Chemosaturation with Percutaneous Hepatic Perfusions of Melphalan for Hepatic Metastases: Experience from Two European Centers

Abstract

Purpose: Chemosaturation with percutaneous hepatic perfusion (PHP; Hepatic CHEMOSAT^® Delivery System; Delcath Systems Inc, USA) is a minimally invasive, repeatable regional therapy for unresectable hepatic metastases. It uses a system of catheters and filters to isolate hepatic venous blood from the systemic circulation, allowing delivery of high-dose chemotherapy to the hepatic artery. Effluent hepatic venous blood is filtered before being returned to the systemic circulation, thereby reducing exposure to chemotherapy. We describe our experiences with chemosaturation-PHP at 2 European centers.

Materials and Methods: 14 patients presented unresectable hepatic metastases from solid tumors; 13 received 1 – 3 sessions of chemosaturation-PHP. Melphalan 2.0 (n = 1) or 3.0 (n = 12) mg/kg was given as a 30-minute infusion into the hepatic artery. 12 patients were evaluable for tumor response.

Results: One complete (cholangiocarcinoma, n = 1) and 6 partial responses (ocular, n = 3 or cutaneous melanoma, n = 3) were observed, 5 patients had stable disease (ocular melanoma, n = 3; breast cancer, n = 1; gastric cancer, n = 1). Mild to moderate filter-related toxicity (i. e. thrombocytopenia, anemia) was observed immediately post-procedure. Grade 3/4 melphalan-related pancytopenia developed after 1 – 2 weeks. All hematological events were managed effectively with transfusions and/or other supportive measures. The new high-efficiency filter showed milder toxicity and faster recovery. In one case, chemosaturation-PHP was abandoned prematurely due to heparin-induced vaginal bleeding, and one patient died due to retroperitoneal hemorrhage from heparin anti-coagulation.

Conclusion: Chemosaturation-PHP for non-resectable liver metastases is a feasible treatment option when performed by an experienced multi-disciplinary team. It may be a promising regional therapy for patients with no effective treatment options.

Citation Format:

• Vogl TJ, Zangos S, Scholtz JE et al. Chemosaturation with Percutaneous Hepatic Perfusions of Melphalan for Hepatic Metastases: Experience from Two European Centers. Fortschr Röntgenstr 2014; 186: 937 – 944

Zusammenfassung

Ziel: Chemosaturation mit perkutaner hepatischer Perfusion (PHP; Hepatic CHEMOSAT^® Delivery System; Delcath Systems Inc, USA) ist ein minimalinvasives, wiederholbares regionales Therapieverfahren bei nicht resezierbaren Lebermetastasen, das mithilfe eines Systems aus Kathetern und Filtern das venöse hepatische Blut vom Systemkreislauf isoliert und eine hochdosierte Chemotherapeutikagabe über die hepatischen Arterien ermöglicht. Der venöse hepatische Abfluss wird zur Reduktion von Nebenwirkungen des Chemotherapeutikums vor dem Rückführen in den systemischen Kreislauf gefiltert. Wir berichten über unsere Erfahrungen mit Chemosaturation-PHP an zwei europäischen Zentren.

Material und Methoden: 14 Patienten zeigten nicht resezierbare hepatische Metastasen solider Tumore; 13 Patienten wurden in 1 – 3 Therapiesitzungen mittels Chemosaturation-PHP behandelt. Melphalan 2,0 (n = 1) und 3,0 (n = 12) mg/kg wurde 30 Minuten in die hepatischen Arterien infundiert. Für das Tumoransprechen waren 12 Patienten auswertbar.

Ergebnisse: Komplette Remission wurde in einem Patienten beobachtet (Cholangiokarzinom, n = 1), partielle Remission in 6 Patienten (Aderhautmelanom, n = 3; malignes Melanom, n = 3), 5 Patienten zeigten stable disease (Aderhautmelanom, n = 3; Brustkrebs, n = 1; Magenkarzinom, n = 1). Milde bis mäßige filterassoziierte Nebenwirkungen (z. B. Thrombozytopenie, Anämie) wurden unmittelbar nach der Behandlung beobachtet. Grad 3/4 Melphalan-assoziierte Panzytopenien entwickelten sich nach 1 – 2 Wochen. Alle hämatologischen Ereignisse wurden effektiv mit Transfusionen und/oder anderen unterstützenden Maßnahmen behandelt. Mit dem neuen, hocheffizienten Filtersystem gab es geringere Nebenwirkungen und eine beschleunigte Erholung. In einem Fall musste das Verfahren aufgrund von einer heparininduzierten vaginalen Blutung vorzeitig abgebrochen werden und ein Patient starb aufgrund retroperitonealer Blutung unter Heparinantikoagulation.

Schlussfolgerung: Chemosaturation-PHP nicht resektabler Lebermetastasen ist eine geeignete Behandlungsoption, die von einem erfahrenen, multidisziplinären Team durchgeführt werden kann. Es scheint ein aussichtsreiches regionales Verfahren für Patienten ohne andere effektive Behandlungsmöglichkeiten zu sein.

Key words

melphalan - liver - metastases - hepatic perfusion - hemofiltration - safety

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