Pharmacogenomics and functional imaging to predict irinotecan pharmacokinetics and pharmacodynamics: the predict IR study
Michael Michael, Winston Liauw, Sue-Anne McLachlan, Emma Link, Annetta Matera, Michael Thompson, Michael Jefford, Rod J Hicks, Carleen Cullinane, Athena Hatzimihalis, Ian G Campbell, Simone Rowley, Phillip J Beale, Christos S Karapetis, Timothy Price, Mathew E Burge
CANCER CHEMOTHERAPY AND PHARMACOLOGY | SPRINGER | Published : 2021
PURPOSE: Irinotecan (IR) displays significant PK/PD variability. This study evaluated functional hepatic imaging (HNI) and extensive pharmacogenomics (PGs) to explore associations with IR PK and PD (toxicity and response). METHODS: Eligible patients (pts) suitable for Irinotecan-based therapy. At baseline: (i) PGs: blood analyzed by the Affymetrix-DMET™-Plus-Array (1936 variants: 1931 single nucleotide polymorphisms [SNPs] and 5 copy number variants in 225 genes, including 47 phase I, 80 phase II enzymes, and membrane transporters) and Sanger sequencing (variants in HNF1A, Topo-1, XRCC1, PARP1, TDP, CDC45L, NKFB1, and MTHFR), (ii) HNI: pts given IV 250 MBq-99mTc-IDA, data derived for hepatic..View full abstract
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Awarded by Australian National Health and Medical Research Council
Funded by the Australian National Health and Medical Research Council Grant 628564.