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Aktuelle Entwicklungen zur neoadjuvanten und adjuvanten Therapie des Pankreaskarzinoms

Recent developments in neoadjuvant and adjuvant treatment of pancreatic cancer

  • Leitthema
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Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Trotz kurativ intendierter chirurgischer Resektion ist die Prognose des duktalen Pankreasadenokarzinoms (PDAC) aufgrund der aggressiven Tumorbiologie mit hohem Metastasierungspotenzial auch in lokalisierten Tumorstadien weiterhin sehr ungünstig (mediane Fünfjahresüberlebensrate ≤10 %).

Ziel

Die aktuellen systemischen Therapiekonzepte beim lokalisierten, nichtmetastasierten PDAC sollen dargestellt werden.

Material und Methoden

Diese Arbeit basiert auf einer selektiven Literaturrecherche in der Datenbank PubMed und aktueller Kongressabstracts zum Thema adjuvante und neoadjuvante Therapie des PDAC.

Ergebnisse

Seit Einführung und Weiterentwicklung einer effektiven adjuvanten Systemtherapie konnte die Prognose des resektablen PDAC konsekutiv verbessert werden, während adjuvante Radio(chemo)therapiekonzepte keinen klaren Zusatznutzen zeigen. Für selektierte Patientenkollektive (u. a. ECOG 0, Alter <70 Jahre) stellt aktuell die Kombinationstherapie nach dem modifizierten FOLFIRINOX-Schema den neuen Therapiestandard in der Adjuvanz dar. Alle anderen Patienten sollten weiterhin nach chirurgischer Resektion eine adjuvante Gemcitabin- oder 5‑Fluorouracil(5-FU)-basierte Systemtherapie über 6 Monate erhalten. Wegen des limitierten Zugangs zu einer effektiven postoperativen Systemtherapie (nur maximal 50 % aller resezierten Patienten erhalten eine adjuvante Systemtherapie) und des potenziellen Downsizing-Effekts mit Steigerung der R0-Resektabilitätsrate werden derzeit in Studien neoadjuvante Konzepte mit modernen Kombinationschemotherapien (FOLFIRINOX, Gemcitabin/nab-Paclitaxel) in verschiedenen lokalisierten Stadien des PDAC (resektabel, Borderline-resektabel, primär irresektabel) evaluiert. Diese stellen aber noch keinen allgemeinen Therapiestandard dar.

Schlussfolgerung

Eine effektive perioperative Systemtherapie stellt heutzutage einen integralen Bestandteil eines interdisziplinären Behandlungskonzepts lokalisierter PDAC dar.

Abstract

Background

Despite the curative intent of surgical resection, pancreatic ductal adenocarcinoma (PDAC) even in localized stages has a very poor prognosis (5-year median overall survival ≤10%) due to the aggressive tumor biology with a high potential to develop metastatic disease.

Objective

This article presents the current concepts for systemic treatment in localized, non-metastatic PDAC.

Methods

This article is based on a selective literature search in the PubMed database and recent congress abstracts concerning adjuvant and neoadjuvant treatment of PDAC.

Results

With the introduction and further refinement of effective adjuvant systemic chemotherapy, the prognosis of resectable PDAC has been consecutively improved, whereas (chemo)radiotherapy concepts have not shown additional benefits. For selected patient subgroups (e. g. PS-ECOG 0, age <70 years) combination chemotherapy with the modified FOLFIRINOX regimen is considered the current standard treatment in the adjuvant setting. All other patients should receive adjuvant chemotherapy with gemcitabine or a 5-FU-based systemic treatment regimen over 6 months after surgical resection. Due to limited access to effective postoperative systemic treatment (only approximately 50% of resected patients receive an adjuvant chemotherapy) and the potential downsizing effect with an increase in the R0 resection rate, current clinical trials are evaluating neoadjuvant concepts with modern combination chemotherapy regimens (FOLFIRINOX, gemcitabine/nab-paclitaxel) in various localized stages of PDAC (resectable, borderline resectable, primarily nonresectable); however, this is not yet standard treatment outside clinical trials.

Conclusion

An effective perioperative systemic treatment is nowadays an essential part of the multidisciplinary treatment strategy for localized PDAC.

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik II & Comprehensive Cancer Center Mainfranken, Schwerpunkt Medizinische Onkologie, Universitätsklinikum Würzburg, Oberdürrbacherstr. 6–8, 97080, Würzburg, Deutschland

    Volker Kunzmann &  Ingo Hartlapp

  2. Klinik für Innere Medizin I, Universitätsklinikum Ulm, Ulm, Deutschland

    Thomas J. Ettrich &  Thomas Seufferlein

Authors
  1. Volker Kunzmann
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  2. Thomas J. Ettrich
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Correspondence to Volker Kunzmann.

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Interessenkonflikt

V. Kunzmann: Forschungsunterstützung: Celgene; Vortragshonorare: BMS, Celgene, Merck, Servier; Advisory Boards: BMS, Celgene, Merck. T.J. Ettrich: Kongressunterstützung: Ipsen, Forschungsunterstützung: Servier; Vortragshonorare, Advisory Boards: Merck-Serono, Sanofi, Novartis, Bayer, BMS, Sanofi, Roche. T. Seufferlein: Forschungsunterstützung Sanofi-Genzyme, Celgene, Amgen; Vortragshonorare: Celgene, Servier, Merck, Roche, Falk Foundation, Shire, Novartis, Sanofi-Genzyme; Advisory Boards: BMS, Celgene, Halozyme, Lilly, Sanofi-Genzyme. I. Hartlapp: Advisory Boards: Roche

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Kunzmann, V., Ettrich, T.J., Hartlapp, I. et al. Aktuelle Entwicklungen zur neoadjuvanten und adjuvanten Therapie des Pankreaskarzinoms. Onkologe 25, 669–677 (2019). https://doi.org/10.1007/s00761-019-0549-6

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  • DOI: https://doi.org/10.1007/s00761-019-0549-6

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