Irinotecan is used in monotherapy or combined with other drugs for treating different cancer streams. SN-38, the active metabolite of irinotecan, is 70% inactivated by the uridine diphosphate (UDP) glucuronosyltransferase family 1 member A1 (UGT1A1) enzyme. The 6 (rs4148323) and (rs3064744) alleles in the gene encoding the enzyme lead to decreased enzyme expression and increased severe irinotecan toxicity. Carrying one or two copies of these alleles results in a UGT1A1 intermediate or poor metabolizer status (IM, PM). The Food and Drug Administration (FDA)-approved drug labels and European Medicines Agency (EMA) European Public Assessment Report (EPAR) for irinotecan recommend dose adjustments based on genotypes, but only for UGT1A1 PM patients. However, available pharmacogenetic (PGx) dosing guidelines for the -irinotecan interaction lack a consensus about considered genetic variants, genotype-translated phenotypes, and therapeutic recommendations. We aimed to describe evidence regarding the impact of the genotype in irinotecan toxicity to inform irinotecan-dosing recommendations based on possible genotypes. : A systematic review was performed to find all the Phase I clinical trials looking for the maximum tolerated dose (MTD) or dose-limiting toxicities (DLTs) of irinotecan depending on the genotype. : Toxicity-related events and the MTD of irinotecan differ among UGT1A1 normal metabolizers (NM), IM, and PM patients considering the and/or * variants. : Dose adjustments might also be recommended for UGT1A1 IM patients ( or genotypes), with a 15% dose reduction considered.