TY - JOUR
T1 - Maximum androgen blockade in advanced prostate cancer
T2 - An overview of the randomised trials
AU - Dalesio, O.
AU - Van Tinteren, H.
AU - Clarke, M.
AU - Peto, R.
AU - Schroder, F. H.
N1 - Funding Information:
The chief acknowledgment is to the thousands of men who entered these studies, and to those who conducted trials and shared their data. The continuing collaboration is funded by support from the Netherlands Cancer Institute (NKI) to the NKI Biometrics Department, from the Imperial Cancer Research Fund and the UK Medical Research Council to the Clinical Trial Service Unit and Epidemiological Studies Unit, and from the Biomed II program of the European Union (grant PL-950113).
PY - 2000/4/29
Y1 - 2000/4/29
N2 - 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 nilutamide, 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%.
AB - 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 nilutamide, 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%.
UR - http://www.scopus.com/inward/record.url?scp=0034728828&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(00)02163-2
DO - 10.1016/S0140-6736(00)02163-2
M3 - Article
C2 - 10801170
AN - SCOPUS:0034728828
SN - 0140-6736
VL - 355
SP - 1491
EP - 1498
JO - Lancet
JF - Lancet
IS - 9214
ER -