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).
OBJECTIVE
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.


CONCLUSIONS
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.
Georg August Universität, Robert-Koch-Str. 40, 37075 Göttingen, Germany. Electronic address: emons@med.uni-goettingen.de.
Günter
G
Emons
University Hospital "Dr. Gregory Stranski", 20 Sv. Kitil I Metodii Str., Pleven, Bulgaria. Electronic address: rector@mu-pleven.bg.
Grigor
G
Gorchev
Charité, Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address: jalid.sehouli@charite.de.
Jalid
J
Sehouli
Universitätsklinikum Essen, Hufelandstr. 55, 45147 Essen, Germany. Electronic address: pauline.wimberger@uniklinikum-dresden.de.
Pauline
P
Wimberger
St. Vincentius Kliniken Karlsruhe, Edgar-von Gierke-Str. 2, 76135 Karlsruhe, Germany. Electronic address: anne.staehle@web.de.
Anne
A
Stähle
Universitätsklinikum Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. Electronic address: Lars.Hanker@uksh.de.
Lars
L
Hanker
Universitätsklinikum Schleswig-Holstein, Campus Kiel, Brunswiker Str. 10, 24105 Kiel, Germany. Electronic address: fhilpert@email.uni-kiel.de.
Felix
F
Hilpert
AEterna Zentaris GmbH, Wiesmüllerstr. 50, 603414 Frankfurt am Main, Germany. Electronic address: herbert.sindermann@zentaris.com.
Herbert
H
Sindermann
Georg August Universität, Robert-Koch-Str. 40, 37075 Göttingen, Germany. Electronic address: grundker@med.uni-goettingen.de.
Carsten
C
Gründker
Dr. Horst Schmidt Klinik, Ludwig-Erhard-Str. 100, 65199 Wiesbaden, Germany. Electronic address: p.harter@gmx.de.
Philipp
P
Harter
D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D018394:CA-125 Antigen / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000378:metabolism; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017671:Platinum Compounds / Q000627:therapeutic use; D011966:Receptors, LHRH / Q000378:metabolism; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D018394:CA-125 Antigen; D017671:Platinum Compounds; D011966:Receptors, LHRH; D043823:Taxoids; C080883:LHRH, lysine(6)-doxorubicin; D007987:Gonadotropin-Releasing Hormone; D004317:Doxorubicin
LHRH receptor targeted; Ovarian cancer; Platinum-refractory; Platinum-resistant; Targeted chemotherapy