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, Hiroshi, Kawamoto, Katsuyuki, Sasaki, Tomohiro, Moriki, Kuniaki, Moriki, Kazuyo, Kitano, Hiroya, Higuchi, Shun, Otsubo, Kenji, and Ieiri, Ichiro
- Subjects
PHARYNGEAL cancer ,TOXICITY testing ,CANCER patients ,DRUG therapy ,GENOTYPE-environment interaction ,NEUTROPENIA ,GENETIC polymorphisms - Abstract
To explore severe toxicities induced by irinotecan-based chemotherapy and UGT1A1* 6/* 28 and SLCO1B1* 15/* 15 genotypes. 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/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. 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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