Pharmacogenomics and functional imaging to predict irinotecan pharmacokinetics and pharmacodynamics: the predict IR study.
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Australia
Colorectal Neoplasms
/ drug therapy
Female
Genotype
Humans
Irinotecan
/ pharmacokinetics
Liver
/ drug effects
Male
Middle Aged
Pharmacogenetics
/ methods
Polymorphism, Single Nucleotide
/ genetics
Progression-Free Survival
DMET
Hepatic functional imaging
Irinotecan
Pharmacodynamics
Pharmacokinetics
Journal
Cancer chemotherapy and pharmacology
ISSN: 1432-0843
Titre abrégé: Cancer Chemother Pharmacol
Pays: Germany
ID NLM: 7806519
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
03
12
2020
accepted:
16
03
2021
pubmed:
24
3
2021
medline:
21
9
2021
entrez:
23
3
2021
Statut:
ppublish
Résumé
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). 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- N = 31 pts. The two most significant associations between PK and PD with gene variants or HNI parameters (P < 0.05) included: (1) PK: SN38-Metabolic Ratio with CL Exploratory associations were observed between Irinotecan PK/PD with hepatic functional imaging and extensive pharmacogenomics. Further work is required to confirm and validate these findings in a larger cohort of patients. ACTRN12610000897066, Date registered: 21/10/2010.
Identifiants
pubmed: 33755789
doi: 10.1007/s00280-021-04264-8
pii: 10.1007/s00280-021-04264-8
doi:
Substances chimiques
Irinotecan
7673326042
Banques de données
ANZCTR
['ACTRN12610000897066']
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
39-52Subventions
Organisme : Australian National Health and Medical Research Council
ID : 628564
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