Intermittent Androgen Deprivation for Locally Advanced and Metastatic Prostate Cancer: Results from a Randomised Phase 3 Study of the South European Uroncological Group

• Published in: European urology Vol. 55; no. 6; pp. 1269 - 1277
• Main Authors: Calais da Silva, Fernando E.C, Bono, Aldo V, Whelan, Peter, Brausi, Maurizio, Marques Queimadelos, Anton, Martin, Jose A. Portillo, Kirkali, Ziya, Calais da Silva, Fernando M.V, Robertson, Chris
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.06.2009; Elsevier
• Subjects: Aged; Androgen Antagonists - administration & dosage; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Confidence Intervals; Cyproterone Acetate - administration & dosage; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Europe; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - therapeutic use; Gynecology. Andrology. Obstetrics; Hormonal therapy; Humans; Intermittent therapy; Male; Male genital diseases; Maximum Tolerated Dose; Medical sciences; Middle Aged; Neoplasm Invasiveness - pathology; Neoplasm Metastasis - drug therapy; Neoplasm Recurrence, Local - mortality; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Nephrology. Urinary tract diseases; Prognosis; Prostate cancer; Prostate-Specific Antigen - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Quality of Life; Risk Assessment; Survival Analysis; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urology; Europe; Prostate cancer; Intermittent therapy; Hormonal therapy; Quality of life; Phase III trial; Nephrology; Urinary system disease; Androgen deprivation therapy; Prostate disease; Hormone therapy; South; Malignant tumor; Metastasis; Urology; Randomization; Intermittent; Androgen deprivation; Advanced stage; Metastatic; Locally advanced stage; Male genital diseases; Cancer
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2009.02.016

Abstract Background Few randomised studies have compared intermittent hormonal therapy (IHT) with continuous therapy for the treatment of advanced prostate cancer (PCa). Objective To determine whether intermittent therapy is associated with a shorter time to progression. Design, setting, and participants 766 patients with locally advanced or metastatic PCa received a 3-mo induction treatment. The 626 patients whose prostate-specific antigen (PSA) level decreased to <4 ng/ml or to 80% below the initial value were randomised. Intervention Patients received cyproterone acetate (CPA) 200 mg for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH) analogue plus 200 mg of CPA daily during induction. Patients randomised to the intermittent arm ceased treatment, while those randomised to the continuous arm received 200 mg of CPA daily plus an LHRH analogue. Measurements Primary outcome measurement was time to subjective or objective progression. Secondary outcomes were survival and quality of life (QoL). Time off therapy in the intermittent arm was also recorded. Results and limitations 127 patients from the intermittent arm and 107 patients from the continuous arm progressed, with a hazard ratio (HR) of 0.81 (95% confidence interval [CI]: 0.63–1.05, p = 0.11). There was no difference in survival, with an HR of 0.99 (95% CI: 0.80–1.23) and 170 deaths in the intermittent arm and 169 deaths in the continuous arm. The greater number of cancer deaths in the intermittent treatment arm (106 vs 84) was balanced by a greater number of cardiovascular deaths in the continuous arm (52 vs 41). Side-effects were more pronounced in the continuous arm. Men treated with intermittent therapy reported better sexual function. Median time off therapy for the intermittent patients was 52 wk (95% CI: 39.4–65.7). Conclusions IHT should be considered for use in routine practice because it is associated with no reduction in survival, no clinically meaningful impairment in QoL, better sexual activity, and considerable economic benefit to the individual and the community.