Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: results from a randomised phase III study of the South European Uroncological group

Fernando E.C. Calais da Silva, Aldo V. Bono, Peter Whelan, Maurizio Brausi, Anton Marques Queimadelos, Jose A. Portillo Martin, Ziya Kirkali, Fernando M.V. Calais da Silva, Chris Robertson

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

Background: Few randomised studies have compared intermittent hormonal therapy with continuous therapy for the treatment of advanced prostate cancer Objective: To determine if intermittent therapy is associated with a shorter time to progression. Design Setting and participants: 766 patients with locally advanced or metastatic prostate cancer received a three month induction treatment. 626 patients whose PSA decreased below 4 ng/ml or to 80% below the initial value, were randomised. Intervention: Patients received cyproterone acetate (CPA) 200 mg for two weeks and then monthly depot injections of a 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 a LHRH analogue. Measurements. Primary outcome was time to subjective or objective progression. Secondary outcomes were survival and quality of life. Time off therapy in the intermittent arm was also recorded. Results and Limitations: 127 intermittent and 107 continuous patients progressed with hazard ratio 0.81 (95% CI 0.63 to 1.05), p=0.11. There was no difference in survival, with hazard ratio 0.99 (95% CI 0.80 to 1.23) and 170 deaths on the intermittent and 169 on the continuous arm. A slight excess of cancer deaths in the intermittent treatment arm (106 versus 84) is balanced by a slight excess of cardiovascular deaths in the continuous arm (52 versus 41). Side effects are more pronounced on the continuous arm. Men treated with intermittent therapy reported better sexual function. Median time off therapy for the intermittent patients was 52 weeks (95% CI 39.4, 65.7). Conclusion: Intermittent therapy should be considered for use in routine practice since it is associated with no reduction in survival, no clinically meaningful impairment in quality of life, better sexual activity, and considerable economic benefit to individual and community.
LanguageEnglish
Pages1269-1277
Number of pages8
JournalEuropean Urology
Volume55
Issue number6
DOIs
Publication statusPublished - Jun 2009

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Androgens
Prostatic Neoplasms
Cyproterone Acetate
Therapeutics
Gonadotropin-Releasing Hormone
Quality of Life
Survival
Sexual Behavior
Economics
Injections

Keywords

  • prostate cancer
  • hormonal therapy
  • intermittent therapy
  • quality of life

Cite this

Calais da Silva, Fernando E.C. ; Bono, Aldo V. ; Whelan, Peter ; Brausi, Maurizio ; Queimadelos, Anton Marques ; Martin, Jose A. Portillo ; Kirkali, Ziya ; Calais da Silva, Fernando M.V. ; Robertson, Chris. / Intermittent androgen deprivation for locally advanced and metastatic prostate cancer : results from a randomised phase III study of the South European Uroncological group. In: European Urology. 2009 ; Vol. 55, No. 6. pp. 1269-1277.
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abstract = "Background: Few randomised studies have compared intermittent hormonal therapy with continuous therapy for the treatment of advanced prostate cancer Objective: To determine if intermittent therapy is associated with a shorter time to progression. Design Setting and participants: 766 patients with locally advanced or metastatic prostate cancer received a three month induction treatment. 626 patients whose PSA decreased below 4 ng/ml or to 80{\%} below the initial value, were randomised. Intervention: Patients received cyproterone acetate (CPA) 200 mg for two weeks and then monthly depot injections of a 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 a LHRH analogue. Measurements. Primary outcome was time to subjective or objective progression. Secondary outcomes were survival and quality of life. Time off therapy in the intermittent arm was also recorded. Results and Limitations: 127 intermittent and 107 continuous patients progressed with hazard ratio 0.81 (95{\%} CI 0.63 to 1.05), p=0.11. There was no difference in survival, with hazard ratio 0.99 (95{\%} CI 0.80 to 1.23) and 170 deaths on the intermittent and 169 on the continuous arm. A slight excess of cancer deaths in the intermittent treatment arm (106 versus 84) is balanced by a slight excess of cardiovascular deaths in the continuous arm (52 versus 41). Side effects are more pronounced on the continuous arm. Men treated with intermittent therapy reported better sexual function. Median time off therapy for the intermittent patients was 52 weeks (95{\%} CI 39.4, 65.7). Conclusion: Intermittent therapy should be considered for use in routine practice since it is associated with no reduction in survival, no clinically meaningful impairment in quality of life, better sexual activity, and considerable economic benefit to individual and community.",
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Intermittent androgen deprivation for locally advanced and metastatic prostate cancer : results from a randomised phase III study of the South European Uroncological group. / Calais da Silva, Fernando E.C.; Bono, Aldo V.; Whelan, Peter; Brausi, Maurizio; Queimadelos, Anton Marques; Martin, Jose A. Portillo; Kirkali, Ziya; Calais da Silva, Fernando M.V.; Robertson, Chris.

