TY - JOUR
T1 - Dose escalation and pharmacokinetic study of AEZS-108 (AN-152), an LHRH agonist linked to doxorubicin, in women with LHRH receptor-positive tumors
AU - Emons, Günter
AU - Kaufmann, Manfred
AU - Gorchev, Grigor
AU - Tsekova, Valentina
AU - Gründker, Carsten
AU - Günthert, Andreas R.
AU - Hanker, Lars C.
AU - Velikova, Maya
AU - Sindermann, Herbert
AU - Engel, Jürgen
AU - Schally, Andrew V.
N1 - Funding Information:
This study was funded by Æterna Zentaris GmbH, Frankfurt am Main, Germany .
PY - 2010/12
Y1 - 2010/12
N2 - Objectives: Receptors for luteinizing hormone-releasing hormone (LHRH) can be utilized for targeted chemotherapy of cytotoxic LHRH analogs. The compound AEZS-108 (previously AN-152) consists of [D-Lys6]LHRH linked to doxorubicin. The objectives of this first study in humans with AESZ-108 were to determine the maximum tolerated dose and to characterize the dose-limiting toxicity, pharmacokinetics, preliminary efficacy, and hormonal effects. Methods: The study included 17 women with histologically confirmed epithelial cancer of the ovary, endometrium, or breast that was metastatic or unresectable and for which standard curative or palliative measures could not be used or were no longer effective or tolerated. In each patient, immunohistochemistry of primary tumor or metastatic lesion confirmed that the tumors expressed LHRH receptors. Results: One patient each received intravenous doses of 10, 20, 40, or 80 mg/m2 of AEZS-108, six received 160 mg/m2 and seven 267 mg/m2 at 3 week intervals. Dose-limiting leukopenia and neutropenia were observed at the highest dose. A total of 6 patients, 3 patients each in both upper dose groups, showed responses to AEZS-108. The half-life of AESZ-108 was estimated to be about 2 h. Conclusions: The maximum tolerated dose of AESZ-108 in the absence of supportive medication is 267 mg/m2 and this dose is recommended as starting dose for therapeutic Phase II studies.
AB - Objectives: Receptors for luteinizing hormone-releasing hormone (LHRH) can be utilized for targeted chemotherapy of cytotoxic LHRH analogs. The compound AEZS-108 (previously AN-152) consists of [D-Lys6]LHRH linked to doxorubicin. The objectives of this first study in humans with AESZ-108 were to determine the maximum tolerated dose and to characterize the dose-limiting toxicity, pharmacokinetics, preliminary efficacy, and hormonal effects. Methods: The study included 17 women with histologically confirmed epithelial cancer of the ovary, endometrium, or breast that was metastatic or unresectable and for which standard curative or palliative measures could not be used or were no longer effective or tolerated. In each patient, immunohistochemistry of primary tumor or metastatic lesion confirmed that the tumors expressed LHRH receptors. Results: One patient each received intravenous doses of 10, 20, 40, or 80 mg/m2 of AEZS-108, six received 160 mg/m2 and seven 267 mg/m2 at 3 week intervals. Dose-limiting leukopenia and neutropenia were observed at the highest dose. A total of 6 patients, 3 patients each in both upper dose groups, showed responses to AEZS-108. The half-life of AESZ-108 was estimated to be about 2 h. Conclusions: The maximum tolerated dose of AESZ-108 in the absence of supportive medication is 267 mg/m2 and this dose is recommended as starting dose for therapeutic Phase II studies.
UR - http://www.scopus.com/inward/record.url?scp=78149359898&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2010.08.003
DO - 10.1016/j.ygyno.2010.08.003
M3 - Journal articles
C2 - 20828803
AN - SCOPUS:78149359898
VL - 119
SP - 457
EP - 461
JO - Gynecologic Oncology
JF - Gynecologic Oncology
SN - 0090-8258
IS - 3
ER -
