Value of plasma SN-38 levels and DPD activity in irinotecan-based individualized chemotherapy for advanced colorectal cancer with heterozygous type UGT1A1(*)6 or UGT1A1(*)28

PURPOSE: The relationship between the pharmacokinetics of irinotecan and outcomes of advanced colorectal cancer is unclear, and few studies have examined individualized irinotecan-based chemotherapy depending on plasma 7-ethyl-10-hydroxy camptothecin (SN-38) levels and dihydropyrimidine dehydrogenase (DPD) activity, particularly for the UGT1A1(*)6 or UGT1A1(*)28 heterozygous type. METHODS: This study retrospectively explored the relationship among plasma SN-38 level 1.5 hours after critical enzyme for irinotecan (CPT-11) administration (C(SN-38 1.5h)), plasma SN-38 level 49 hours after CPT-11 administration (C(SN-38 49h)), DPD activity, and clinical outcomes for the UGT1A1(*)6 and UGT1A1(*)28 heterozygous types. RESULTS: C(SN-38 1.5h) and C(SN-38 49h) of the UGT1A1(*)6 or UGT1A1(*)28 heterozygous type were close to those of UGT1A1(*)6 and UGT1A1(*)28 wild-types; some of those with relatively high C(SN-38 1.5h) levels obtained better median progression-free survival (mPFS), whereas others with higher C(SN-38 49h) concentrations showed a relatively high incidence of adverse reactions possibly because of the decreased activity of DPD. CONCLUSION: Increasing the dosage of CPT-11 according to C(SN-38 1.5h) may improve the efficacy in patients with lower C(SN-38 1.5h) levels. For cases with comparably low DPD activity, advisable primary and subsequent dose adjustment of 5-fluorouracil based on plasma 5-fluorouracil levels may be a practical strategy for reducing the occurrence of adverse reactions for personalized treatment of the UGT1A1(*)6 or UGT1A1(*)28 heterozygous type.