Integration of DNA sequencing with population pharmacokinetics to improve the prediction of irinotecan exposure in cancer patients.

ABSTRACT:

Background

Irinotecan (CPT-11) is an anticancer agent widely used to treat adult solid tumours. Large interindividual variability in the clearance of irinotecan and SN-38, its active and toxic metabolite, results in highly unpredictable toxicity.

Methods

In 217 cancer patients treated with intravenous irinotecan single agent or in combination, germline DNA was used to interrogate the variation in 84 genes by next-generation sequencing. A stepwise analytical framework including a population pharmacokinetic model with SNP- and gene-based testing was used to identify demographic/clinical/genetic factors that influence the clearance of irinotecan and SN-38.

Results

Irinotecan clearance was influenced by rs4149057 in SLCO1B1, body surface area, and co-administration of 5-f

SUBMITTER: Karas S 

PROVIDER: S-EPMC8854585 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature