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 language | English |
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Pages (from-to) | 58-63 |
Number of pages | 6 |
Journal | British Journal of Cancer |
Volume | 108 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 15 2013 |
Keywords
- NGR hTNF
- pharmacodynamic
- vascular targeting agent
ASJC Scopus subject areas
- Cancer Research
- Oncology