title: Intermittent Versus Continuous Androgen Deprivation Therapy in Patients with Relapsing or Locally Advanced Prostate Cancer: A Phase 3b Randomised Study (ICELAND).
abstract: BACKGROUND
  Intermittent androgen deprivation (IAD) has received increasing attention; however, the current literature is still limited, especially in nonmetastatic prostate cancer (PCa), and the relative efficacy and safety benefits of IAD versus continuous androgen deprivation (CAD) remain unclear.
  
  
  OBJECTIVE
  To add to the knowledge base regarding efficacy and potential benefits, including reduced side effects and improved quality of life (QoL), of IAD versus CAD in patients with nonmetastatic relapsing or locally advanced PCa.
  
  
  METHODS
  A 42-mo phase 3b open-label randomised study in 933 patients from 20 European countries.
  
  
  METHODS
  Following a 6-mo induction with leuprorelin acetate (Eligard) 22.5mg 3-mo depot, patients were randomised to CAD or IAD with leuprorelin for 36 mo.
  
  
  METHODS
  The primary end point was time to prostate-specific antigen (PSA) progression while receiving luteinising hormone-releasing hormone agonist, defined as three consecutive increasing PSA values ≥ 4 ng/ml ≥ 2 wk apart. Secondary end points included PSA progression-free survival (PFS), overall survival (OS), testosterone levels, performance status, and QoL.
  
  
  CONCLUSIONS
  A total of 933 patients entered the induction phase; 701 were randomised. The median number of injections administered after randomisation was 12 (range: 1-12) for the CAD group and 3 (range: 1-10) for the IAD group. There were no statistically significant or clinically relevant differences between the groups for time to PSA progression, PSA PFS, OS, mean PSA levels over time, or QoL. A similar number of adverse events was observed in each group; the most common were hot flushes and hypertension. Study limitations include the open-label design and absence of formal testosterone recovery assessment.
  
  
  CONCLUSIONS
  IAD and CAD demonstrated similar efficacy, tolerability, and QoL in men with nonmetastatic PCa. The principal benefit of IAD compared with CAD is a potential cost reduction with comparable OS rates. There are no apparent QoL benefits.
  
  
  RESULTS
  This randomised trial showed that both intermittent and continuous hormone therapy had similar efficacy, tolerability, and quality-of-life profiles in patients with relapsing M0 or locally advanced prostate cancer. Intermittent therapy may be a valid option for selected patients.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT00378690.
authors.affiliation: Clinic E Cavell and University of Brussels, Brussels, Belgium. Electronic address: profschulman@gmail.com.
authors.forename: Claude
authors.initials: C
authors.lastname: Schulman
authors.affiliation: Department of Urology, Ziekenhuis Groep Twente, Hengelo, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Cornel
authors.affiliation: Department of Onco-Urology, Cancer Research Centre, Moscow, Russia.
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Matveev
authors.affiliation: Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland.
authors.forename: Teuvo L
authors.initials: TL
authors.lastname: Tammela
authors.affiliation: Clinic of Urology and Robotic Surgery, Masaryk's Hospital, Usti nad Labem, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Schraml
authors.affiliation: Department of Urology and Transplantation, Caen University Hospital, Caen, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Bensadoun
authors.affiliation: Warnack Private Practice, Hagenow, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Warnack
authors.affiliation: Department of Urology, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors.forename: Raj
authors.initials: R
authors.lastname: Persad
authors.affiliation: Second Urology Department, Medical University of Lodz, Lodz, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Salagierski
authors.affiliation: A Coruña University Hospital, Urology, A Coruña, Spain, and Urology Department and Kidney Transplant Unit, Salamanca University Hospital, Salamanca, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Gómez Veiga
authors.affiliation: Astellas Pharma Global Development, Leiden, The Netherlands.
authors.forename: Edwina
authors.initials: E
authors.lastname: Baskin-Bey
authors.affiliation: Astellas Pharma Global Development, Leiden, The Netherlands.
authors.forename: Beatriz
authors.initials: B
authors.lastname: López
authors.affiliation: Institut de Recherche Clinique, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tombal
mesh_terms: D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D003692:Delayed-Action Preparations; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005060:Europe; D006304:Health Status; D006801:Humans; D007610:Kallikreins / Q000097:blood; D053208:Kaplan-Meier Estimate; D016729:Leuprolide / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; C493311:luprolide acetate gel depot; D013739:Testosterone; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D016729:Leuprolide
keywords: Androgen deprivation; Continuous androgen deprivation; Intermittent androgen deprivation; Nonmetastatic; Prostate cancer; Prostate-specific antigen progression; Testosterone