Abstract
2577 Background: Amrubicin (AMR) is an active agent for lung cancer; however, substantial variability of its hematological toxicity has been observed. Genetic polymorphisms that correlate with PK/PD variabilities of AMR have not been elucidated. The aim of this study was to assess whether genetic polymorphisms correlate with PK/PD of AMR. Methods: AMR (40mg/m2) was administered on days 1-3 every 3-4 weeks with full PK samplings. DNA samples were extracted from peripheral blood mononuclear cells before treatment and 1,936 SNPs in 225 genes coding for a wide category of drug metabolizing enzymes and transporters were analyzed (DMET Plus Premier Pack). Results: Twenty-one patients with lung cancer were enrolled. Major toxicity was hematological and grade 4 neutropenia was observed in 13 out of 21 (61.9%) patients. Grade 4 neutropenia was significantly correlated with AMR (p=0.022) and its active metabolite amrubicinol (AMR-OH) clearance (CL) (p=0.004). Body-weight and serum total bilirubin were significantly...
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