Gynecological cancers, such as breast, ovarian, and endometrial carcinoma can be lethal. According to the Annals of Oncology (2004; 15:1149-50) each year approximately 38,000 women will be diagnosed with endometrium cancer, the most common gynaecologic malignancy accounting for 6% of all cancers in women. The same report estimates 9,000 deaths caused by the disease annually. The majority of the reported cases occur in postmenopausal women, with the largest number of women developing their cancers during their sixth decade.Another common gynaecologic malignancies and the fifth most frequent cause of cancer death in women is ovarian cancer. Most cases of ovarian cancer occure in women between 50 and 75 years of age and accounts for 4% of all cancer diagnoses in women and 5% of all cancer deaths. According to the Gynaecologic Oncology (2004; 92:819-26), approximately 26,000 new cases and 17,000 deaths from this disease are estimated in the European community every year.
New treatment option in clinical trialGynecological cancers such as breast, ovarian, and endometrial carcinoma express receptors for luteinizing hormone-releasing hormone (LHRH), bombesin/gastrin-releasing peptide (BN/GRP), and somatostatin (SST). These tumors are therefore suitable candidates for targeted therapy with cytotoxic hybrid molecules consisting of a cytotoxic radical and a peptide hormone analogue as a carrier. These compounds have been shown to be more active and less toxic in vivo than nontargeted chemotherapy in models of various human cancers which express the respective receptors.AEZS-108 (formerly AN-152), is a potential new drug for the treatment of endometrial cancer, offers great promise in a Phase II clinical trial in patients with advanced or recurrent disease.The new drug candidate offers a new targeting concept in oncology using a cytotoxic peptide conjugate, a hybrid molecule composed of a synthetic peptide carrier and a well-known cytotoxic agent, doxorubicin. The design of this product allows for the specific binding and selective uptake of the cytotoxic conjugate by LHRH-receptor positive tumors. The binding of AEZS-108 to cancerous cells that express these receptors, results in its accumulation and preferential uptake in the malignant tissueIn a personalized health care approach, the study included patients with tumors expressing luteinizing hormone-releasing hormone (LHRH) receptors, the key element in the targeting mechanism of AEZS-108. Under the coordination of Prof. Gunter Emons, MD, Chairman of the Department of Obstetrics & Gynecology at the University of Gottingen, Germany, this open-label, multi-center and multi-national Phase II study AGO-GYN 5, is being conducted by the German AGO Study Group (Arbeitsgemeinschaft Gynakologische Onkologie/Gynaecological Oncology Working Group.Preliminary ResultsThe preliminary evaluation of data shows that the study AGO-GYN 5 investigation AEZS-108, met its predefined primary efficacy endpoint of 5 or more responder patients with endometrial cancer. The study is currently ongoing, and responders, as well as patients with stable disease after completion of treatment with AEZS-108, will be followed to assess the duration of progression-free survival and, ultimately, overall survival. Detailed analyses of the study results will be presented at forthcoming scientific conferences.Juergen Engel, Ph.D., President and Chief Executive Officer at AEterna Zentaris stated, “We are pleased with the progress of this Phase 2 program. Along with the recently disclosed positive results for the ovarian cancer indication, the good news for the endometrial cancer indication provides us with an even stronger basis to take the next steps in the development of AEZS-108 in gynaecological cancers.”Phase II trialIn a Phase II study program entitled, “The antitumoral activity and safety of AEZS-108 (AN-152), a LHRH agonist linked doxorubicin in women with LHRH-receptor positive gynaecological tumors”, patients with tumors expressing LHRH receptors are administered an intravenous infusion of 267 mg/m2 of AEZS-108 over a period of 2 hours, every Day 1 of a 21-day (3-week) cycle. The proposed duration of the study treatment is 6, 3-week cycles.Study AGO-GYN 5 is performed with 14 centers of the German Gynaecological Oncology Working Group and 3 other trial centers in Europe.The program was planned to include up to 82 evaluable patients, up to 41 with a diagnosis of platinum-resistant and taxane-pretreated ovarian cancer, (for which positive results were disclosed on November 2, 2009) and up to 41 with advanced or recurrent endometrial cancer. For both indications, patient recruitment was planned in 2 stages, with 21 and 20 patients, respectively, and the primary efficacy endpoint at the end of stage 2 was defined as 5 or more patients with partial or complete tumor responses according to Response Evaluation Criteria in Solid Tumors (RECIST) and/or Gynaecologic Cancer Intergroup (GCIG) guidelines. Secondary endpoints include time to progression, survival, toxicity as well as adverse effects.AEZS-108 is under development by AEterna Zentaris Inc, a global biopharmaceutical company focusing on endocrine therapy and oncology.Picture Credit: Anatomy of the female reproductive system. The organs in the female reproductive system include the uterus, ovaries, fallopian tubes, cervix, and vagina. The uterus has a muscular outer layer called the myometrium and an inner lining called the endometrium. Illustration courtesy of the American Society of Clinical Oncology.
