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Prognose, Staging Und Therapie Des Malignen Pleuramesothelioms

W. Neumeister, A. Gillissen, K. Rasche, A. Theile, K. Müller, G. Schultze-Werninghaus
Published 2002 · Medicine

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ZusammenfassungPrognose: Die Prognose des Pleuramesothelioms bleibt unverändert schlecht. Die mittlere Überlebenszeit beträgt zwischen 6 und 12 Monate, das 1-Jahres Überleben liegt bei 20%. Erst 1996 konnte ein allgemein akzeptiertes Staging-System etabliert werden, das an prognostischen Faktoren validiert wurde. Eine effektive Standardtherapie konnte bisher jedoch nicht etabliert werden. Auch sehr agressive Therapieschemata vermochten den natürlichen Verlauf der Erkrankung nicht wesentlich zu beeinflussen. Therapiestudien: Trotz zahlreicher Studien zur Chemotherapie konnte bisher weder für Mono- noch für Polychemotherapien ein Standardregime definiert werden. Nur wenige Substanzen erreichen reproduzierbar Ansprechraten von über 20%, wie sie für den Wirkungsnachweis seltener Tumoren gefordert werden. Die Mehrzahl der Studien ist nach statistischen Kriterien nicht schlüssig. Systematische Erhebungen zur Lebensqualität der häufig sehr toxischen Schemata wurden nur in wenigen Studien durchgeführt. Medikamentöse Therapie: Sowohl die systemische Applikation von Interferon allein als auch in Kombination mit Chemotherapeutika resultiert nicht in höheren Ansprechraten oder einem verlängerten Gesamtüberleben. Sehr frühe Krankheitsstadien profitieren von einer lokalen Applikation von γ-Interferon. Multimodale Therapieansätze: Ausschließlich chirurgische Therapieansätze wie die extrapleurale Pneumektomie oder die Pleurektomie/Dekortikation sind in jüngerer Zeit zugunsten multimodaler Therapieansätze verlassen worden. Durch sorgfältige Patientenauswahl und Verbesserung der Operationstechniken konnte die Mortalität deutlich gesenkt werden. Die Prognose wird jedoch durch das Auftreten von Lokalrezidiven begrenzt, die bisher durch kein adjuvantes Verfahren wie Chemotherapie, Strahlentherapie oder photodynamische Therapie verhindert werden können. Strahlentherapie: Die Wirksamkeit der primären Strahlentherapie bleibt weiterhin umstritten. Eine Kontrolle des Tumorwachstums ist selbst unter Inkaufnahme schwerwiegender Nebenwirkungen nicht gesichert. Unter palliativem Therapieansatz konnte eine Verbesserung tumorassoziierter Symptome nicht nachgewiesen werden. Bisher ist lediglich die Effektivität der prophylaktischen Bestrahlung von Stichkanälen und Thorakotomienarben gesichert. Perspektive: Erkenntnisse der Genforschung konnten in ersten Phase-I-Studien umgesetzt werden. Erst dann, wenn die wenigen vielversprechenden Therapieansätze in randomisierten Phase-II-/Phase-III-Studien mit ausreichend großen Patientenzahlen getestet werden, besteht Hoffnung auf eine wirkungsvolle Standardtherapie.AbstractPrognosis: Prognosis of pleural mesothelioma remains dismal. Regardless of the modality employed median survival ranges between 6 and 12 months, only 20% of patients survive 1 year. In 1996 the International Mesothelioma Interest Group (IMIG) published a widely accepted staging system. So far there is no effective standard therapy. Even very aggressive therapies do not basically influence the course of the disease. Therapeutical Studies: Despite numerous single-agent and combination chemotherapy trials no standard regimen could be found. Few agents yield reproducible response rates above 20%. The majority of the trials are inconclusive according to statistical criteria, as subject numbers are insufficient to prove or deny effectiveness. It also remains obscure in which stage of the disease patients may benefit from chemotherapy because of a lack of analysis of response rates within different stages. Striking is the lack of sufficient studies analyzing patients' quality of life treated with often very toxic regimens. Drug Treatment: Systemic administration of interferons alone or in combination with chemotherapeutic agents did not result in higher response rates or prolonged median survival. In very early stages of the disease patients may have limited benefit from intracavitary, local administration of γ-interferon. Multimodality Approaches: Mere surgical procedures as extrapleural pneumonectomy or pleurectomy/decortication have been left in favor of multimodality approaches. Due to careful patient selection and improved operation techniques mortality could be reduced. Neither chemotherapy, radiotherapy nor photodynamic therapy can prevent local relapse which occurs in the majority of patients. Radiotherapy: The effectiveness of primary radiation therapy remains controversial. Even very high doses of radiation cannot control tumor growth. It remains unclear whether radiation therapy may palliate tumor associated symptoms. Prophylactic radiation of puncture channels and thoracotomy scars is effective to prevent tumor growth caused by seeding of mesothelioma cells. Perspectives: Research of the biological behavior of mesothelioma resulted in first phase I gene therapy trials. The results of the few promising approaches tested in phase II and III trials with sufficient patient numbers have to be awaited until we have learned whether and in which stage of the disease patients may benefit from therapy.
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