title: Intermittent LHRH therapy in the management of castrate-resistant prostate cancer (CRPCa): results of a multi-institutional randomized prospective clinical trial.
abstract: BACKGROUND
  Patients who develop castration-resistant prostate cancer (CRPCa) typically continue on androgen deprivation therapy (ADT). Whether these patients need to remain on ADT has not been well studied. We conducted a multicenter randomized trial to compare an intermittent versus continuous approach to ADT in CRPCa patients. Overall survival, health-related quality of life (QOL), and cost were the main endpoints.
  
  
  METHODS
  CRPCa patients were randomized 2:1 to intermittent or continuous luteinizing hormone-releasing hormone agonists (LHRHa). Patients were followed with clinical assessments, laboratory investigations, and QOL questionnaires (EORTC QLQ-C30 or PROSQOLI) every 2 months. If the serum testosterone rose above castrate levels (1.75 nmol/L), LHRHa were reinitiated. The study was designed to close if >50% of patients needed to restart ADT in the intermittent arm.
  
  
  RESULTS
  Thirty-one patients were followed with a median follow-up of 26.8 months-18 in the intermittent arm and 13 in the continuous. Twelve of 18 patients on the intermittent arm were reinitiated on LHRHa at a median time of 17.9 months. There was no difference in overall or cancer-specific survival between the 2 arms. There was no statistically significant difference in QOL between the 2 arms at 0 and 12 months. The total mean costs at 24 months were significantly lower in the intermittent arm ($3135 vs. $8253 Canadian dollars, P=0.0167) compared with the continuous. The main limitation of this study is the small sample size.
  
  
  CONCLUSIONS
  We have observed that intermittent ADT in patients with CRPCa, using a testosterone of >1.75 ngmol/L as a trigger to reinitiate LHRHa, results in a substantial cost savings with no negative impact on oncologic and QOL outcomes.
authors.affiliation: Departments of *Urology †Medicine and Urology ‡Radiation Oncology §Atlantic Clinical Cancer Research Unit (ACCRU), Capital Health #Medicine **Urology, Centre for Clinical Research, Dalhousie University, Halifax, NS ∥Department of Medical Oncology, University of Calgary, Tom Baker Cancer Center, Calgary ¶Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Organ
authors.forename: Lori
authors.initials: L
authors.lastname: Wood
authors.forename: Derek
authors.initials: D
authors.lastname: Wilke
authors.forename: Chris
authors.initials: C
authors.lastname: Skedgel
authors.forename: Tina
authors.initials: T
authors.lastname: Cheng
authors.forename: Scott
authors.initials: S
authors.lastname: North
authors.forename: Kara
authors.initials: K
authors.lastname: Thompson
authors.forename: Susan
authors.initials: S
authors.lastname: Winch
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rendon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003365:Costs and Cost Analysis; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000191:economics / Q000401:mortality; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome
chemical_list: D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D017430:Prostate-Specific Antigen