1. Life-threatening toxicities in a patient with UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes after irinotecan-based chemotherapy.
- Author
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Takane H, Kawamoto K, Sasaki T, Moriki K, Kitano H, Higuchi S, Otsubo K, Ieiri I, Takane, Hiroshi, Kawamoto, Katsuyuki, Sasaki, Tomohiro, Moriki, Kuniaki, Moriki, Kazuyo, Kitano, Hiroya, Higuchi, Shun, Otsubo, Kenji, and Ieiri, Ichiro
- 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. [ABSTRACT FROM AUTHOR]- Published
- 2009
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