Effect of the CYP3A5 and ABCB1 genotype on exposure, clinical response and manifestation of toxicities from sunitinib in Asian patients

The Pharmacogenomics Journal
Y L TeoA Chan

Abstract

The objective of this study was to determine the effect of the CYP3A5 and ATP binding cassette subfamily B member 1 (ABCB1) single-nucleotide polymorphisms on the disposition of sunitinib and SU12662, on clinical response, and on the manifestation of toxicities in Asian metastatic renal cell carcinoma patients. At week 4 of each treatment cycle, toxicities and plasma steady-state levels were assessed. Clinical response was assessed after two cycles. Genotyping was performed by using the PCR restriction fragment length polymorphism method. The CC genotype for ABCB1 was associated with a higher sunitinib exposure (76.81 vs 56.55 ng ml(-1), P=0.03), higher risk of all-grade rash (RR 3.00, 95% CI 1.17-7.67) and mucositis (RR 1.60, 95% CI 1.10-2.34) and disease progression than compared with the CT/TT genotype. There was a lack of association observed between the CYP3A5 polymorphism and exposure, response and toxicities. The polymorphism of ABCB1 (C3435T) has an important role in the manifestation of toxicities and drug exposure, but not polymorphism of CYP3A5.

References

Mar 15, 2000·Proceedings of the National Academy of Sciences of the United States of America·S HoffmeyerU Brinkmann
Aug 15, 2001·Clinical Pharmacology and Therapeutics·R B KimG R Wilkinson
Jun 29, 2002·Journal of the American Society of Nephrology : JASN·Michael SiegsmundHiltrud Brauch
May 21, 2003·European Journal of Clinical Pharmacology·C BalramEdmund J D Lee
Sep 6, 2005·Pharmacogenetics and Genomics·Danxin WangWolfgang Sadée
Jan 12, 2007·The New England Journal of Medicine·Robert J MotzerRobert A Figlin
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Mar 5, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Brett E HoukMichael Amantea
Jul 21, 2009·The Lancet Oncology·Martin E GoreRonald Bukowski
Sep 16, 2009·The Pharmacogenomics Journal·M CizmarikovaA Mirossay
Oct 3, 2009·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Marie-Christine Etienne-GrimaldiGérard Milano
Jan 27, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Minako SugiyamaYasutsuna Sasaki
Jan 18, 2012·CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne·Laura Eggertson
Oct 24, 2013·Cancer Chemotherapy and Pharmacology·D de WitN P van Erp
Mar 1, 2014·Asia-Pacific Journal of Clinical Oncology·Se-Hoon LeeHyun C Chung

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Citations

Feb 4, 2016·Expert Review of Molecular Diagnostics·Meta H M DiekstraHenk-Jan Guchelaar
Sep 8, 2016·Expert Opinion on Drug Metabolism & Toxicology·Ingolf Cascorbi, Anneke Nina Werk
Oct 25, 2016·Trends in Pharmacological Sciences·Claudia NeulAnne T Nies
Mar 17, 2018·Current Opinion in Supportive and Palliative Care·Petra C Bachour, Stephen T Sonis
Aug 15, 2018·International Journal of Molecular Sciences·Klarissa D JacksonMatthew J Vergne
Jun 1, 2018·Chemical Research in Toxicology·Gracia M AmayaKlarissa D Jackson

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