Zoptarelin Doxorubicin
A peptide hormone used to carry chemotherapy into cancer cells
Zoptarelin doxorubicin (AEZS-108, formerly AN-152) joins the chemotherapy drug doxorubicin to [D-Lys6]LHRH, a version of the hormone that controls the reproductive axis. Because many endometrial, ovarian, prostate and breast cancers carry LHRH receptors, the idea was to steer doxorubicin into tumour cells. Phase 2 trials showed responses with modest toxicity, but in a 511-patient phase 3 it was not better than doxorubicin alone.
What is it?
Targeted chemotherapy tries to send a toxic drug only where it is needed. Zoptarelin doxorubicin, first called AN-152 and then AEZS-108, links doxorubicin to an LHRH analogue so that cells carrying LHRH receptors take it up. The endometrial trial's report notes that 80% of endometrial cancers express the receptor, and in the ovarian trial 93% of screened tumours did.
The first human study set the dose in 17 women with ovarian, endometrial or breast cancer. Phase 2 trials followed. In 43 women with advanced or recurrent receptor-positive endometrial cancer, 23% responded (5% complete) and 44% had stable disease, with median overall survival of 15 months. In 42 women with platinum-resistant ovarian cancer, 14.3% had partial responses and median survival was 53 weeks, which the authors judged comparable to standard options. In 25 men with castration- and taxane-resistant prostate cancer, 52% were free of progression at 12 weeks.
The decisive test was a phase 3 trial of second-line therapy for endometrial cancer, which enrolled 511 patients and compared the conjugate with free doxorubicin. A 2021 review by the phase 2 investigators reports that it was not superior. That trial did not require tumours to be tested for LHRH receptors, which the reviewers note when calling for better-designed studies.
Neutropenia and leucopenia were the main serious side effects in phase 2. Zoptarelin doxorubicin was never approved, and later registered trials in breast and urothelial cancer were terminated early.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Published Research
Studies of zoptarelin doxorubicin, from their PubMed abstracts.
Phase 2 in endometrial cancer
In 43 eligible women with LHRH receptor-positive advanced or recurrent endometrial cancer, 2 (5%) had complete and 8 (18%) partial remissions, 44% stable disease; median time to progression 7 months and overall survival 15 months; grade 3-4 neutropenia 12%, leucopenia 9%.
Phase 2 in platinum-resistant ovarian cancer
Of 42 women given 267 mg/m2 every 3 weeks, 6 (14.3%) had partial responses and 16 (38%) stable disease; median time to progression 12 weeks and overall survival 53 weeks; 93% of screened tumours expressed LHRH receptors.
Phase 2 in resistant prostate cancer
In 25 men with castration- and taxane-resistant prostate cancer given 210 mg/m2 every 3 weeks, 52% were progression-free at 12 weeks without limiting toxicity; median PFS 3.8 months and OS 6.0 months; pain improved in 59%.
First-in-human dose escalation
The first human study of AEZS-108, [D-Lys6]LHRH linked to doxorubicin, enrolled 17 women with metastatic or unresectable ovarian, endometrial or breast cancer to find the maximum tolerated dose and its pharmacokinetics.
Side Effects & Contraindications
Reported Side Effects
From the phase 2 trials above.
Contraindications & Cautions
There is no label; trials excluded these patients.
Legal Status
Zoptarelin doxorubicin was never approved.
Frequently Asked Questions
?What is zoptarelin doxorubicin?
An investigational conjugate of the hormone analogue [D-Lys6]LHRH and the chemotherapy drug doxorubicin, meant to deliver doxorubicin to cancers that carry LHRH receptors.
?Did it work?
It produced responses in phase 2 trials in endometrial, ovarian and prostate cancer, but in a 511-patient phase 3 trial in endometrial cancer it was not superior to doxorubicin alone.
?How is it related to leuprolide and other LHRH drugs?
Leuprolide, goserelin and triptorelin are LHRH analogues used to suppress sex hormones. Zoptarelin doxorubicin uses a similar analogue only as a homing signal to carry chemotherapy into receptor-positive cells.
References
- [other] PubChem CID 16134409, Zoptarelin doxorubicin: formula C91H117N19O26, molecular weight 1893.0. Read October 3, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/16134409
- [fda] FDA. Drugs@FDA (openFDA): no application on record for zoptarelin doxorubicin. Read October 3, 2026.
- [registry] ClinicalTrials.gov API v2, read October 3, 2026: NCT01767155 (phase 3 second-line endometrial cancer, 511, completed), NCT00569257 (phase 2, 85, completed), NCT01240629 (phase 1/2 prostate, 43, completed), NCT01698281 (phase 2 triple-negative breast, 7, terminated), NCT01234519 (phase 1/2 urothelial, 12, terminated).
- [clinical-trial] Emons G, et al. "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)." Int J Gynecol Cancer, 2014;24(2):260-5. PMID: 24418927.
- [clinical-trial] Emons G, et al. "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;133(3):427-32. PMID: 24713545.
- [clinical-trial] Yu SS, et al. "A Phase II Trial of AEZS-108 in Castration- and Taxane-Resistant Prostate Cancer." Clin Genitourin Cancer, 2017;15(6):742-749. PMID: 28668277.
- [pubmed] Emons G, et al. "Dose escalation and pharmacokinetic study of AEZS-108 (AN-152), an LHRH agonist linked to doxorubicin, in women with LHRH receptor-positive tumors." Gynecol Oncol, 2010;119(3):457-61. PMID: 20828803.
- [pubmed] Emons G, et al. "The Role of Gonadotropin-Releasing Hormone (GnRH) in Endometrial Cancer." Cells, 2021;10(2). PMID: 33535622.
Sources & Citations
Studies were read from their PubMed records and trial registrations from ClinicalTrials.gov, October 3, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.