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Life-threatening toxicities in a patient with UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes after irinotecan-based chemotherapy.
- Source :
-
Cancer Chemotherapy & Pharmacology . May2009, Vol. 63 Issue 6, p1165-1169. 5p. - Publication Year :
- 2009
-
Abstract
- <bold>Introduction: </bold>To explore severe toxicities induced by irinotecan-based chemotherapy and UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes. <bold>Case Report: </bold>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. <bold>Conclusion: </bold>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]
Details
- Language :
- English
- ISSN :
- 03445704
- Volume :
- 63
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Cancer Chemotherapy & Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 105489781
- Full Text :
- https://doi.org/10.1007/s00280-008-0864-x