TY - JOUR
T1 - Life-threatening toxicities in a patient with UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes after irinotecan-based chemotherapy
AU - Takane, Hiroshi
AU - Kawamoto, Katsuyuki
AU - Sasaki, Tomohiro
AU - Moriki, Kuniaki
AU - Moriki, Kazuyo
AU - Kitano, Hiroya
AU - Higuchi, Shun
AU - Otsubo, Kenji
AU - Ieiri, Ichiro
N1 - Funding Information:
Acknowledgments This study is supported by Health and Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare, Tokyo, Japan.
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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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U2 - 10.1007/s00280-008-0864-x
DO - 10.1007/s00280-008-0864-x
M3 - Article
C2 - 18998132
AN - SCOPUS:63949084512
SN - 0344-5704
VL - 63
SP - 1165
EP - 1169
JO - Cancer chemotherapy and pharmacology
JF - Cancer chemotherapy and pharmacology
IS - 6
ER -
