A Literature Review-Based Clinical Guide on the Use of Erythropoiesis-Stimulating Agents (ESA) in the Treatment of Patients with Gynaecological Malignancies and Related Anaemia

 

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Zusammenfassung

Fragestellung: Erythropoesestimulierende Substanzen (ESA) werden häufig bei Patienten mit chemotherapieinduzierter Anämie eingesetzt. Sie können den Hämoglobin-(Hb-)Wert korrigieren, den Bedarf von Bluttransfusionen reduzieren, sowie Fatigue und die Lebensqualität verbessern. Besonders relevant ist die Reduktion von Bluttransfusionen durch ESA, da Transfusionen mit erhöhter Mortalität vergesellschaftet sind. Obwohl von zahlreichen Vorteilen durch die Anwendung von ESA berichtet wurde, wird deren Anwendung dennoch kontrovers diskutiert. Neun klinische Studien mit Karzinomen der Brust, Zervix, des Hals- und Kopfbereichs, dem nicht kleinzelligen Bronchialkarzinom, und nicht myeloischen Malignomen haben einen negativen Einfluss von ESA auf das Überleben berichtet. Analysen dieser Studien haben jedoch ergeben, dass die Anwendung der ESA nicht entsprechend den Empfehlungen in Leitlinien und den zugelassenen Indikationen erfolgt ist (höhere ESA-Dosen als empfohlen; ESA-Behandlung nicht anämischer Patienten; Ziel-Hb oberhalb dem empfohlenen Wert von 12 g/dl; Radiotherapie ohne gleichzeitige Chemotherapie; keine tumorspezifische Therapie). Die breite Verwendung von ESA im nicht zugelassenen Bereich dürfte die wahrscheinlichste Ursache für den beobachteten negativen Effekt in den 9 oben erwähnten Studien sein. Zwei große Metaanalysen wurden in den letzten Jahren publiziert (Bennet 2008 [22] und Bohlius 2009 [23]). Von Bedeutung sind insbesondere Subgruppenanalysen, die eindeutig gezeigt haben, dass bei Patientinnen, die zusätzlich zur Gabe von ESA eine Chemotherapie erhalten hatten, keine erhöhte Mortalität in der ESA-Gruppe nachgewiesen werden konnte (HR 1,09 und HR 1,10; nicht signifikanter Unterschied). Schlussfolgerung: ESA sollten nur bei symptomatischen Patientinnen mit einem Hb-Wert < 10 g/dl während Chemotherapie angewendet werden. Der Zielbereich für Hämoglobin sollte nicht über 12 g/dl hinausgehen. In diesen Fällen ist keine erhöhte Mortalität zu erwarten. Dennoch muss bei Behandlung mit ESAs ein signifikant erhöhtes Risiko für die Entwicklung von venösen Thromboembolien einkalkuliert werden.

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For the AGO/OEGGG: Univ. Prof. Dr. Edgar Petru

Univ. Klinik für Frauenheilkunde und Geburtshilfe

Auenbruggerplatz 14

8036 Graz

Österreich

Email: edgar.petru@medunigraz.at