Phase i and pharmacodynamic study of high-dose NGR-hTNF in patients with refractory solid tumours

P. A. Zucali, M. Simonelli, F. De Vincenzo, E. Lorenzi, M. Perrino, M. Bertossi, R. Finotto, S. Naimo, L. Balzarini, C. Bonifacio, I. Timofeeva, G. Rossoni, G. Mazzola, A. Lambiase, C. Bordignon, A. Santoro

Research output: Contribution to journalArticlepeer-review

Abstract

Background:NGR-hTNF exploits the peptide asparagine-glycine-arginine (NGR) for selectively targeting tumour necrosis factor (TNF) to CD13-overexpressing tumour vessels. Maximum-tolerated dose (MTD) of NGR-hTNF was previously established at 45 μg m-2 as 1-h infusion, with dose-limiting toxicity being grade 3 infusion-related reactions. We explored further dose escalation by slowing infusion rate (2-h) and using premedication (paracetamol).Methods:Four patients entered each of 12 dose levels (n=48; 60-325 μg m-2). Pharmacokinetics, soluble TNF receptors (sTNF-R1/sTNF-R2), and volume transfer constant (K trans) by dynamic imaging (dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)) were assessed pre-and post-treatment.Results:Common related toxicity included grade 1/2 chills (58%). Maximum-tolerated dose was not reached. Both C max (P

Original languageEnglish
Pages (from-to)58-63
Number of pages6
JournalBritish Journal of Cancer
Volume108
Issue number1
DOIs
Publication statusPublished - Jan 15 2013

Keywords

  • NGR hTNF
  • pharmacodynamic
  • vascular targeting agent

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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