Efficacy and safety of AEZS-108 (INN: zoptarelin doxorubicin acetate) an LHRH agonist linked to doxorubicin in women with platinum refractory or resistant ovarian cancer expressing LHRH receptors: a multicenter phase II trial of the ago-study group (AGO GYN 5)

Gynecol Oncol. 2014 Jun;133(3):427-32. doi: 10.1016/j.ygyno.2014.03.576. Epub 2014 Apr 5.


Objectives: To evaluate the activity and toxicity of AEZS-108 (Zoptarelin Doxorubicin Acetate) an LHRH agonist linked to doxorubicin in women with platinum refractory or resistant ovarian cancer expressing LHRH receptors.

Methods: Women with epithelial ovarian, fallopian tube or primary peritoneal cancer, expressing LHRH receptors were eligible for this trial, when they had progression during treatment with a platinum based regimen or within 6months after receiving a platinum based regimen and a previous taxane treatment. At least one measurable target lesion (RECIST) or CA-125 levels higher than twice the upper limit of normal range (GCIG-criteria) were required. Patients received AEZS-108 (267mg/m(2) equimolar to 76.8mg/m(2) of free doxorubicin) every 3weeks as a two hour i.v. infusion.

Results: Fifty-five of 59 (93%) of ovarian cancer samples screened expressed LHRH receptors. 42 patients were enrolled in this study and received at least 1 infusion of AEZS-108 (ITT population). Of these 42 patients 6 (14.3%) had a partial response, 16 (38%) stable disease, 16 (38%) progressive disease and 4 patients were not evaluable. Median time to progression was 12weeks (95% CI: 8-20weeks), and median overall survival was 53weeks (95% CI: 39-73weeks). Toxicity profile was favorable.

Conclusion: AEZS-108 has a clinical activity in platinum refractory/resistant ovarian cancer which seems to be comparable to that of pegylated liposomal doxorubicin or to topotecan. Toxicity was comparably low. These data support the concept of a targeted chemotherapy for tumors expressing LHRH receptors.

Keywords: LHRH receptor targeted; Ovarian cancer; Platinum-refractory; Platinum-resistant; Targeted chemotherapy.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adenocarcinoma, Clear Cell / drug therapy*
  • Adenocarcinoma, Clear Cell / metabolism
  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • CA-125 Antigen / metabolism
  • Cystadenocarcinoma, Serous / drug therapy*
  • Cystadenocarcinoma, Serous / metabolism
  • Disease-Free Survival
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm
  • Fallopian Tube Neoplasms / drug therapy*
  • Fallopian Tube Neoplasms / metabolism
  • Female
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / metabolism
  • Platinum Compounds / therapeutic use
  • Receptors, LHRH / metabolism
  • Taxoids / therapeutic use
  • Treatment Outcome


  • Antineoplastic Agents, Hormonal
  • CA-125 Antigen
  • Platinum Compounds
  • Receptors, LHRH
  • Taxoids
  • LHRH, lysine(6)-doxorubicin
  • Gonadotropin-Releasing Hormone
  • Doxorubicin