In: European Urology, Vol. 55, No. 6, 06.2009, p. 1269-1277.

Research output: Contribution to journalArticle

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T1 - Intermittent androgen deprivation for locally advanced and metastatic prostate cancer

T2 - European Urology

AU - Calais da Silva, Fernando E.C.

AU - Bono, Aldo V.

AU - Whelan, Peter

AU - Brausi, Maurizio

AU - Queimadelos, Anton Marques

AU - Martin, Jose A. Portillo

AU - Kirkali, Ziya

AU - Calais da Silva, Fernando M.V.

AU - Robertson, Chris

PY - 2009/6

Y1 - 2009/6

N2 - Background: Few randomised studies have compared intermittent hormonal therapy with continuous therapy for the treatment of advanced prostate cancer Objective: To determine if intermittent therapy is associated with a shorter time to progression. Design Setting and participants: 766 patients with locally advanced or metastatic prostate cancer received a three month induction treatment. 626 patients whose PSA decreased below 4 ng/ml or to 80% below the initial value, were randomised. Intervention: Patients received cyproterone acetate (CPA) 200 mg for two weeks and then monthly depot injections of a 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 a LHRH analogue. Measurements. Primary outcome was time to subjective or objective progression. Secondary outcomes were survival and quality of life. Time off therapy in the intermittent arm was also recorded. Results and Limitations: 127 intermittent and 107 continuous patients progressed with hazard ratio 0.81 (95% CI 0.63 to 1.05), p=0.11. There was no difference in survival, with hazard ratio 0.99 (95% CI 0.80 to 1.23) and 170 deaths on the intermittent and 169 on the continuous arm. A slight excess of cancer deaths in the intermittent treatment arm (106 versus 84) is balanced by a slight excess of cardiovascular deaths in the continuous arm (52 versus 41). Side effects are more pronounced on the continuous arm. Men treated with intermittent therapy reported better sexual function. Median time off therapy for the intermittent patients was 52 weeks (95% CI 39.4, 65.7). Conclusion: Intermittent therapy should be considered for use in routine practice since it is associated with no reduction in survival, no clinically meaningful impairment in quality of life, better sexual activity, and considerable economic benefit to individual and community.

AB - Background: Few randomised studies have compared intermittent hormonal therapy with continuous therapy for the treatment of advanced prostate cancer Objective: To determine if intermittent therapy is associated with a shorter time to progression. Design Setting and participants: 766 patients with locally advanced or metastatic prostate cancer received a three month induction treatment. 626 patients whose PSA decreased below 4 ng/ml or to 80% below the initial value, were randomised. Intervention: Patients received cyproterone acetate (CPA) 200 mg for two weeks and then monthly depot injections of a 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 a LHRH analogue. Measurements. Primary outcome was time to subjective or objective progression. Secondary outcomes were survival and quality of life. Time off therapy in the intermittent arm was also recorded. Results and Limitations: 127 intermittent and 107 continuous patients progressed with hazard ratio 0.81 (95% CI 0.63 to 1.05), p=0.11. There was no difference in survival, with hazard ratio 0.99 (95% CI 0.80 to 1.23) and 170 deaths on the intermittent and 169 on the continuous arm. A slight excess of cancer deaths in the intermittent treatment arm (106 versus 84) is balanced by a slight excess of cardiovascular deaths in the continuous arm (52 versus 41). Side effects are more pronounced on the continuous arm. Men treated with intermittent therapy reported better sexual function. Median time off therapy for the intermittent patients was 52 weeks (95% CI 39.4, 65.7). Conclusion: Intermittent therapy should be considered for use in routine practice since it is associated with no reduction in survival, no clinically meaningful impairment in quality of life, better sexual activity, and considerable economic benefit to individual and community.

KW - prostate cancer

KW - hormonal therapy

KW - intermittent therapy

KW - quality of life

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