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Life-threatening toxicities in a patient with UGT1A1 * 6 /* 28 and SLCO1B1 * 15 /* 15 genotypes after irinotecan-based chemotherapy

Life-threatening toxicities in a patient with UGT1A1 * 6 /* 28 and SLCO1B1 * 15 /* 15 genotypes after irinotecan-based chemotherapy,10.1007/s00280-008

Life-threatening toxicities in a patient with UGT1A1 * 6 /* 28 and SLCO1B1 * 15 /* 15 genotypes after irinotecan-based chemotherapy   (Citations: 7)
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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.
Journal: Cancer Chemotherapy and Pharmacology - CANCER CHEMOTHER PHARMACOL , vol. 63, no. 6, pp. 1165-1169, 2009
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