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

doi:10.1038/bjc.2012.506

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

Istituto Clinico Humanitas

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	58-63
Number of pages	6
Journal	British Journal of Cancer
Volume	108
Issue number	1
DOIs	https://doi.org/10.1038/bjc.2012.506
Publication status	Published - Jan 15 2013

Keywords

NGR hTNF
pharmacodynamic
vascular targeting agent

ASJC Scopus subject areas

Cancer Research
Oncology

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10.1038/bjc.2012.506

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Zucali, P. A., Simonelli, M., De Vincenzo, F., Lorenzi, E., Perrino, M., Bertossi, M., Finotto, R., Naimo, S., Balzarini, L., Bonifacio, C., Timofeeva, I., Rossoni, G., Mazzola, G., Lambiase, A., Bordignon, C., & Santoro, A. (2013). Phase i and pharmacodynamic study of high-dose NGR-hTNF in patients with refractory solid tumours. British Journal of Cancer, 108(1), 58-63. https://doi.org/10.1038/bjc.2012.506

Phase i and pharmacodynamic study of high-dose NGR-hTNF in patients with refractory solid tumours. / Zucali, P. A.; Simonelli, M.; De Vincenzo, F.; Lorenzi, E.; Perrino, M.; Bertossi, M.; Finotto, R.; Naimo, S.; Balzarini, L.; Bonifacio, C.; Timofeeva, I.; Rossoni, G.; Mazzola, G.; Lambiase, A.; Bordignon, C.; Santoro, A.

In: British Journal of Cancer, Vol. 108, No. 1, 15.01.2013, p. 58-63.

Research output: Contribution to journal › Article › peer-review

Zucali, PA , Simonelli, M , De Vincenzo, F, Lorenzi, E, Perrino, M, Bertossi, M, Finotto, R, Naimo, S, Balzarini, L, Bonifacio, C, Timofeeva, I, Rossoni, G, Mazzola, G, Lambiase, A, Bordignon, C & Santoro, A 2013, 'Phase i and pharmacodynamic study of high-dose NGR-hTNF in patients with refractory solid tumours', British Journal of Cancer, vol. 108, no. 1, pp. 58-63. https://doi.org/10.1038/bjc.2012.506

Zucali, P. A. ; Simonelli, M. ; De Vincenzo, F. ; Lorenzi, E. ; Perrino, M. ; Bertossi, M. ; Finotto, R. ; Naimo, S. ; Balzarini, L. ; Bonifacio, C. ; Timofeeva, I. ; Rossoni, G. ; Mazzola, G. ; Lambiase, A. ; Bordignon, C. ; Santoro, A. / Phase i and pharmacodynamic study of high-dose NGR-hTNF in patients with refractory solid tumours. In: British Journal of Cancer. 2013 ; Vol. 108, No. 1. pp. 58-63.

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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",

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AU - Zucali, P. A.

AU - Simonelli, M.

AU - De Vincenzo, F.

AU - Lorenzi, E.

AU - Perrino, M.

AU - Bertossi, M.

AU - Finotto, R.

AU - Naimo, S.

AU - Balzarini, L.

AU - Bonifacio, C.

AU - Timofeeva, I.

AU - Rossoni, G.

AU - Mazzola, G.

AU - Lambiase, A.

AU - Bordignon, C.

AU - Santoro, A.

PY - 2013/1/15

Y1 - 2013/1/15

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

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