Zusammenfassung
In den vergangenen Jahren haben sich dramatische Neuerungen im Verständnis und der Behandlung solider Tumoren vollzogen. Basierend auf der Tumorbiologie wurden zielgerichtete Therapeutika entwickelt, die direkten Einfluss auf zugrunde liegende genetische und immunologische Veränderungen nehmen. Signifikante Verbesserungen des Überlebens sind der funktionelle Beweis der Wirksamkeit zielgerichteter und immunologischer Tumortherapien. Das Management und die Adhärenz des Patienten sowie die optimierte Kooperation mit den Klinikern sind entscheidend für das Therapieergebnis und die Kontrolle der Erkrankung.
An mehreren soliden Tumoren werden in aktuellen Studien (sequenzielle) Therapien mit zielgerichteten und immunologisch wirksamen Stoffen getestet, z. B. mit Tyrosinkinase- oder mTOR-Inhibitoren, zielgerichteten Antikörpern wie Bevacizumab, spezifischen Antagonisten wie Enzalutamid, und immunologischen Checkpoint-Inhibitoren wie PD-(L)1- und/oder CTLA-4-Antikörpern.
Die aktuell zugelassenen Wirkstoffe haben die Therapieoptionen insbesondere bei folgenden Tumoren erweitert: Prostatakarzinom (Hormontherapie mit Enzalutamid/Abirateronacetat, Radiotherapie mit Radium-223, Cabazitaxel), metastasiertes Mammakarzinom (Eribulin, Everolimus), Nierenzellkarzinom (Sunitinib, Sorafenib, Axitinib, Everolimus, Temsirolimus), nichtkleinzelliges Bronchialkarzinom (Crizotinib, Afatinib), kolorektales Karzinom und gastrointestinaler Stromatumor (Regorafenib) sowie Melanom (Ipilimumab, Vemurafenib). In die Behandlung von selteneren Tumorerkrankungen wie Pankreaskarzinomen, hepatozellulären Karzinomen und Weichteilsarkomen hält die zielgerichtete Therapie mit der Zulassung von nab-Paclitaxel, Sorafenib und Pazopanib Einzug. In aktuellen klinischen Studien werden die optimalen Therapiezeitpunkte und -sequenzen bestimmt und das Management dieser vielversprechenden Wirkstoffe wird verbessert.
Abstract
Recent years have seen dramatic changes in the biological understanding and treatment of solid tumors. Based on the tumor biology, targeting agents have been developed which directly affect the underlying genetic or immunological changes found in specific tumor entities. Significant increases in survival have delivered the functional proof of the concept of targeted and immunological tumor therapy. The management and adherence of the patient as well as optimized cooperation with clinicians are decisive for the results of therapy and disease control.
Several solid tumors are currently under investigation in clinical studies evaluating the (sequential) therapy with targeting and immunologically active agents, e.g. tyrosine kinase and mTOR inhibitors, targeting antibodies, such as bevacizumab, specific antagonists, such as enzalutamide and immunological checkpoint inhibitors via PD(L)1 and/or CTLA 4 antibodies.
Currently approved agents have dramatically changed the landscape of treatment options especially for prostate cancer. Such agents include hormone therapy with enzalutamide and abiraterone, radiotherapy with cabazitaxel and xofigo (radium 223), metastatic breast cancer (eribulin and everolimus), renal cell carcinoma (sunitinib, sorafenib, axitinib, everolimus and temsirolimus), non-small cell lung cancer (crizotinib and afatinib), colorectal cancer and gastrointestinal stromal tumor (regorafenib) and melanoma (ipilimumab and vemurafenib). The treatment of rarer tumors, such as pancreatic and hepatocellular cancer and soft tissue sarcoma has entered the stage of targeted therapy with the approval of nanoparticle albumin-bound (nab)-paclitaxel, sorafenib, and eribulin/pazopanib. Current clinical trials are focusing on the best time point and sequence of therapy and also improvement in the management of these promising agents.
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Einhaltung ethischer Richtlinien
Interessenkonflikt. M. Rickmann wurde von der Firma Bayer durch die Übernahme von Reisekosten unterstützt. V. Grünwald gibt an, dass kein Interessenkonflikt besteht. V. Grünwald: Honorar: GSK, Novartis, Merck Serono, Bayer, Boehringer Ingelheim, Pfizer, Astellas, BMS. Beratertätigkeit: GSK, Novartis, Merck Serono, Pfizer, Astellas, Mologen. Reisekosten: Merck Serono, Novartis, Pfizer, Bayer. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.
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Grünwald, V., Rickmann, M. Arzneitherapie solider Tumoren. Internist 55, 1220–1227 (2014). https://doi.org/10.1007/s00108-014-3553-3
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DOI: https://doi.org/10.1007/s00108-014-3553-3