Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma

Francesco Papadia, Valeria Basso, Roberto Patuzzo, Andrea Maurichi, Annabella Di Florio, Luciano Zardi, Elisa Ventura, Reinerio González-Iglesias, Valeria Lovato, Leonardo Giovannoni, Annaelisa Tasciotti, Dario Neri, Mario Santinami, Hans D. Menssen, Franco De Cian

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Background: L19-TNF is a tumor-targeting immunocytokine composed of the human L19 antibody binding to extra domain B (ED-B) of fibronectin of newly formed blood vessels, and of human TNF. This exploratory trial evaluates safety and clinical activity of L19-TNF plus melphalan-containing isolated limb perfusion (ILP) in extremity melanoma patients. Methods: Seven and 10 patients received 325 μg and 650 μg of L19-TNF, respectively, during the ILP. Patients were studied for safety, tolerability, and clinical activity of this experimental L19-TNF ILP procedure. Results: Non-hematologic toxicity of L19-TNF ILP was very low, but severe myelosuppression was seen in four patients. Although L19-TNF was administered at a TNF-equivalent dose of only 3.13 and 6.25% of the approved TNF (Beromun®) dose of 4 mg, L19-TNF ILP induced objective responses in 86 and 89% of patients, respectively, including a complete response (CR) in 5/10 patients treated with L19-TNF ILP at 650 μg that was durable at 12 months in four patients. No CR was seen at 325 μg of L19-TNF. Conclusions: ILP with L19-TNF had a favorable safety and a promising activity profile at a dose of 650 μg of L19-TNF, supporting the exploration of higher L19-TNF doses and a Phase II trial comparing L19-TNF ILP with standard melphalan-containing ILP.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalJournal of Surgical Oncology
Volume107
Issue number2
DOIs
Publication statusPublished - Feb 2013

Fingerprint

Melphalan
Melanoma
Fever
Extremities
Perfusion
Monoclonal Antibodies
Cytokines
Neoplasms
Proteins
Safety
Fibronectins
Blood Vessels

Keywords

  • extremity melanoma
  • targeted immunocytokine
  • vascular targeting
  • vasodisruptive therapy

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma. / Papadia, Francesco; Basso, Valeria; Patuzzo, Roberto; Maurichi, Andrea; Di Florio, Annabella; Zardi, Luciano; Ventura, Elisa; González-Iglesias, Reinerio; Lovato, Valeria; Giovannoni, Leonardo; Tasciotti, Annaelisa; Neri, Dario; Santinami, Mario; Menssen, Hans D.; De Cian, Franco.

In: Journal of Surgical Oncology, Vol. 107, No. 2, 02.2013, p. 173-179.

Research output: Contribution to journalArticle

Papadia, Francesco ; Basso, Valeria ; Patuzzo, Roberto ; Maurichi, Andrea ; Di Florio, Annabella ; Zardi, Luciano ; Ventura, Elisa ; González-Iglesias, Reinerio ; Lovato, Valeria ; Giovannoni, Leonardo ; Tasciotti, Annaelisa ; Neri, Dario ; Santinami, Mario ; Menssen, Hans D. ; De Cian, Franco. / Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma. In: Journal of Surgical Oncology. 2013 ; Vol. 107, No. 2. pp. 173-179.
@article{32d4582612e84ff487e2ad7ca517f600,
title = "Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma",
abstract = "Background: L19-TNF is a tumor-targeting immunocytokine composed of the human L19 antibody binding to extra domain B (ED-B) of fibronectin of newly formed blood vessels, and of human TNF. This exploratory trial evaluates safety and clinical activity of L19-TNF plus melphalan-containing isolated limb perfusion (ILP) in extremity melanoma patients. Methods: Seven and 10 patients received 325 μg and 650 μg of L19-TNF, respectively, during the ILP. Patients were studied for safety, tolerability, and clinical activity of this experimental L19-TNF ILP procedure. Results: Non-hematologic toxicity of L19-TNF ILP was very low, but severe myelosuppression was seen in four patients. Although L19-TNF was administered at a TNF-equivalent dose of only 3.13 and 6.25{\%} of the approved TNF (Beromun{\circledR}) dose of 4 mg, L19-TNF ILP induced objective responses in 86 and 89{\%} of patients, respectively, including a complete response (CR) in 5/10 patients treated with L19-TNF ILP at 650 μg that was durable at 12 months in four patients. No CR was seen at 325 μg of L19-TNF. Conclusions: ILP with L19-TNF had a favorable safety and a promising activity profile at a dose of 650 μg of L19-TNF, supporting the exploration of higher L19-TNF doses and a Phase II trial comparing L19-TNF ILP with standard melphalan-containing ILP.",
keywords = "extremity melanoma, targeted immunocytokine, vascular targeting, vasodisruptive therapy",
author = "Francesco Papadia and Valeria Basso and Roberto Patuzzo and Andrea Maurichi and {Di Florio}, Annabella and Luciano Zardi and Elisa Ventura and Reinerio Gonz{\'a}lez-Iglesias and Valeria Lovato and Leonardo Giovannoni and Annaelisa Tasciotti and Dario Neri and Mario Santinami and Menssen, {Hans D.} and {De Cian}, Franco",
year = "2013",
month = "2",
doi = "10.1002/jso.23168",
language = "English",
volume = "107",
pages = "173--179",
journal = "Journal of Surgical Oncology",
issn = "0022-4790",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Isolated limb perfusion with the tumor-targeting human monoclonal antibody-cytokine fusion protein L19-TNF plus melphalan and mild hyperthermia in patients with locally advanced extremity melanoma

