Life-threatening toxicities in a patient with UGT1A16/28 and SLCO1B115/15 genotypes after irinotecan-based chemotherapy

Introduction To explore severe toxicities induced by irinotecan-based chemotherapy and UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes. Case report A 66-year-old Japanese male diagnosed with left pharyngeal carcinoma (T2N2bM0, stage IVA) was treated with irinotecan (70 mg/m²) on days 1, 8 and 15 in combination with docetaxel (60 mg/m²) on day 1 of a 28-day cycle. After the first cycle, he suffered marked toxicities, including grade 4 diarrhea and febrile grade 4 neutropenia. Plasma concentrations of irinotecan, SN-38 and SN-38G were measured, and extensive accumulation of SN-38 was observed. Genotyping of UGT1A1 and OATP1B1 proteins showed UGT1A1*6/*28 and SLCO1B1*15/*15, respectively, which are known to lead to extremely low glucuronidation and transport activities of substrate drugs. Conclusion The severe toxicities in this patient are attributable to the extensive accumulation of SN-38, which may result from a synergistic or additive effect of low metabolic (UGT1A1*6/*28) and transport (SLCO1B1*15/*15) capabilities.