Phase II study of NGR-hTNF, a selective vascular targeting agent, in patients with metastatic colorectal cancer after failure of standard therapy

Armando Santoro, Lorenza Rimassa, Alberto F. Sobrero, Giovanni Citterio, Francesco Sclafani, Carlo Carnaghi, Anna Pessino, Francesco Caprioni, Valeria Andretta, Maria Chiara Tronconi, Giovanna Finocchiaro, Gloria Rossoni, Angela Zanoni, Chiara Miggiano, Gian Paolo Rizzardi, Catia Traversari, Federico Caligaris-Cappio, Antonio Lambiase, Claudio Bordignon

Research output: Contribution to journalArticlepeer-review


Background: NGR-hTNF consists of human tumour necrosis factor (hTNF) fused with the tumour-homing peptide Asp-Gly-Arg (NGR), which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels. Preclinical antitumour activity was observed even at low doses. We evaluated the activity and safety of low-dose NGR-hTNF in colorectal cancer (CRC) patients failing standard therapies. Patients and methods: Thirty-three patients with progressive disease at study entry received NGR-hTNF 0.8 μg/m2 given intravenously every 3 weeks. The median number of prior treatment regimens was three (range, 2-5). One-quarter of patients had previously received four or more regimens and two-thirds targeted agents. Progression-free survival (PFS) was the primary study objective. Results: NGR-hTNF was well tolerated. No treatment-related grade 3 to 4 toxicities were detected, most common grade 1 to 2 adverse events being short-lived, infusion-time related chills (50.0%). One partial response and 12 stable diseases were observed, yielding a disease control rate of 39.4% (95% CI, 22.9-57.8%). Median PFS and overall survival were 2.5 months (95% CI, 2.1-2.8) and 13.1 months (95% CI, 8.9-17.3), respectively; whereas in patients who achieved disease control the median PFS and overall survival were 3.8 and 15.4 months, respectively. In an additional cohort of 13 patients treated at same dose with a weekly schedule, there was no increased toxicity and 2 patients experienced PFS longer than 10 months. Conclusion: Based on tolerability and preliminary evidence of disease control in heavily pretreated CRC patients, NGR-hTNF deserves further evaluation in combination with standard chemotherapy.

Original languageEnglish
Pages (from-to)2746-2752
Number of pages7
JournalEuropean Journal of Cancer
Issue number15
Publication statusPublished - Oct 2010


  • Colorectal cancer
  • NGR-hTNF
  • Vascular targeting agent

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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