Objective: Advanced or recurrent endometrial cancer (EC) no longer amenable to surgery or radiotherapy is a life-threatening disease with limited therapeutic options left. Eighty percent of ECs express receptors for luteinizing hormone–releasing hormone (LHRH), which can be targeted by AEZS-108 (zoptarelin doxorubicin acetate). This phase 2 trial was performed to assess the efficacy and safety of AEZS-108 in this group of patients.
Methods: Patients had FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) III or IV or recurrent EC, LHRH receptor–positive tumor status, and at least had 1 measurable lesion (Response Evaluation Criteria in Solid Tumors). Prior anthracycline therapy was not allowed. Patients received AEZS-108 as a 2-hour infusion on day 1 of a 21-day cycle. The treatment was continued for a maximum of 6 to 8 cycles. The primary end point was the response rate determined by the Response Evaluation Criteria in Solid Tumors.
Results: From April 2008 to November 2009, 44 patients were included in the study at 8 centers in Germany (AGO) and 3 centers in Bulgaria. Forty-three of these patients were eligible. Two (5%) patients had a complete remission, and 8 (18%) achieved a partial remission. Stable disease for at least 6 weeks was observed in 44%. The median time to progression was 7 months, and the median overall survival was 15 months. The most frequently reported grade 3 or 4 adverse effects were neutropenia (12%) and leucopenia (9%).
Conclusions: AEZS-108, an LHRH-agonist coupled to doxorubicin, has significant activity and low toxicity in women with advanced or recurrent LHRH receptor–positive EC, supporting the principle of receptor-mediated targeted chemotherapy.
*Georg-August-Universität Göttingen, Frauenklinik, Göttingen, Germany; †University Hospital “Dr. Georgy Stranski,” Pleven, Bulgaria; ‡Kliniken Essen-Mitte, Evang. Huyssens-Stiftung/Knappschaft Krankenhaus, Klinik für Gynäkologische Onkologie; and §Universitätsklinikum Duisburg-Essen, Universitätsfrauenklinik, Essen; ∥St. Vincentius Kliniken, Klinik für Gynäkologie u. Geburtshilfe, Karlsruhe; ¶Klinikum der J. W. Goethe-Universität, Klinik für Frauenheilkunde u. Geburtshilfe, Frankfurt; #Universitätsklinikum Schleswig-Holstein, Klinik für Gynäkologie u. Geburtshilfe, Kiel; **Universität Erlangen-Nürnberg, Klinik für Frauenheilkunde, Erlangen; ††Klinikum Lüneburg, Frauenklinik, Lüneburg; ‡‡Æterna Zentaris GmbH, Frankfurt; and §§Charité Campus Virchow-Klinikum, Klinik für Frauenheilkunde und Geburtshilfe, Berlin, Germany.
Address correspondence and reprint requests to Günter Emons, MD, PhD, Georg-August-Universität Göttingen, Frauenklinik, Robert-Koch-Str. 40, 37075 Göttingen, Germany. E-mail: email@example.com.
Supported by Æterna Zentaris GmbH, which provided the funding and the study drug.
The authors declare no conflicts of interest.
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Received September 4, 2013
Received in revised form October 18, 2013
Accepted October 18, 2013