AU - Papadia, Francesco

AU - Basso, Valeria

AU - Patuzzo, Roberto

AU - Maurichi, Andrea

AU - Di Florio, Annabella

AU - Zardi, Luciano

AU - Ventura, Elisa

AU - González-Iglesias, Reinerio

AU - Lovato, Valeria

AU - Giovannoni, Leonardo

AU - Tasciotti, Annaelisa

AU - Neri, Dario

AU - Santinami, Mario

AU - Menssen, Hans D.

AU - De Cian, Franco

PY - 2013/2

Y1 - 2013/2

N2 - Background: L19-TNF is a tumor-targeting immunocytokine composed of the human L19 antibody binding to extra domain B (ED-B) of fibronectin of newly formed blood vessels, and of human TNF. This exploratory trial evaluates safety and clinical activity of L19-TNF plus melphalan-containing isolated limb perfusion (ILP) in extremity melanoma patients. Methods: Seven and 10 patients received 325 μg and 650 μg of L19-TNF, respectively, during the ILP. Patients were studied for safety, tolerability, and clinical activity of this experimental L19-TNF ILP procedure. Results: Non-hematologic toxicity of L19-TNF ILP was very low, but severe myelosuppression was seen in four patients. Although L19-TNF was administered at a TNF-equivalent dose of only 3.13 and 6.25% of the approved TNF (Beromun®) dose of 4 mg, L19-TNF ILP induced objective responses in 86 and 89% of patients, respectively, including a complete response (CR) in 5/10 patients treated with L19-TNF ILP at 650 μg that was durable at 12 months in four patients. No CR was seen at 325 μg of L19-TNF. Conclusions: ILP with L19-TNF had a favorable safety and a promising activity profile at a dose of 650 μg of L19-TNF, supporting the exploration of higher L19-TNF doses and a Phase II trial comparing L19-TNF ILP with standard melphalan-containing ILP.

AB - Background: L19-TNF is a tumor-targeting immunocytokine composed of the human L19 antibody binding to extra domain B (ED-B) of fibronectin of newly formed blood vessels, and of human TNF. This exploratory trial evaluates safety and clinical activity of L19-TNF plus melphalan-containing isolated limb perfusion (ILP) in extremity melanoma patients. Methods: Seven and 10 patients received 325 μg and 650 μg of L19-TNF, respectively, during the ILP. Patients were studied for safety, tolerability, and clinical activity of this experimental L19-TNF ILP procedure. Results: Non-hematologic toxicity of L19-TNF ILP was very low, but severe myelosuppression was seen in four patients. Although L19-TNF was administered at a TNF-equivalent dose of only 3.13 and 6.25% of the approved TNF (Beromun®) dose of 4 mg, L19-TNF ILP induced objective responses in 86 and 89% of patients, respectively, including a complete response (CR) in 5/10 patients treated with L19-TNF ILP at 650 μg that was durable at 12 months in four patients. No CR was seen at 325 μg of L19-TNF. Conclusions: ILP with L19-TNF had a favorable safety and a promising activity profile at a dose of 650 μg of L19-TNF, supporting the exploration of higher L19-TNF doses and a Phase II trial comparing L19-TNF ILP with standard melphalan-containing ILP.

KW - extremity melanoma

KW - targeted immunocytokine

KW - vascular targeting

KW - vasodisruptive therapy

UR - http://www.scopus.com/inward/record.url?scp=84872272867&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872272867&partnerID=8YFLogxK

U2 - 10.1002/jso.23168

DO - 10.1002/jso.23168

M3 - Article

C2 - 22674435

AN - SCOPUS:84872272867

VL - 107

SP - 173

EP - 179

JO - Journal of Surgical Oncology

JF - Journal of Surgical Oncology

SN - 0022-4790

IS - 2

ER -