title: Risks of Serious Toxicities from Intermittent versus Continuous Androgen Deprivation Therapy for Advanced Prostate Cancer: A Population Based Study.
abstract: Randomized trials have shown that intermittent androgen deprivation therapy for patients with advanced prostate cancer may improve sexual and physical functioning compared to continuous androgen deprivation therapy without compromising survival. To our knowledge it is unknown whether intermittent androgen deprivation therapy alters the risk of serious toxicities associated with continuous androgen deprivation therapy.
  
  
  
  We performed a population based cohort study of 9,772 men 66 years old or older who were diagnosed with advanced prostate cancer from 2002 to 2011 and treated with androgen deprivation therapy. Intermittent androgen deprivation therapy was defined as a single 90-day interval between 2 androgen deprivation therapy sessions during which patients visited their physicians or underwent prostate specific antigen testing. Outcomes included acute myocardial infarction, stroke, heart failure, type 2 diabetes and fracture. We used Cox proportional hazard models to estimate the HRs of the comparative risk of serious toxicities between intermittent and continuous androgen deprivation therapy.
  
  
  
  A total of 2,113 (22%), 769 (9%) and 899 men (9%) had a new cardiovascular event, diabetes or fracture, respectively, within 5 years of starting androgen deprivation therapy. Compared to the continuous androgen deprivation therapy group, the intermittent therapy group was at lower risk for serious cardiovascular events (HR 0.64, 95% CI 0.53-0.77), particularly in reducing the risk of heart failure (HR 0.62, 95% CI 0.49-0.78) and fracture (HR 0.52, 95% CI 0.38-0.70, each p <0.0001).
  
  
  
  Intermittent androgen deprivation therapy was associated with a lower risk of heart failure and fracture compared to continuous androgen deprivation therapy. This raises toxicity concerns for continuous relative to intermittent therapy and suggests that intermittent androgen deprivation therapy may represent a safer therapeutic choice in elderly men with advanced prostate cancer.
authors.affiliation: Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, D.C.. Electronic address: hueiting.tsai@georgetown.edu.
authors.forename: Huei-Ting
authors.initials: HT
authors.lastname: Tsai
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Department of Medicine, Georgetown University Medical Center, Georgetown University, Washington, D.C.
authors.forename: George K
authors.initials: GK
authors.lastname: Philips
authors.affiliation: Division of Cardiology, MedStar Washington Hospital Center, Washington, D.C.
authors.forename: Ana
authors.initials: A
authors.lastname: Barac
authors.affiliation: Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, D.C.
authors.forename: Alex Z
authors.initials: AZ
authors.lastname: Fu
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: David F
authors.initials: DF
authors.lastname: Penson
authors.affiliation: Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, D.C.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, D.C.
authors.forename: Arnold L
authors.initials: AL
authors.lastname: Potosky
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012042:Registries; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal
keywords: androgen antagonists; antineoplastic agents; drug related side effects and adverse reactions; hormonal; prostatic neoplasms; risk