Adäquate Supportivtherapie im therapeutischen Einsatz von „Biologicals“ bei gastrointestinalen(GI) Tumoren in der Onkochirurgie – Was muss der Chirurg wissen?

Zusammenfassung

Hintergrund: Mit der zunehmenden Anwendung neuartiger antineoplastisch ausgerichteter Substanzen (Inhibitoren, Antikörper [Ak]) entsprechend der Ebenen/Angriffspunkte einer tumorzellspezifischen Signaltransduktionskaskade der Zelle oder von Botenstoffen [„Biologicals“, „targeted therapy“]) ist auch eine neue Qualität, Ausprägung/Intensität und Komplexität von Nebenwirkungen assoziiert, die ebenso für den Onkochirurgen relevant sind.

Ziel: Zusammenfassung klinisch gewonnener Expertise unter Angabe von praxisrelevanten Anwendungs-, Vorgehens- und Verhaltensempfehlungen bei abnormen und Nebenwirkungen sowie toxischen Reaktionen von Biologicals unter Vergleich mit publizistisch verfügbaren Erkenntnissen im systematischen Kurzüberblick der bisher in die klinische Anwendung übergegangenen Substanzen und Präparate bei GI-Tumoren.

Methode: Kompakte Kurzübersicht, basierend auf autorengestützter klinischer Alltagserfahrung inklusive selektiver und vergleichender Literaturrecherche in PubMed (Suchbegriffe: „supportive treatment/therapy“, „biological[s“]).

Ergebnisse: Das dargestellte Profil von Biologicals umfasst: Herceptin^®/Trastuzumab (Her2 neu-AK), Erbitux^®/Cetuximab (EGFR-AK), Glivec^®/Imatinib, Sutent^®/Sunitinib und Nexavar^®/Sorafenib (als Multikinaseinhibitoren) – Querverweis auf hämatologisch-onkologische Literatur für MabThera^®/Rituximab und Sprycel^®/Dasatinib; Tasigna^®/Nilotinib –, die alle mehr oder weniger schwerwiegende, teils einzelne oder kombinierte, bekannte (hämatologische, gastroenterologische, neurologische und dermatologische nach WHO-Klassifikation) und völlig neuartige (GI-Perforation bei Avastin^®; scheinbare Dominanz von neurologischen/dermatologischen Nebeneffekten), aber weitestgehend substanz- bzw. präparate-spezifische Konstellationen auch im Nebenwirkungsspektrum zeigen, die mehrheitlich jedoch durchaus als beherrschbar anzusehen sind. Dieser Umstand erhöht die Anforderungen an die Expertise des heute tätigen versierten Onkologen/Onkochirurgen.

Diskussion: Das Management Biologicals-assoziierter Nebenwirkungen ist ein neuer Aspekt im Gesamtkonzept onkologischer Betreuung, das eine sowohl teils bekannte als auch neue Phänomenologie zeigt und damit adaptierte Therapieansätze erfordert.

Abstract

Background: Along with the increasing use and inauguration of novel antineoplastic substances (inhibitors, antibodies [Ab]) at various levels of the tumour cell-specific intracellular signalling (transduction cascade) on the cell surface and within the cell as well as messengers [“biologicals”, “targeted therapy”]), a new quality, intensity and complexity of adverse effects was simultaneously developed, which have become more and more relevant even to oncosurgeons.

Aim: A summary is given of clinically obtained expertise including recommendations for a competent approach, management and use of biologicals for targeted therapy in case of abnormal or adverse effects as well as toxic reactions, which are compared with available data from the literature and provided as systematic short review on the clinically used substances and drugs in GI tumour lesions.

Methods: The compact overview is based on the authorsʼ daily clinical experiences including a selective and comparative literature search in PubMed (searching strategy using the following terms: “supportive treatment/therapy”, “biological[s]”).

Results: The discussed profile of biologicals comprises: Herceptin^®/Trastuzumab (Her2 neu-AK), Erbitux^®/Cetuximab (EGFR-AK), Glivec^®/Imatinib, Sutent^®/Sunitinib and Nexavar^®/Sorafenib (multikinase inhibitors) – reference to haematological and oncological literature for MabThera^®/Rituximab and Sprycel^®/Dasatinib; Tasigna^®/Nilotinib. All of them induce more or less severe, partially single or combined, known (haematological, gastroenterological, neurological and dermatological [according to the WHO classification]) or completely novel (GI perforation in case of Avastin^®; apparent predominance of neurological and dermatological) adverse effects, which show (in the majority of cases) substance- and/or drug-specific properties in the spectrum of adverse effects, which can be sufficiently managed. These circumstances increase the requirements for the expertise of todayʼs responsible oncologists/oncosurgeons.

Discussion: The management of “biologicals”-associated adverse effects can be considered a novel aspect in the overall concept of oncological care, which shows a partially known as well as novel phenomenology and, thus, requires adapted therapeutic approaches.

Schlüsselwörter

Biologicals - Targeted Therapy - Nebenwirkung - toxische Reaktion - supportive Therapie

Key words

biologicals - targeted therapy - adverse effects - toxic reactions - supporting treatment

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