Impact of the UGT1A1*28 allele on response to irinotecan: a systematic review and meta-analysis.
OBJECTIVE
Pre-emptive irinotecan dose reduction for UGT1A1*28 homozygotes may result in reduced risk of severe neutropenia and diarrhea. However, clinical utility and cost-effectiveness are dependent upon such a dose reduction not impacting irinotecan efficacy. Whether UGT1A1*28 genotype is associated with irinotecan response therefore is an important gap in existing knowledge to inform clinical utility.


METHODS
A systematic review and meta-analysis was performed to analyze the difference in objective response rate (ORR) between irinotecan-administered cancer patients with different UGT1A1*28 genotypes: *28/*28 (homozygous variant), *1/*28 (heterozygous variant) or *1/*1 (wild-type). The effect of irinotecan dose on the association between UGT1A1*28 and ORR was also assessed.


RESULTS
Differences in ORR for either of the genotype comparisons, *28/*28 versus *1/*1 and *1/*28 versus *1/*1, were not statistically significant. Irinotecan dose also did not impact upon ORR differences between UGT1A1 genotype groups.


CONCLUSIONS
An individual's response to irinotecan is unlikely to be affected by UGT1A1*28 status.
University of South Australia, Division of Health Sciences, School of Pharmacy & Medical Sciences, GPO Box 2471, Adelaide, South Australia 5001, Australia.
Mafalda M
MM
Dias
Ross A
RA
McKinnon
Michael J
MJ
Sorich
D000483:Alleles; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects; D054316:Biomarkers, Pharmacological; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced; D056726:Genetic Association Studies; D014453:Glucuronosyltransferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D000077146:Irinotecan; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009503:Neutropenia / Q000139:chemically induced; D000099148:UGT1A1 Enzyme
D000972:Antineoplastic Agents, Phytogenic; D054316:Biomarkers, Pharmacological; D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme