Zusammenfassung
□Hintergrund: Das Wissen um die Bedeutung, die pathophysiologischen Mechanismen und das Management der Chemotherapie-induzierten Emesis hat in den letzten 20 Jahren exponentiell zugenommen. In den achtziger Jahren wurde die hochdosierte Metoclopramid (MCP)-Therapie eingeführt, in den späten achtziger und frühen neunziger Jahren dann die Therapie mit Serotonin-Typ-3-Rezeptorantagonisten (5-HT3-Antagonisten). Beide Substanzklassen haben zu einer spürbaren Verbesserung der Ergebnisse antiemetischer Therapien beigetragen. Nach 20 Jahren intensiver klinischer Forschung scheint es angebracht, eine Zwischenbilanz zu ziehen.
□Methodik: Mit Hilfe einer Übersicht und Re-Analyse der bis dato publizierten Literatur zu diesem Thema wird der aktuelle Stand der Forschung (inklusive der Felder, in denen weitere Verbesserungen notwendig sind) dargestellt. Dort, wo dieses möglich erscheint, werden Empfehlungen zum aktuellen „Goldstandard“ der antiemetischen Therapie formuliert.
□Ergebnisse und Schlußfolgerungen: Bei allen hoch oder sehr hoch emetogenen Chemotherapien sollte am Therapietag eine antiemetische Prophylaxe eingesetzt werden. Dies gilt vor allem für alle Platin- und die meisten Cyclophosphamid-haltigen Therapien. Die Prophylaxe der Wahl besteht aus der Kombination eines 5-HT3-Antagonisten mit einem Corticosteroid. Gegen das sogenannte verzögerte Erbrechen an den Folgetagen sollten alle Patienten eine orale Corticoid-Therapie, eventuell in Kombination mit MCP (vor allem bei Platin-Therapie), seltener auch mit 5-HT3-Antagonisten erhalten. Mit dieser Prophylaxe können bei der Mehrzahl der Patienten die Emesis vollständig verhindert und die Nausea zumindest reduziert werden. Bei den 5-HT3-Antagonisten reicht eine Einmalgabe vor der Chemotherapie aus. Für Ondansetron und Granisetron, die am besten untersuchten Substanzen aus dieser Klasse, können 8 mg (Ondansetron) und 3 mg (Granisetron) als Standarddosis angesehen werden. Bei den Corticoiden liegen die meisten Daten für Dexamethason vor. Als Standarddosis können 10–20 mg vor der Chemotherapie gegeben werden. Nach der Chemotherapie und besonders an den Folgetagen scheint eine Mehrfachdosierung angezeigt.
□Ausblick: Weitere Verbesserungen der Therapie, insbesondere bezüglich der Emesis und Nausea an den Folgetagen, sind notwendig und derzeit Objekt klinischer Forschung.
Summary
□Background: The knowledge of the importance, the physiopathological mechanisms, and the management of the chemotherapy-induced emesis has increased exponentially during the last 20 years. High-dosage metoclopramide (MCP) therapy has been introduced in the eighties and serotonine type-3 receptor antagonists (5-HT3 antagonists) have been used since the late eighties and early nineties. Due to both classes of substances the results of the antiemetic therapies have improved drastically. After 20 years of intensive clinical research it seems to be appropriate to come to an intermediate conclusion.
□Method: With the aid of an overview and a new analysis of the literature published on this topic so far, the current state of research is shown (including the fields in which further improvement will be necessary), and suggestions are made, wherever it seemed possible, to attain the “gold standard” in antiemetic therapy.
□Results and Conclusions: In connection with all highly or very highly emetogenic chemotherapies, an antiemetic prophylaxis should be initiated on the day of therapy, especially when using platinum or most of the cyclophosphamide-based regimes for cancer treatment. The recommended prophylaxis consists of a combination of 5-HT3 antagonists with a corticosteroid. To combat the so-called delayed emesis on the days following therapy, all patients should undergo an oral corticoid therapy, possibly in combination with MCP (especially platinum-therapy patients), less frequently with 5-HT3 antagonists. With these means of prophylaxis emesis can be prevented/avoided completely in most patients, and nausea can at least be reduced. It is sufficient to administer a single dose of 5-HT3 antagonists prior to chemotherapy. For ondansetron and granisetron, the best documented substances within this class of drugs, 8 mg (ondansteron) and 3 mg (granisetron) are considered standard dosages. Among the corticoids, most data have been accumulated for dexamethasone. A standard dose of 10 to 20 mg can be administered prior to chemotherapy. Right after and especially on the days following chemotherapy higher dosages seem to be indicated.
□Prospect: Further therapy improvements, especially concerning emesis and nausea on the days following chemotherapy, are necessary and are currently object of clinical research.
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Du Bois, A. Management der Chemotherapie-induzierten Emesis: Was ist Standard nach 20 Jahren klinischer Forschung?. Med Klin 93 (Suppl 1), 3–17 (1998). https://doi.org/10.1007/BF03041988
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DOI: https://doi.org/10.1007/BF03041988