Balloon catheter hypoxic abdominal and pelvic perfusion with tumour necrosis factor-alpha, Melphalan and Mitomycin C: a pharmacokinetic study in pigs.
BACKGROUND
Addition of tumour necrosis factor-alpha (TNF) to hypoxic abdominal perfusion (HAP) and hypoxic pelvic perfusion (HPP) with chemotherapeutic agents for treatment of un-resectable malignancies may lead to similar enhanced anti-tumour effects as are observed when TNF is added to isolated limb perfusions (ILP) with Melphalan. Here, we validate the methodology of HAP and HPP using balloon catheter techniques, and investigate the distribution of TNF, Melphalan and Mitomycin C (MMC) over the regional and systemic blood compartments when applying these techniques.


METHODS
Twelve pigs underwent HAP or HPP with TNF, Melphalan and MMC for 20 min. Throughout and after the procedures blood samples were obtained from hepatic, portal and systemic blood compartments and plasma concentrations of perfused agents were determined.


RESULTS
We demonstrated that HAP and HPP result in temporary loco-regional concentration advantages of all perfused agents, although from start of perfusion significant systemic leakage occurred.


CONCLUSIONS
On basis of these results it seems that the advantage in terms of regional plasma concentration of TNF may be insufficient for TNF-mediated effects to occur, making future addition of this cytokine to these procedures in the clinical setting questionable. The observed regional concentration advantages of MMC and Melphalan, however, warrant further studies on clinical application of these agents in both settings.
van IJken
M G A
MG
Department of Experimental Surgical Oncology, Erasmus Medical Center, Daniel den Hoed Cancer Center, Groene Hilledijk 301, Rotterdam 3075 EA, The Netherlands.
de Bruijn
E A
EA
ten Hagen
T L M
TL
de Boeck
G
G
van Eijck
C H J
CH
Eggermont
A M M
AM
D000008:Abdominal Neoplasms / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D021721:Balloon Occlusion / Q000379:methods; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D000860:Hypoxia; D008558:Melphalan / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D016685:Mitomycin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D023421:Models, Animal; D010386:Pelvic Neoplasms / Q000188:drug therapy*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D016685:Mitomycin; D008558:Melphalan