A phase I pharmacokinetic study of belinostat in patients with advanced cancers and varying degrees of liver dysfunction.
Naoko TakebeJan H BeumerShivaani KummarBrian F KieselAfshin DowlatiGeraldine O'Sullivan CoyneRichard PiekarzLawrence RubinsteinLaura K FogliUlka VaishampayanSanjay GoelCindy L O'BryantBassel F El-RayesVincent ChungHeinz-Josef LenzRichard KimChandra P BelaniJoseph M TuscanoWilliam SchelmanNancy MooreJames H DoroshowAlice P ChenPublished in: British journal of clinical pharmacology (2019)
While a statistically significant difference in clearance indicates increased belinostat exposure with worsening liver function, no relationship was observed between belinostat exposure and toxicity. An assessment of belinostat metabolites revealed significant differences in metabolic pathway capability in patients with differing levels of liver dysfunction. Further studies are needed to establish formal dosing guidelines in this patient population.