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Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials

Lookup NU author(s): Christopher Hill


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Background In advanced prostate cancer, androgen suppression (AS) by surgery or drugs controls testicular hormone secretion, and the further addition of an antiandrogen such as nitutamide, flutamide, or cyproterone acetate is referred to as maximum androgen blockade (MAB), The aim of this overview was to compare the effects on the duration of survival of MAB and of AS alone. Methods The collaborative meta-analysis of 27 randomised trials involved central reanalysis of the data on each of 8275 men (98% of those ever randomised in trials of MAB vs AS) with metastatic (88%) or locally advanced (12%) prostate cancer. Half were over 70 years of age, and follow-up was typically for about 5 years. Findings 5932 (72%) men have died; of the deaths for which causes were provided, about 80% were attributed to prostate cancer. 5-year survival was 25.4% with MAB versus 23.6% with AS alone, a non-significant gain of 1.8% (SE 1.3; logrank 2p=0.11). There was no significant heterogeneity in the treatment effect (MAB vs AS) with respect to age or disease stage. The results for cyproterone acetate, which accounted for only a fifth of the evidence, appeared slightly unfavourable to MAB (5-year survival 15.4% MAB vs 18.1% AS alone; difference -2.8% [SE 2.4]; logrank 2p=0.04 adverse), whereas those for nilutamide and flutamide appeared slightly favourable (5-year survival 27.6% MAB vs 24.7% AS alone; difference 2.9% [SE 1.3]; logrank 2p=0.005). Non-prostate-cancer deaths (although not clearly significantly affected by treatment) accounted for some of the apparently adverse effects of cyproterone acetate. Interpretation In advanced prostate cancer, addition of an antiandrogen to AS improved the 5-year survival by about 2% or 3% (depending on whether the analysis includes or excludes the cyproterone acetate trials), but the range of uncertainty as to the true size of this benefit runs from about 0% to about 5%.

Publication metadata

Author(s): Dalesio O, van Tinteren H, Clarke M, Peto R, Schroder FH, Dechering I, Evans V, Godwin J, Blumenstein BA, Crawford ED, Denis L, Hall R, Hill C, Iversen P, Shipley WU, Soloway M, Sylvester R, Prostate Canc Trialists Collaborat

Publication type: Article

Publication status: Published

Journal: Lancet

Year: 2000

Volume: 355

Issue: 9214

Pages: 1491-1498

ISSN (print): 0140-6736

ISSN (electronic): 1474-547X

Publisher: The Lancet Publishing Group


DOI: 10.1016/S0140-6736(00)02163-2


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