fluorouracil; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D002955:Leucovorin; D059004:Topoisomerase I Inhibitors; D000099148:UGT1A1 Enzyme