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Efficacy and Safety of AEZS-108 (LHRH Agonist Linked to Doxorubicin) in Women With Advanced or Recurrent Endometrial Cancer Expressing LHRH Receptors: A Multicenter Phase 2 Trial (AGO-GYN5)

Emons, Günter MD, PhD*; Gorchev, Grigor MD; Harter, Philipp MD; Wimberger, Pauline MD, PhD§; Stähle, Anne MD; Hanker, Lars MD; Hilpert, Felix MD, PhD#; Beckmann, Matthias W. MD, PhD**; Dall, Peter MD, PhD††; Gründker, Carsten PhD*; Sindermann, Herbert PhD‡‡; Sehouli, Jalid MD, PhD§§

International Journal of Gynecological Cancer: February 2014 - Volume 24 - Issue 2 - p 260–265
doi: 10.1097/IGC.0000000000000044
Uterine Cancer

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:

Supported by Æterna Zentaris GmbH, which provided the funding and the study drug.

The authors declare no conflicts of interest.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Received September 4, 2013

Received in revised form October 18, 2013

Accepted October 18, 2013

© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.