Corresponding to previous studies, simulations with the PK/PD model indicated a dose-dependent risk of severe neutropenia following irinotecan therapy, which was considerably increased in patients with reduced UGT1A1 activity (grade 4 neutropenia in wild-type/poor metabolizers: 14%/21%) (18, 24, 31). This evidence concerns the gene UGT1A1 and Decreased total neutrophil count.