Isolation limb perfusion with tumor necrosis factor alpha and chemotherapy for advanced extremity soft tissue sarcomas.

Détails

ID Serval
serval:BIB_4671
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Isolation limb perfusion with tumor necrosis factor alpha and chemotherapy for advanced extremity soft tissue sarcomas.
Périodique
Seminars in Oncology
Auteur(s)
Eggermont A.M., Schraffordt Koops H., Klausner J.M., Liénard D., Kroon B.B., Schlag P.M., Ben-Ari G., Lejeune F.J.
ISSN
0093-7754 (Print)
ISSN-L
0093-7754
Statut éditorial
Publié
Date de publication
1997
Peer-reviewed
Oui
Volume
24
Numéro
5
Pages
547-555
Langue
anglais
Notes
Publication types: Clinical Trial ; Controlled Clinical Trial ; Journal Article ; Multicenter Study
Publication Status: ppublish
Résumé
The unique property of high dose recombinant tumor necrosis factor alpha (rTNF alpha) is to activate and selectively destroy the tumor-associated microvasculature. For the systemic application of rTNF alpha it has been shown that the maximum tolerated dose (MTD) is 10 times less than the effective dose in animals. The main toxicity corresponds to systemic inflammatory response syndrome with a decrease in vascular resistance and hypotension. We found that it is possible to administer rTNF alpha at 10 times the MTD in an isolated limb perfusion (ILP) system with heart-lung machine, for locally advanced extremity soft tissue sarcomas. One hundred forty patients received an ILP with high-dose TNF alpha. In 55 patients treated with the combination of high-dose rTNF alpha + interferon-gamma + melphalan an overall objective response rate of 87% with 36% complete responses was observed; it was 81% and 28%, respectively, in a group treated with TNF alpha and melphalan (n = 85). Angiographic and immunohistological studies showed the selective and early damage of the sarcoma-associated microvasculature preceded by the upregulation of adhesion molecules and intratumoral leak of von Willebrand factor. Tumor invasion by platelets and, in some cases, by polymorphonuclear cells, appeared within hours after the application of rTNFa long before the lysis of the tumor. Thus, ILP with high-dose TNF alpha and chemotherapy seems to act through a dual targeting: TNF hits the tumor associated vasculature, and chemotherapy attacks the tumor cells. Therefore, ILP with TNF is a new option in the management of locally advanced soft tissue sarcoma of the extremities.
Mots-clé
Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Chemotherapy, Cancer, Regional Perfusion, Drug Administration Schedule, Extremities, Female, Heart-Lung Machine, Humans, Hyperthermia, Induced, Interferon-gamma/administration & dosage, Male, Melphalan/administration & dosage, Middle Aged, Recombinant Proteins/therapeutic use, Sarcoma/drug therapy, Survival Analysis, Treatment Outcome, Tumor Necrosis Factor-alpha/administration & dosage, Tumor Necrosis Factor-alpha/therapeutic use
Pubmed
Web of science
Création de la notice
19/11/2007 13:40
Dernière modification de la notice
03/03/2018 16:47
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