title: Activity and safety of NGR-hTNF, a selective vascular-targeting agent, in previously treated patients with advanced hepatocellular carcinoma.
abstract: 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 microg m(-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.
  
  
  CONCLUSIONS
  NGR-hTNF was well tolerated and showed single-agent activity in HCC. Further investigation in HCC is of interest.
authors: Department of Oncology, Istituto Clinico Humanitas, Rozzano, Italy.
authors: A
authors: A
authors: Santoro
authors: T
authors: T
authors: Pressiani
authors: G
authors: G
authors: Citterio
authors: G
authors: G
authors: Rossoni
authors: G
authors: G
authors: Donadoni
authors: F
authors: F
authors: Pozzi
authors: L
authors: L
authors: Rimassa
authors: N
authors: N
authors: Personeni
authors: S
authors: S
authors: Bozzarelli
authors: G
authors: G
authors: Rossoni
authors: S
authors: S
authors: Colombi
authors: F G
authors: FG
authors: De Braud
authors: F
authors: F
authors: Caligaris-Cappio
authors: A
authors: A
authors: Lambiase
authors: C
authors: C
authors: Bordignon
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; C526428:NGR peptide; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha