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Cancer Chemother Pharmacol ; 63(6): 1165-9, 2009 May.
Article in English | MEDLINE | ID: mdl-18998132

ABSTRACT

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/m(2)) on days 1, 8 and 15 in combination with docetaxel (60 mg/m(2)) 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.


Subject(s)
Antineoplastic Agents, Phytogenic/adverse effects , Camptothecin/analogs & derivatives , Glucuronosyltransferase/genetics , Organic Anion Transporters/genetics , Aged , Antineoplastic Agents, Phytogenic/blood , Antineoplastic Agents, Phytogenic/pharmacokinetics , Camptothecin/adverse effects , Camptothecin/blood , Camptothecin/pharmacokinetics , Genotype , Humans , Irinotecan , Liver-Specific Organic Anion Transporter 1 , Male , Pharmacogenetics , Pharyngeal Neoplasms/drug therapy , Pharyngeal Neoplasms/genetics
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