Phase II trial of nemorubicin hydrochloride (N) in combination with cisplatin (cDDP) administered by intra-hepatic artery (IHA) in patients (pts) with hepatocellular carcinoma (HCC): Final results.

Abstract

e15061 Background: N is a novel DNA-intercalator, mainly metabolized in liver by CYP3A4 enzyme and showing synergic antitumor activity with cDDP. The objective of this study was to evaluate the efficacy and toxicity of N administered by IHA in combination with cDDP to unresectable HCC pts. Methods: The study was in two HCC pt populations: advanced risk (ARP) (CLIP 2, bilirubin ≤ 2.5 mg/dL, portal vein thrombosis [PVT] admitted) and intermediate risk (IRP) (CLIP 0-1, bilirubin ≤ 1.5 x ULN, no PVT). Treatment was repeated every 4-6 wks for a maximum of 6 courses, if acceptable toxicity and no disease progression occurred. A single-arm, Simon’s Minimax two-stage design was adopted to evaluate the primary endpoint of tumour response (WHO criteria, critical numbers of responses to reject H0were ≥ 6/29 evaluable pts and ≥ 11/33 evaluable pts in ARP and IRP, respectively). Results: Thirty-seven ARP pts (27 evaluable) and 42 IRP pts (33 evaluable) were enrolled. The median number of cycles was 3 in both ARP (range 1-13; dose 400 mcg/m2 nemorubicin and 60 mg/m2 cDDP) and in IRP (range 1-6; dose 600 mcg/m2 nemorubicin and 60 mg/m2 cDDP). The trial was successful in ARP with 8 successes/27 evaluable pts (RR 30%): 7 partial responses (PR), 1 downstaging and 8 minor responses (MR)/ disease stabilization (SD) > 3 months. The IRP did not meet the efficacy criteria:2 CR, 5 PR and 13 MR/SD > 3 months (7 responses/33 evaluable pts; RR 21%). Overall, the main Grade 3-4 hematological and biochemical toxicities in ARP/IRP were thrombocytopenia (28/58%), neutropenia (26/60%), aspartate aminotransferase (25/31%), alanine aminotransferase (14/23%) and bilirubin increase (17/21%). The most frequent adverse events (any Grade ≥ 20%) were fatigue (38%), nausea (35/29%), and vomiting (24/26%). Conclusions: The trial was successful in ARP but not in IRP; IHA infusion of N with cDDP showed promising activity in both IRP and ARP with a well tolerated regimen. These encouraging results warrant further investigation in HCC, specially in multinodular type. Clinical trial information: 2005-000731-26.