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01-02-2007

Synergistic Antitumor Effects of Histamine Plus Melphalan in Isolated Hepatic Perfusion for Liver Metastases

Authors: Flavia Brunstein, MD, Alexander M. M. Eggermont, MD, PhD, Gisela aan de Wiel-Ambagtsheer, Sandra T. van Tiel, Joost Rens, Timo L. M. ten Hagen, PhD

Published in: Annals of Surgical Oncology | Issue 2/2007

Abstract

Background

Nonresectable primary and metastatic liver tumors remain an important clinical problem. Melphalan-based isolated hepatic perfusion (M-IHP) leads to more than 70% objective responses in selective groups of patients with nonresectable metastases confined to the liver. Complete responses are rare and progression-free survival is limited. Tumor necrosis factor (TNF), a very active agent in isolated limb perfusion, is linked to serious hepatotoxicity, restricting its use in IHP. Because of its vasoactive properties, histamine (Hi) is an alternative to TNF. In this article we evaluate its potential synergistic effect in M-IHP, improving response rates.

Methods

Our experimental rat IHP model is used for the treatment of soft tissue sarcoma liver metastases. Blood samples are collected for monitoring liver enzymes. Livers are excised 72 h and 7 days after treatment for histologic evaluation.

Results

After sham-IHP and Hi-IHP, tumor progression was observed in 100% of treated animals, while after M-IHP this number fell to 62% and after Hi + M-IHP it fell to only 22% (P = 0.006). Overall response rates were of 55% for Hi + M-IHP vs. 25% for M-IHP, and, more importantly, complete responses (CR) were observed only after Hi + M-IHP (22%) (P = 0.009). Hepatotoxicity peaked within 24 h after IHP, independent of the treatment administered, recovered in 48 h, and was related mainly to the elevation of transaminases (grade 3 ASAT and grade 1 ALAT for control group and grades 3 and 4, respectively, for all other treatments). No serious systemic toxicity was observed. Histology of the liver showed no serious damage.

Conclusion

Hi + M-IHP has synergistic antitumor effects without any increase in regional or systemic toxicity.

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Title: Synergistic Antitumor Effects of Histamine Plus Melphalan in Isolated Hepatic Perfusion for Liver Metastases
Authors: Flavia Brunstein, MD
Alexander M. M. Eggermont, MD, PhD
Gisela aan de Wiel-Ambagtsheer
Sandra T. van Tiel
Joost Rens
Timo L. M. ten Hagen, PhD
Publication date: 01-02-2007
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 2/2007
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-006-9208-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Synergistic Antitumor Effects of Histamine Plus Melphalan in Isolated Hepatic Perfusion for Liver Metastases

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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