Argevani Lia, Hughes Caren, Schuh Michael J
University of Florida College of Pharmacy.
Mayo Clinic Florida.
Innov Pharm. 2020 Jul 31;11(3). doi: 10.24926/iip.v11i3.3203. eCollection 2020.
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.
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. UGT1A16 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.
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.
回顾关于药物基因组学（PGx）对UGT1A1基因代谢伊立替康的影响以及基于PGx基因变异进行剂量调整的现有文献。
伊立替康是一种常用于治疗多种癌症（如转移性结直肠癌（mCRC）等）的化疗药物。UGT1A1功能降低的程度因基因型而异，因此可能需要调整伊立替康的剂量。UGT1A1纯合*28/28基因型的个体活性可能降低70%，而1/28杂合基因型个体可能仅降低30%。UGT1A16变异也可能在功能降低中起作用。28和6等位基因的发生率在不同种族人群中有所不同，因此需要调整剂量以避免毒性。
这些发现进一步丰富了现有文献，表明携带UGT1A1 28或6变异等位基因的患者从较低剂量的伊立替康中获益。然而，由于目前现有研究的异质性，需要更多证据来研究不同患者群体中的各种治疗方案，以确定最合适的给药策略。尽管其他因素以及疗效考虑可能会影响临床决策，但基因型在确定剂量时可能是一个重要因素。
