UGT1A1 and Irinotecan
UDP-glucuronosyltransferase 1A1 (UGT1A1) conjugates the active metabolite of irinotecan to a glucuronide metabolite. Its activity is reduced in patients with the variant allele UGT1A1*28.
Homozygosity of this allele is found in 10% of the population.
In a number of studies, patients treated with irinotecan who were homozygous UGT1A1*28 were found to be at an increased risk of neutropenia and other toxicities related to increased blood levels. A reduced initial dose should be considered for patients found to be homozygous for the variant allele. Although heterozygous patients may be at increased risk for neutropenia, clinical results have been variable.
In July 2005, the FDA approved revisions to the safety labelling for Irinotecan-HCl injection to recommend reduced dosing in patients who are homozygous for the UGT1A1*28 allele.
| Specimen Required: | 4 mls whole blood in EDTA |
| Assay Performed: | Twice per week |
| Medicare Rebate: | No |