Activity and safety of NGR-hTNF, a selective vascular-targeting agent, in previously treated patients with advanced hepatocellular carcinoma.
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.
Santoro
A
A
Department of Oncology, Istituto Clinico Humanitas, Rozzano, Italy.
Pressiani
T
T
Citterio
G
G
Rossoni
G
G
Donadoni
G
G
Pozzi
F
F
Rimassa
L
L
Personeni
N
N
Bozzarelli
S
S
Rossoni
G
G
Colombi
S
S
De Braud
F G
FG
Caligaris-Cappio
F
F
Lambiase
A
A
Bordignon
C
C
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*
D020533:Angiogenesis Inhibitors; C526428:NGR peptide; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha