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Genitourinary Cancer Case Study Single Case of a Complete Response in a Metastatic Urothelial Carcinoma Patient Treated with Zoptarelin Doxorubicin Gustavo Fernandez-Castro, 1 Andrew V Schally, 6 Tulay Koru-Sengul, 3 Merce Jorda, 4 Jaime R Merchan, 2 Aurea M Flores, 5 Maria Restrepo 1 and Norman L Block 4,6 1. Assistant Professor of Medicine, Department of Medicine; 2. Associate Professor of Medicine, Department of Medicine; 3. Assistant Professor, Department of Epidemiology and Public Health; 4. Professor, Department of Pathology, Sylvester Comprehensive Cancer Center of University of Miami Miller School of Medicine, Miami, Florida, US; 5. PhD, ClinRes Experts, Miami, Florida, US; 6. Professor, Veterans Affairs Medical Center, Miami, Florida, US Abstract Background: Zoptarelin doxorubicin (AEZS-108, AN-152) is an luteinising hormone-releasing hormone (LHRH)-cytotoxic hybrid drug consisting of an agonist coupled to the cytotoxic radical, doxorubicin. Methods: This is a single case report of a 66-year-old male who was diagnosed in May 2009 with metastatic urothelial carcinoma (UC) of the prostatic urethra. He presented with pelvic and retroperitoneal lymph nodes (LNs). Initially he was treated with cisplatin and gemzar, followed by radical cystoprostatectomy in October 2009. He relapsed in December 2009 and he received two more lines of chemotherapy with no response. The patient entered a phase I clinical trial with zoptarelin doxorubicin, in 2011. He received zoptarelin doxorubicin every 3 weeks for nine cycles from May to October 2011. Results: After two cycles of the investigational drug, all pain and palpable lymph neck nodes disappeared. A computed tomography (CT) scan 20 months post-treatment showed a complete response. Thirty months after treatment started, the patient is symptom free with no evidence of disease. Conclusions: This is the first case of a patient with LHRH-receptor (LHRH-R) positive UC treated with zoptarelin doxorubicin that has been reported. Considering the generally poor outcome of progressive UC and the short survival of these patients, the effect of this drug in this patient has been remarkable. Keywords Urothelial carcinoma, relapse, targeted, LHRH, AEZS-108, zoptarelin doxorubicin Disclosures: Andrew V Schally is listed as co-inventor on the Tulane University patents on AN-152 (AEZS-108). Gustavo Fernandez-Castro, Tulay Koru-Sengul, Merce Jorda, Jaime R Merchan, Aurea M Flores and Maria Restrepo have no conflicts of interest to declare. Norman L Block has stock ownership at Aeterna Zentaris. No funding was received in the publication of this article. Compliance with Ethics Guidelines: All procedures were followed in accordance with the responsible committee on human experimentation and with the Helsinki Declaration of 1975 and subsequent revisions. Informed consent was received from the patient involved in this case study. Received: 26 August 2014 Accepted: 5 December 2014 Citation: European Oncology & Haematology, 2014;10(2):82–5 Correspondence: Gustavo Fernandez-Castro, Division of Hematology/Oncology, Department of Medicine, University of Miami Miller School of Medicine, 1475 NW 12th Avenue, Miami, Florida, 33136 US. E: [email protected] It was estimated that more than 429,000 new cases of urothelial cancer (UC) were diagnosed worldwide in 2012. 1 There are limited treatments for locally advanced, unresectable, metastatic, platinum refractory UC. 2 As a single agent, doxorubicin has a response rate of 17 % in patients with previously treated and untreated advanced bladder cancer. Complete responses (CRs) are uncommon and the median duration of response was only 3 to 4 months. 3–6 Luteinising hormone-releasing hormone receptors (LHRH-Rs) are found on human cells of urothelial origin. Their high expression on the neoplastic cells and minimal expression in non-neoplastic cells, makes the LHRH-R an attractive therapeutic target. 7,8 Zoptarelin doxorubicin is an LHRH-cytotoxic hybrid drug, in which an LHRH agonist is coupled to the cytotoxic radical, doxorubicin. The binding permits zoptarelin doxorubicin to accumulate on the surface of cells expressing LHRH-R allowing the uptake of the doxorubicin, thereby exploiting these receptors to gain access to the targeted tumour cells. 82 Once internalised, the cytotoxic properties of doxorubicin provoke the anti-tumour response. 9,10 Phase I and II studies of zoptarelin doxorubicin have been reported in females with LHRH-R-positive endometrial and ovarian cancer and have demonstrated that this drug has activity and can be safely given with few side effects. 11,12 The first phase I study with zoptarelin doxorubicin included 17 women with epithelial cancers of ovary, endometrium or breast, and which were unresectable or metastatic. Each patient received intravenous doses of 10, 20, 40 or 80 mg/m 2 of zoptarelin doxorubicin, six received 160 mg/m 2 and seven 267 mg/m 2 at 3  week intervals. The half-life of Zoptarelin doxorubicin was estimated to be about 2 hours. Dose-limiting leukopenia and neutropenia were observed only at the highest dose. A total of six patients, three in each of the high-dose groups (three at 160  mg/m 2 ; three at 267  mg/m 2 ), showed responses to zoptarelin doxorubicin. The 267  mg/m 2 dose at intervals of 3 weeks was then selected as the starting dose for phase II studies. 11 The first phase II trial included 42 patients with taxane-resistant and © Touc h ME d ic al ME d ia 2014