晚期前列腺癌的最大雄激素阻断：随机试验综述。前列腺癌试验协作组

Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Prostate Cancer Trialists' Collaborative Group.

出版信息

Lancet. 2000 Apr 29;355(9214):1491-8.

Abstract

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%.

摘要

背景

在晚期前列腺癌中，通过手术或药物进行雄激素抑制（AS）可控制睾丸激素分泌，进一步添加诸如尼鲁米特、氟他胺或醋酸环丙孕酮等抗雄激素药物被称为最大雄激素阻断（MAB）。本综述的目的是比较MAB与单纯AS对生存时间的影响。

方法

对27项随机试验进行协作荟萃分析，对8275名男性（占MAB与AS试验中所有随机分组者的98%）的数据进行集中重新分析，这些男性患有转移性（88%）或局部晚期（12%）前列腺癌。一半患者年龄超过70岁，随访时间通常约为5年。

结果

5932名（72%）男性死亡；在提供死因的死亡病例中，约80%归因于前列腺癌。MAB组的5年生存率为25.4%，单纯AS组为23.6%，非显著提高了1.8%（标准误1.3；对数秩检验2p = 0.11）。在年龄或疾病分期方面，治疗效果（MAB与AS）无显著异质性。仅占证据五分之一的醋酸环丙孕酮的结果似乎对MAB略有不利（MAB组5年生存率15.4%，单纯AS组18.1%；差异-2.8%[标准误2.4]；对数秩检验2p = 0.04不利），而尼鲁米特和氟他胺的结果似乎略有有利（MAB组5年生存率27.6%，单纯AS组24.7%；差异2.9%[标准误1.3]；对数秩检验2p = 0.005）。非前列腺癌死亡（尽管未明显受治疗显著影响）是醋酸环丙孕酮一些明显不利影响的部分原因。