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

H Takane, K Kawamoto, T Sasaki, K Moriki… - Cancer chemotherapy …, 2009 - Springer
H Takane, K Kawamoto, T Sasaki, K Moriki, K Moriki, H Kitano, S Higuchi, K Otsubo, I Ieiri
Cancer chemotherapy and pharmacology, 2009•Springer
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 …
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.
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