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Pneumologie 2014; 68(05): 329-335
DOI: 10.1055/s-0034-1365025
Serie: Pleuramesotheliom
© Georg Thieme Verlag KG Stuttgart · New York

Neue Aspekte der medikamentösen Therapie des malignen Pleuramesothelioms

Malignant Pleural Mesothelioma: New Aspects of Medical Therapy
S. Kurz
Ev. Lungenklinik Berlin, Klinik für Pneumologie
,
C. Grohé
Ev. Lungenklinik Berlin, Klinik für Pneumologie
› Author Affiliations
Subject Editor: C. Grohé, Berlin
Further Information

Publication History

Publication Date:
10 March 2014 (online)

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Zusammenfassung

Das maligne Pleuramesotheliom, in den meisten Fällen durch Asbestexposition verursacht, ist schwer zu behandeln. Für die Therapie der frühen Tumorstadien stehen trimodale Konzepte inklusive Resektion, Radiatio und Chemotherapie im Vordergrund. Für die Erstlinientherapie des fortgeschrittenen MPM ist die Kombination aus Cisplatin und Pemetrexed zugelassen. Allerdings mangelt es an randomisierten kontrollierten Studien zur medikamentösen Zweitlinienbehandlung. Eine Monotherapie mit Pemetrexed, Vinorelbin oder Gemcitabin scheint im Vergleich zu einer rein symptomatischen Behandlung einen Überlebensvorteil zu bringen. Vielversprechend erscheint ein immuntherapeutischer Ansatz. Das Prinzip der „frustranen Phagozytose“, bei der eine kontinuierliche Antigenexposition zu anhaltenden lokalen Entzündungsreaktionen und Antigentoleranz führt, kann durch eine Blockade des T-Zell-Oberflächenproteins CTLA-4 unterbrochen werden. Die Antikörper Ipilimumab und Tremelimumab können so die Immunantwort restimulieren und zu einem Anstieg der Zahl an tumorinfiltrierenden T-Lymphozyten führen. Klinische Studien zu diesem Thema werden mit Spannung erwartet.

Abstract

Malignant pleural mesothelioma, a typical long-term consequence of exposure to asbestos, represents a therapeutic challenge. In the early stages of the disease, trimodal therapy combining surgery, radiation and chemotherapy is used as standard care. In advanced stages, the combination of cisplatin and pemetrexed has been approved as first-line therapy, but there is a lack of randomised controlled drug trials for second-line treatment.

Monotherapy with pemetrexed, vinorelbine or gemcitabine may provide some survival benefit compared to treatment aiming at symptom control only. Immunotherapy seems to be a promising new concept.

The so-called frustrated phagocytosis, with continuing antigen presentation leading to persisting local inflammation and antigen tolerance, can be interrupted by blocking the T-cell surface protein CTLA-4. The monoclonal antibodies ipilimumab and tremelimumab that block CTLA-4 can stimulate immune response and thus increase the number of tumor-infiltrating lymphocytes. Clinical studies exploring this avenue of treatment are being awaited with great excitement.

 

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