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ErbB2: Zielstruktur für die Therapie beim Magenkarzinom

ErbB2: a therapeutic target in gastric cancer

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Der Gastroenterologe Aims and scope

Zusammenfassung

Trotz einer effektiven Chemotherapie mit modernen Chemotherapiekombinationen ist die Mortalität beim fortgeschrittenen Magenkarzinom hoch. Es besteht ein großer Bedarf an neuen Therapien. An Magenkarzinommodellen konnte in vivo und in vitro gezeigt werden, dass der gegen HER2 gerichtete monoklonale Antikörper Trastuzumab in der Monotherapie und in der Kombinationschemotherapie das Tumorwachstum hemmen kann. In klinischen Phase-II-Studien zeigte sich durch die Kombination von Trastuzumab und Cisplatin ein Ansprechen bei guter Verträglichkeit. In der randomisierten Phase-III-ToGA-Studie mit Patienten, die an einem HER2-exprimierenden Adenokarzinom des Magens oder des gastroösophagealen Übergangs litten, wurde die Kombinationschemotherapie mit 5-FU oder Capecitabin und Cisplatin plus/minus Trastuzumab verglichen. Es zeigte sich ein Überlebensvorteil für selektierte Patienten, die Trastuzumab zusätzlich erhalten hatten. Aufgrund der Studienergebnisse wurde daraufhin Trastuzumab als erstes Medikament gegen die Zielstruktur HER2 beim Magenkarzinom zugelassen.

Abstract

Most patients with gastric cancer present at an inoperable advanced stage. Although there is a proven benefit for chemotherapy in advanced gastric cancer, mortality remains high and new forms of treatment with acceptable toxicity are needed. Trastuzumab, a monoclonal antibody against HER2, monotherapy and in combination with chemotherapy showed antitumor activity in human gastric cancer models in vitro and in vivo. In clinical phase II trials the combination of trastuzumab and cisplatin showed a reponse with good tolerance. The phase III ToGA trial compared randomized combination chemotherapy protocols with fluorouracil or capecitabine and cisplatin plus or minus trastuzumab in patients with an adenocarcinoma of the gastric or gastro-oesophageal junction expressing HER2. The trial showed a benefit in overall survival in selected patients for the addition of trastuzumab to chemotherapy. The trial led to the approval of trastuzumab by the European Medicines Agency (EMA). Trastuzumab is the first approved biological agent targeting HER2 in gastric cancer.

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  1. II. Medizinische Klinik, Universitätsklinikum Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Deutschland

    S. Belle & M.P. Ebert

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  1. S. Belle
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  2. M.P. Ebert
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Correspondence to S. Belle.

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Belle, S., Ebert, M. ErbB2: Zielstruktur für die Therapie beim Magenkarzinom. Gastroenterologe 7, 8–13 (2012). https://doi.org/10.1007/s11377-011-0611-4

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