Pharmacogenetic Study of Trabectedin-Induced Severe Hepatotoxicity in Patients with Advanced Soft Tissue Sarcoma.

ABSTRACT: Hepatotoxicity is an important concern for nearly 40% of the patients treated with trabectedin for advanced soft tissue sarcoma (ASTS). The mechanisms underlying these liver damages have not yet been elucidated but they have been suggested to be related to the production of reactive metabolites. The aim of this pharmacogenetic study was to identify genetic variants of pharmacokinetic genes such as CYP450 and ABC drug transporters that could impair the trabectedin metabolism in hepatocytes. Sixty-three patients with ASTS from the TSAR clinical trial (NCT02672527) were genotyped by next-generation sequencing for 11 genes, and genotype-toxicity association analyses were performed with R package SNPassoc. Among the results, ABCC2 c.1249A allele (rs2273697) and ABCG2 intron varian

SUBMITTER: Maillard M 

PROVIDER: S-EPMC7761985 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature