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Der Onkologe

, Volume 25, Issue 2, pp 131–144 | Cite as

Medikamentöse Therapie des Ovarialkarzinoms in der Primär- und Rezidivsituation

  • Frederik MarméEmail author
  • Philipp Harter
  • Beyhan Ataseven
Leitthema
  • 162 Downloads

Zusammenfassung

Hintergrund

Das Verständnis der Heterogenität der Tumorbiologie des Ovarialkarzinoms hat in den letzten 10 Jahren rasant zugenommen. Dies hat neben der Einführung der Antiangiogenese als Therapieprinzip auch zur Definition eines zentralen therapeutischen Ziels geführt. Defekte in der homologen Rekombination sind, basierend auf dem Prinzip der synthetischen Letalität, therapeutisch nutzbar und haben zur Einführung der PARP-Inhibitoren als essenziellem Therapiebaustein geführt.

Material und Methoden

Diese Arbeit basiert auf einer selektiven Literaturrecherche der Datenbank PubMed sowie Abstracts relevanter Kongresse und aktueller nationaler und internationaler Leitlinien.

Ergebnisse

In der letzten Zeit haben sich mit der Antiangiogenese und der Einführung der PARP-Inhibitoren die Behandlungsmöglichkeiten zunehmend diversifiziert. So werden die PARP-Inhibitoren als Erhaltungstherapie den Standard des BRCA-assoziierten Ovarialkarzinoms in der in Zukunft Primärtherapie definieren. Die Kenntnis des BRCA-Status zu Beginn der Primärtherapie ist für eine sinnvolle individuelle Therapieplanung auch im Hinblick auf die Therapiesequenzen unabdingbar. Die streng kalendarisch definierte Einteilung in platinsensitive und -resistente Rezidive wurde verlassen, und die Bedeutung multipler Faktoren für die Entscheidung, ob eine platinhaltige Therapie im Rezidiv sinnvoll erscheint, betont. Die entsprechenden Therapieoptionen werden getrennt nach Primär- und Rezidivtherapie sowie getrennt nach den Therapieprinzipien anhand deren Evidenz diskutiert.

Diskussion

Die Integration effektiver zielgerichteter Therapien hat erstmals zur Wahl zwischen verschiedenen Therapieoptionen geführt. Die klinische Entwicklung über die Antiangiogenese und PARP-Inhibitoren hinaus hat aktuell mit vielen parallelen Phase-III-Studien deutlich Fahrt aufgenommen. Hauptsächlich untersuchen diese die Integration immuntherapeutischer Ansätze in die bestehenden Therapiestrategien.

Schlüsselwörter

Chemotherapie Platin Antiangiogenese BRCA-Mutation PARP-Inhibitor 

Pharmaceutical treatment of ovarian cancer in primary and recurrent situations

Abstract

Background

The understanding of the molecular basis and heterogeneous nature of the tumor biology of ovarian cancer has rapidly increased over the last 10 years. In addition to the introduction of antiangiogenesis as a treatment principle this has also led to the definition of a central treatment target. Defects in homologous recombination are therapeutically usable based on the principle of synthetic lethality and have led to the introduction of PARP inhibitors as an integral component of treatment.

Material and methods

This review is based on a selective literature search of the PubMed database, relevant meeting abstracts and current national as well as international guidelines.

Results

Based on the introduction of PARP inhibitors in addition to antiangiogenic therapies, the treatment options for ovarian cancer have become more refined and diversified. The PARP inhibitors as maintenance treatment define a new standard in the primary treatment of BRCA-mutated advanced ovarian cancer. The BRCA mutation status provides indispensable information for individual treatment selection at the beginning of the first-line therapy also with respect to the sequence of treatment. In addition, the strictly defined classification into platinum sensitivity and resistant recurrences based exclusively on the platinum-free interval was recently abandoned. Instead, the importance of multiple factors that need to be considered in the decision whether a platinum-based treatment would be a good option for an individual patient was emphasized. The respective treatment options and their evidence are discussed separately for the first-line and recurrent settings as well as for the different treatment principles.

Discussion

The integration of effective targeted therapies has for the first time led to different treatment choices in a specific clinical situation. Clinical development in large phase III trials has picked up pace, currently focusing mainly on immunotherapies and their integration into the current treatment strategies including chemotherapy, bevacizumab and PARP inhibitors.

Keywords

Chemotherapy Platinum Angiogenesis BRCA mutation PARP inhibitors 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

F. Marmé: Honorare (Vorträge/Advisory Boards) und Reisekosten: AstraZeneca, Tesaro, Clovis, Roche, Pfizer, Novertis, Amgen, PharmaMar, Genomic Health, CureVac, EISAI, Celgene. P. Harter: Honoraria: AstraZeneca, Roche, Tesaro, Stryker, ASCO, Zai Lab, Advisory Board: AstraZeneca, Roche, Tesaro, Lilly, Clovis, Immunogen Research Funding (Inst): AstraZeneca, Roche, GSK, Böhringer Ingelheim, Medac, DFG, European Union, DKH. B. Ataseven Adboard: Roche, Amgen, Reisekosten/Kongressteilnahme: Roche, Tesaro, Referentenhonorar bei wissenschaftlichen VA: Roche, AstraZeneca.

Alle beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethik-Kommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Von allen beteiligten Patienten liegt eine Einverständniserklärung vor.

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Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  • Frederik Marmé
    • 1
    • 2
    Email author
  • Philipp Harter
    • 3
  • Beyhan Ataseven
    • 3
    • 4
  1. 1.Universitätsfrauenklinik HeidelbergHeidelbergDeutschland
  2. 2.Nationales Centrum für Tumorerkrankungen (NCT)HeidelbergDeutschland
  3. 3.Klinik für Gynäkologie und Gynäkologische OnkologieKliniken Essen MitteEssenDeutschland
  4. 4.Klinik für Gynäkologie und GeburtshilfeLudwig Maximillian UniversitätMünchenDeutschland

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