title: 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).
abstract: 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.
authors.affiliation: *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.
authors.forename: Günter
authors.initials: G
authors.lastname: Emons
authors.forename: Grigor
authors.initials: G
authors.lastname: Gorchev
authors.forename: Philipp
authors.initials: P
authors.lastname: Harter
authors.forename: Pauline
authors.initials: P
authors.lastname: Wimberger
authors.forename: Anne
authors.initials: A
authors.lastname: Stähle
authors.forename: Lars
authors.initials: L
authors.lastname: Hanker
authors.forename: Felix
authors.initials: F
authors.lastname: Hilpert
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Beckmann
authors.forename: Peter
authors.initials: P
authors.lastname: Dall
authors.forename: Carsten
authors.initials: C
authors.lastname: Gründker
authors.forename: Herbert
authors.initials: H
authors.lastname: Sindermann
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D011966:Receptors, LHRH; C080883:LHRH, lysine(6)-doxorubicin; D007987:Gonadotropin-Releasing Hormone; D004317:Doxorubicin