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Systemtherapie prognostisch ungünstiger CUP-Syndrome

Adeno- und undifferenzierte Karzinome

Systemic therapy of prognostically unfavorable CUP syndrome

Adeno- and undifferentiated carcinoma

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Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Beim CUP-Syndrom („cancer of unknown primary“) handelt es sich um eine Tumorerkrankung, bei der eine Metastasierung klinisch und histologisch gesichert ist, aber trotz ausführlicher Diagnostik kein Primärtumor nachgewiesen werden kann. CUP-Syndrome machen etwa 2–3 % aller soliden Tumorerkrankungen aus. In den meisten Fällen zeigt sich histologisch ein Adenokarzinom oder ein undifferenziertes Karzinom.

Ergebnisse

An einem CUP-Syndrom erkrankte Patienten, die nicht lokal mit Operation oder Strahlentherapie behandelt werden können und deren Erkrankung nicht einer der definierten günstigen Untergruppen zuzuordnen ist, werden typsicherweise mit einer empirischen Chemotherapie behandelt, auch wenn die Evidenz hierfür aus klinischen Studien aufgrund der Heterogenität und Seltenheit des CUP-Syndroms begrenzt ist. Dabei scheint die Kombination eines der Platinpräparate Carboplatin oder Cisplatin mit einem Taxan wie Paclitaxel am effektivsten zu sein. Alternativ kommt auch eine Behandlung mit einem Platinpräparat zusammen mit Gemcitabin in Betracht. Dreifachkombinationen scheinen keine relevante Verbesserung der Prognose zu erreichen. Noch ist unklar, ob das Ansprechen auf die Chemotherapie durch die Hinzunahme eines Antikörpers verbessert werden kann. Zu dieser Fragestellung werden aktuell die Ergebnisse der deutschen PACET-CUP-Studie erwartet, die randomisiert die Hinzunahme des Antikörpers Cetuximab zu einer Chemotherapie mit Carboplatin und Paclitaxel untersucht. Da die Prognose dieser Patienten trotz empirischer Chemotherapie enttäuschend ist und die meisten Patienten binnen 2 Jahren versterben, werden große Hoffnungen in neue Substanzen gesetzt, die nach einer Mutationsanalyse des Tumorgewebes zielgerichtet eingesetzt werden können. Ein entsprechendes Studienkonzept wird aktuell erarbeitet.

Schlussfolgerung

Disseminierte CUP-Syndrome werden chemotherapeutisch behandelt. Dabei werden typischerweise Kombinationstherapien eines Platinpräparats mit Paclitaxel oder Gemcitabin eingesetzt. Zunehmend kommen auch zielgerichtete Substanzen auf der Grundlage von Mutationsanalysen des Tumorgewebes zum Einsatz.

Abstract

Background

Cancer of unknown primary (CUP) designates cancer with histologically confirmed metastases but without an identifiable primary site in spite of a thorough diagnostic work-up. Approximately 2–3% of all cancers fall into the CUP category. Histologically, adenocarcinomas and undifferentiated carcinomas are the prevailing entities.

Results

Patients with CUP who do not fall into one of the well-defined favorable subsets and who are not eligible for local treatment by surgery or radiotherapy should be treated with empirical chemotherapy, even though evidence from clinical trials is scarce for this rare and heterogeneous entity. A combination chemotherapy with a platinum derivative, either carboplatin or cisplatin and a taxane appears to be the most effective. The combination of a platinum compound together with gemcitabine appears to be an alternative choice. Chemotherapy triplets confer excess toxicity without relevant benefits. Currently, it is unclear whether the addition of an antibody to chemotherapy can improve the prognosis. The results of the German PACET-CUP trial, which is testing the addition of the antibody cetuximab to chemotherapy with carboplatin and paclitaxel in a randomized design, are eagerly awaited. Since chemotherapy fails to overcome the typically dismal prognosis of CUP patients with a median overall survival of less than 2 years, novel therapeutic approaches are warranted. High hopes are placed on mutational profiling and subsequent targeted therapy. A comprehensive study based on molecular profiling and molecularly stratified treatment is currently being prepared.

Conclusion

Disseminated CUP syndromes are commonly treated with chemotherapy. Combination chemotherapies including a platinum compound and either a taxane or gemcitabine are well established. Targeted therapies based on mutational profiling of the tumor tissue are increasingly being introduced into clinical practice.

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Authors and Affiliations

  1. Klinische Kooperationseinheit Molekulare Hämatologie/Onkologie, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Deutschland

    Tilmann Bochtler &  Alwin Krämer

  2. Medizinische Klinik V, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 280, 69120, Heidelberg, Deutschland

    Tilmann Bochtler &  Alwin Krämer

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  1. Tilmann Bochtler
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  2. Alwin Krämer
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Correspondence to Alwin Krämer.

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Interessenkonflikt

T. Bochtler gibt an, dass kein Interessenkonflikt besteht. A. Krämer erhält Unterstützung durch die Firma Merck für die klinische CUP-Studie.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Bochtler, T., Krämer, A. Systemtherapie prognostisch ungünstiger CUP-Syndrome. Onkologe 23, 1000–1005 (2017). https://doi.org/10.1007/s00761-017-0206-x

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  • DOI: https://doi.org/10.1007/s00761-017-0206-x

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