Background:Hepatocellular carcinoma (HCC) is a highly vascularised and poor-prognosis tumour. NGR-hTNF is a vascular-targeting agent consisting of human tumour necrosis factor-alpha fused to the tumour-homing peptide NGR, which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels.Methods:Twenty-seven patients with advanced-stage disease resistant to either locoregional (59%; range, 1-3), systemic treatments (52%; range, 1-3) or both (33%) received NGR-hTNF 0.8 gm-2 once every 3 weeks. The primary aim of the study was progression-free survival (PFS).Results:No grade 3-4 treatment-related toxicities were noted. Common toxicity included mild-to-moderate, short-lived chills (63%). Median PFS was 2.3 months (95% CI: 1.7-2.9). A complete response ongoing after 20 months was observed in a sorafenib-refractory patient and a partial response in a Child-Pugh class-B patient, yielding a response rate of 7%. Six patients (22%) experienced stable disease. The disease control rate (DCR) was 30% and was maintained for a median PFS time of 4.3 months. Median survival was 8.9 months (95% CI: 7.5-10.2). In a subset of 12 sorafenib-resistant patients, the response rate was 8% and the median survival was 9.5 months.Conclusion:NGR-hTNF was well tolerated and showed single-agent activity in HCC. Further investigation in HCC is of interest.
|Titolo:||Activity and safety of NGR-hTNF, a selective vascular-targeting agent, in previously treated patients with advanced hepatocellular carcinoma|
|Parole Chiave:||hepatocellular carcinoma; NGR-hTNF; vascular-targeting agent; Adult; Aged; Angiogenesis Inhibitors; Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Middle Aged; Neovascularization, Pathologic; Oligopeptides; Tumor Necrosis Factor-alpha; Cancer Research; Oncology; Medicine (all)|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||2010|
|Digital Object Identifier (DOI):||10.1038/sj.bjc.6605858|
|Appare nelle tipologie:||01 - Articolo su periodico|