Die transpulmonalarterielle Chemoembolisation – vom Labor zur klinischen Anwendung

Zusammenfassung

Die lokoregionären Ansätze bei inoperablen Lungenmetastasen finden in der Literatur wenig Beachtung. Es liegen zwar ausführliche tierexperimentelle Untersuchungen über Wirksamkeit und fehlende Toxizität der isolierten Lungenperfusion (ILP) vor, allerdings sind klinische Studien begrenzt. Dies liegt wahrscheinlich an der Invasivität und am großen technischen Aufwand der Therapie und dies meist in der palliativen Situation. Erst seit Kurzem wird die Chemoembolisation der Lunge im Tiermodell durchgeführt und mit der isolierten Lungenperfusion und der intravenösen Therapie verglichen. Mit simultaner einseitiger Injektion degradierbarer Stärkemikrosphären und Carboplatin in die Pulmonalarterie wurde eine temporäre reversible Embolisation auf kapillärer und arteriolärer Ebene erreicht. Die Chemoembolisation war der intravenösen Chemotherapie überlegen und zeigte ein ähnliches Ansprechen wie die isolierte Lungenperfusion im solitären Lungenmetastasenmodell. Sie war nicht mit einer Frühtoxizität behaftet, und die Spätauswirkung auf das Lungenparenchym war mit denen der intravenösen Therapie und der isolierten Lungenperfusion vergleichbar. Bei der Chemoembolisation wird nur ein Drittel der üblichen, intravenös verabreichten Zytostatikadosis verwendet, daher sind die allgemeinen Nebenwirkungen nicht limitierend. Im Vergleich zur intravenösen Therapie wurde eine signifikant höhere Zytostatikakonzentration im Tumorgewebe, in den Lymphknoten und im gesunden Lungengewebe erreicht. Im Großtiermodell konnte gezeigt werden, dass diese neue Methode interventionell über einen Pulmonaliskatheter durchführbar ist und nicht zu einer relevanten Veränderung des Kreislaufs führt. Chronische Schäden nach 6 Monaten sind nicht aufgetreten. Erste klinische Anwendungen zeigen demnach die Machbarkeit und die gute Toleranz bei Patienten mit inoperablen Lungenmetastasen.

Abstract

Locoregional approaches for inoperable lung metastases described in the literature are limited to isolated lung perfusion (ILP). A lot of experimental studies show feasibility and good oncological response with low toxicity. However, clinical applications are rare – probably due to the invasiveness of the procedure in a palliative aim. Recently chemoembolisation of the lung in a small-animal model was performed and compared to isolated lung perfusion and intravenous therapy. Using a simultaneous unilateral injection of degradable starch microspheres and carboplatin into the pulmonary artery, temporary reversible embolization at the capillary and arteriolar level has been achieved. Chemoembolization was superior to intravenous chemotherapy and had a response comparable to that of isolated lung perfusion in the solitary lung metastasis model. It was not associated with early toxicity and the long-term effect on lung parenchyma was similar to those of intravenous therapy and isolated lung perfusion. Since only a third of the normal intravenous cytostatic dose is used in chemoembolization, the general side effects are thus not a limiting factor. In the large-animal model, the new method can be performed interventionally via a pulmonary catheter without changing the circulation relevantly. After 6 months no chronic injury was seen. First clinical applications show that the procedure was well tolerated in patients with unresectable metastases.

Schlüsselwörter

Chemoembolisation - Lungenmetastasen - palliative Therapie - pulmonalarterielle Chemoembolisation

Key words

chemoembolization - lung metastases - palliative treatment - transpulmonary chemoembolization

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