Nemorubicin hydrochloride (nemorubicin) in combination with cisplatin (cDDP): Phase I in patients (pts) with hepatocellular carcinoma (HCC)

2572 Background: Nemorubicin is a novel DNA-intercalator with: in vivo synergistic antitumor activity with cDDP; a metabolic pathway mediated by CYP3A4 enzyme leading to formation of effective metabolites at liver level. In this phase I trial nemorubicin + cDDP are administered by intrahepatic artery every four weeks to pts with unresectable HCC to determine MTD, safety, PK profiles, CYP3A4 activity, antitumor activity. Methods: the study was in two HCC pts populations: intermediate risk (IRP) (CLIP 0–1, bilirubin <1.5 x upper normal limit, no portal vein thrombosis [PVT]); advanced risk (ARP) (CLIP 2, bilirubin <2.5 mg/dL, PVT admitted). In each population, 3–6 pts cohorts were allotted to progressively higher dose levels (DL) based on the number of dose-limiting toxicities (DLTs) in the first cycle. Results: IRP: 25 pts treated and four DL explored (range 200–600 mcg/m2 nemorubicin + 40–60 mg/m2 cDDP). DLTs were thrombocytopenia and fatigue; 600 mcg/m2 nemorubicin + 60 mg/m2 cDDP was identified as recom...