Annals of Surgical Oncology Cite Track
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
10.1245/s10434-006-9208-4
Annals of Surgical Oncology 14:795-801 (2007)
© 2007 Society of Surgical Oncology
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brunstein, F.
Right arrow Articles by ten Hagen, T. L. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brunstein, F.
Right arrow Articles by ten Hagen, T. L. M.

Original Article

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

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

Department of Surgical Oncology, Erasmus MC, Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands

Correspondence: Address correspondence and reprint requests to: Flavia Brunstein, MD, Department of Surgical Oncology, Laboratory of Experimental Surgical Oncology, Room Ee 0175a, PO Box 1738, 3000 DR Rotterdam, The Netherlands; E-mail: flis_br{at}yahoo.com

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.

Key Words: Liver metastasis • Sarcomas • Histamine • Regional treatment




This article has been cited by other articles:


Home page
 Ann. Surg. Oncol.Home page
C. Verhoef, J. H. W. deWilt, F. Brunstein, A. W. K. S. Marinelli, B. vanEtten, M. Vermaas, G. Guetens, G. de Boeck, E. A. de Bruijn, and A. M. M. Eggermont
Isolated Hypoxic Hepatic Perfusion with Retrograde Outflow in Patients with Irresectable Liver Metastases; A New Simplified Technique in Isolated Hepatic Perfusion
Ann. Surg. Oncol., May 1, 2008; 15(5): 1367 - 1374.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the Society of Surgical Oncology.