GENARI - Ein Studienkonzept zur Prüfung von Verträglichkeit, Wirksamkeit und Nutzen einer chemoendokrinen präoperativen Behandlung mit Exemestan

Zusammenfassung

Als Hauptvorteile einer präoperativen Chemotherapie des primären Mammakarzinoms gelten heute die Volumenreduktion des Tumors („Downstaging“) und die Gewinnung zusätzlicher Informationen bezüglich des Ansprechverhaltens des Tumors auf verschiedene Chemotherapeutika („In-vivo-Chemosensitivität“). Damit soll vor allem die Chance für die Durchführung einer brusterhaltenden Operation erhöht werden, ein Wunsch der insbesondere bei jungen Patientinnen im Vordergrund steht. Zudem erlaubt eine solche Therapiestrategie eine gezielte und individualisierte postoperative Behandlung. Verschiedene Studien, in denen die Vorteile präoperativ verabreichter Chemotherapien mit postoperativen Therapien verglichen wurden, lieferten diesbezüglich viele ermutigende Ergebnisse. Demgegenüber sind präoperative Hormontherapien einer Polychemotherapie hinsichtlich des Ansprechens unterlegen. Sie werden in Expertenkreisen deshalb eher kritisch gesehen. Nach Auffassung der Autoren ist dies jedoch nur teilweise gerechtfertigt, da die in den Studien behandelten Patientenkollektive so unterschiedlich sind, dass ein Vergleich beider Therapieformen schwierig erscheint. Um die Möglichkeiten einer präoperativen Behandlung mit Exemestan genauer auszuloten, ist die Studieninitiative GENARI (German Neoadjuvant Aromasin Initiative) ins Leben gerufen worden. Zielsetzung von GENARI ist es zunächst zu prüfen, inwieweit eine präoperative Behandlung mit Exemestan durch gleichzeitige wöchentliche Gabe von Epirubicin oder Docetaxel/Paclitaxel zu verbessern ist. Sollten sich die Kombinationstherapien als wirksam und verträglich erweisen, wird die wirksamste und am besten verträgliche Kombination in einer Folgestudie mit einer präoperativen Standardtherapie verglichen.

Abstract

Preoperative chemotherapy of primary breast cancer is mainly aimed at the reduction of tumor volume and size, a goal that is frequently referred to as downstaging of the tumor and in vivo chemosensitivity testing. While increasing the chance of breast conserving surgery, a therapeutic goal of foremost importance especially for younger women, the tumor response observed after preoperative chemotherapy provides critical information for a more individualized postoperative treatment. These advantages are based on the findings from various studies that investigated the potential benefits of preoperative treatment and compared them to the advantages of conventional postoperative treatment. Given the superiority of preoperative polychemotherapy compared to endocrine treatment the acceptance of the latter is normally poor. The authors, however, believe that direct comparison between cytotoxic and hormonal preoperative treatment irrespective of the differences between the studies is obsolete. Thus in order to further explore the potential of preoperative exemestane, the German Neoadjuvant Aromasin Initiative (GENARI) has been launched. GENARI first of all focuses on the question to what extent the efficacy of preoperative exemestane can be improved by simultaneous administration of weekly epirubicin and docetaxel/paclitaxel. Provided that this approach turns out to be significantly more effective than preoperative monotherapy with exemestane, the most effective and also best tolerated combination will subsequently be compared to a standard preoperative chemotherapy.

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