title: Degarelix for the treatment of advanced prostate cancer compared with GnRh-Agonists: a systematic review and meta-analysis.
abstract: BACKGROUND
  Hormone therapy is currently the mainstay in the management of locally advanced and metastatic prostate cancer. We performed a systematic review to compare safety, efficacy and effectiveness of degarelix, a new gonadotropin-releasing hormone (GnRH) antagonist (blocker), versus gonadotropin-releasing hormone (GnRH) agonists.
  
  
  METHODS
  MEDLINE, Web of Science and the Cochrane library were searched to identify all of the published Randomized Controlled Trials (RCTs) that used degarelix versus gonadotropin-releasing hormone agonists with or without anti-androgen therapy for the treatment of prostate cancer. We performed meta-analysis of extracted data on safety and efficacy of the target medication.
  
  
  RESULTS
  Six studies were included. They involved a total of 2296 patients which were used in the meta-analysis. Follow-up times after treatment were between 12 weeks and 12 months. Three of six RCTs compared degarelix with goserelin and the others compared it with leuprolide. Meta-analysis on safety outcomes revealed that the only statistically significant difference between the degarelix treated group and GnRH agonists treated group was complication in the injection site which was higher in degarelix-treated group (OR= 46.34, 95% CI: 15.79 to 136, p<0.001). Although general mortality rate was lower in degarelix-treated group (OR= 2.06, 95% CI: 1.08 to 3.93, p=0.03); mortality due to the drug side effects was not different. Meta-analysis of efficacy data also showed that International Prostate Symptom Score (IPSS) reduction at week 12, (MD=-1.85, 95% CI: -2.97 to - 0.72, p=0.001) and Testosterone reduction between day 1-28, (OR=11.58, 95% CI: 5.77 to 23.22, p<0.001) was statistically higher in degarelix-treated group. Testosterone reduction after day 28 and prostate volume reduction did not have significant difference.
  
  
  CONCLUSIONS
  Our meta-analysis indicates that, compared with GnRH agonists, degarelix has significantly more effects on lower urinary tract symptoms and also Prostate Specific Antigen (PSA) and testosterone reduction in the first month of the treatment. Except minor complications in the injection site like pain, erythema and swelling, there is no increase in major side effects and mortality due to degarelix. This is while the effect on testosterone and PSA after the first month of treatment is not statistically different between the two groups.
authors.affiliation: Associate Professor, Food and Drug Research Center, Clinical Trials Group, Iran Food and Drug Administration, Tehran, Iran. a.hosseini@fda.gov.ir .
authors.forename: Seyed Alireza
authors.initials: SA
authors.lastname: Hosseini
authors.affiliation: Assistant Professor in Community Medicine, Community Based Participatory Research Center, Iranian Institute for Reduction of High-Risk Behaviors, & Center for Academic and Health Policy, Tehran University of Medical Sciences, Tehran, Iran. frajabi@tums.ac.ir.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Rajabi
authors.affiliation: Associate Professor, Department of Health Management and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. akbarisari@tums.ac.ir .
authors.forename: Ali
authors.initials: A
authors.lastname: Akbari Sari
authors.affiliation: Associate Professor of Urology, Department of Urology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran. drayati_mohsen@yahoo.com .
authors.forename: Mohsen
authors.initials: M
authors.lastname: Ayati
authors.affiliation: MSc, Health Technology Assessment, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. saeedheidari.hta@gmail.com.
authors.forename: Saeed
authors.initials: S
authors.lastname: Heidari
authors.affiliation: MSc, Health Technology Assessment, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. fgh12@ymail.com .
authors.forename: Fawzieh
authors.initials: F
authors.lastname: Ghamary
keywords: Degarelix; Efficacy; GnRH Agonists; Goserelin; Leuprolide; Meta-analysis; Prostate cancer; Safety