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.

CONCLUSION:

NGR-hTNF was well tolerated and showed single-agent activity in HCC. Further investigation in HCC is of interest.

• Authors: A Santoro, T Pressiani, G Citterio, G Rossoni, G Donadoni, F Pozzi, L Rimassa, N Personeni, S Bozzarelli, G Rossoni, S Colombi, F G De Braud, F Caligaris-Cappio, A Lambiase, C Bordignon
• Journal: British journal of cancer (Br J Cancer) Vol. 103 Issue 6 Pg. 837-44 (Sep 07 2010) ISSN: 1532-1827 [Electronic] England
• PMID: 20717115 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Angiogenesis Inhibitors
• NGR peptide
• Oligopeptides
• Tumor Necrosis Factor-alpha

Topics

• Adult
• Aged
• Angiogenesis Inhibitors (therapeutic use)
• Carcinoma, Hepatocellular (blood supply, drug therapy)
• Female
• Humans
• Liver Neoplasms (blood supply, drug therapy)
• Male
• Middle Aged
• Neovascularization, Pathologic (drug therapy)
• Oligopeptides (adverse effects, therapeutic use)
• Tumor Necrosis Factor-alpha (adverse effects, therapeutic use)