Dosage Adjustment of Irinotecan in Patients with UGT1A1 Polymorphisms: A Review of Current Literature

OBJECTIVE: To review available literature regarding pharmacogenomics (PGx) effects on the metabolism of irinotecan by the UGT1A1 gene and the resulting dose adjustments based on PGx genetic variant. SUMMARY: Irinotecan is a chemotherapy agent commonly used in treatment of various cancers such as metastatic colorectal cancer (mCRC) and others. The extent of decreased function of UGT1A1 varies based on genotype so irinotecan dose adjustments may be needed. Those with UGT1A1 homozygous *28/*28 genotype may experience 70% reduction in activity, while heterozygous genotypes with *1/*28 may only experience 30% loss. UGT1A1*6 variants may also play a role in decreased function. The incidence of *28 and *6 alleles varies among ethnic populations resulting in the need for dosage adjustments to avoid toxicities. CONCLUSION: These findings add to a growing body of literature that suggest patients with UGT1A1 *28 or *6 variant alleles benefit from lower doses of irinotecan. However, due to the heterogeneity of currently available studies, more evidence that investigates various regimens in different patient populations is needed to determine the most appropriate dosing strategies. Although other factors, as well as efficacy considerations will likely influence clinical decision making, genotype may be an important factor when determining dose.