Commentary on maximal androgen blockade in prostate cancer: A theory to put into practice?
Commentary on maximal androgen blockade in prostate cancer: A theory to put into practice?
复制标题
前列腺癌最大雄激素阻断的评论：付诸实践的理论？
DOI：
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发表时间：
1995
期刊：
影响因子：
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通讯作者：
L. Denis
中科院分区：
文献类型：
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作者：
L. Denis
患前列腺癌风险的人口在增加，公众对这种疾病的认识也在增加。自1945年首次提出最大雄激素阻断治疗（MAB）作为一种治疗非治愈性前列腺癌的有效方法以来，一直存在未解决的争议。我们如何解释单克隆抗体的数据，以便给每个病人最好的治疗建议？综合来看，使用药物阉割（黄体生成素-释放激素[LHRH]类似物加抗雄激素）与单独使用LHRH类似物的MAB研究尚无定论，尽管最大的研究显示MAB的客观益处。其余的研究没有足够的力量来显示预期的效应大小。手术阉割联合抗雄激素与单独手术阉割的单克隆抗体研究也给出了不一致的结果，尽管一项荟萃分析在反应的客观标准上支持单克隆抗体。在使用LHRH类似物与单独手术阉割的单克隆抗体试验中，一项是阳性的，其余两项是中性的。没有研究表明单克隆抗体比单纯的药物或手术阉割更糟糕。整体荟萃分析显示单抗有获益的趋势，但没有统计学意义。现有数据有力地表明，对某些亚组患者（包括那些病情轻微的患者）可能有特别的益处，但研究的数量太少，无法得出有效的结论。正在进行的INT 0105试验可能会让我们对这个问题和其他问题得出更确切的结论。与此同时，目前单克隆抗体方案的一个缺点是用尼鲁胺和氟他胺的副作用换取适度的临床优势。鉴于这种疾病是不可治愈的，改善生活质量是治疗的主要目标，而良好的治疗耐受性是实现这一目标的基础。在一项比较试验中，就治疗失败的时间而言，比卡鲁胺（Casodex）比氟他胺（分别与LHRH类似物联合使用）更有效，并且产生的腹泻发生率显着降低。总之，证据支持早期使用适当的激素治疗，这应该意味着药物或手术阉割，最好辅以抗雄激素。抗雄激素的耐受性是改善MAB患者生活质量的关键因素。©1995 Wiley‐Liss, Inc。
The population at risk of prostate cancer is on the increase, and so is public awareness of this disease. There has been an unresolved controversy surrounding the benefits of maximal androgen blockade (MAB) as a valid approach to treatment of non‐curative prostate cancer since it was first proposed in 1945. How are we to interpret the data on MAB in order to give each patient the best advice on treatment? Studies of MAB using medical castration (luteinizing hormone‐releasing hormone [LHRH] analogue plus antiandrogen) vs. LHRH analogues alone are inconclusive when viewed collectively, although the largest showed objective benefits for MAB. The remaining studies have insufficient power to show the expected effect size. Studies of MAB using surgical castration plus antiandrogen vs. surgical castration alone also gave inconsistent results, although a meta‐analysis is in favor of MAB on objective criteria of response. Among trials of MAB using an LHRH analogue vs. surgical castration alone, one is positive and the remaining two are neutral for MAB. No study shows MAB to be worse than either medical or surgical castration alone. An overall meta‐analysis shows a trend for benefit with MAB but is not statistically significant. The existing data have strongly suggested that there may be a particular benefit for certain subgroups of patients (including those with minimal disease) but numbers studied have been too small to allow valid conclusions. The INT 0105 trial in progress may permit firmer conclusions to be drawn on this and other questions. In the meantime one of the drawbacks to current MAB regimens is the exchange of modest clinical advantages for the side effects of nilutamide and flutamide. Given that the disease is noncurative, improved quality of life is the main goal of therapy, and excellent tolerability of treatment is fundamental to this. In a comparative trial, bicalutamide (Casodex) was more effective than flutamide (each in combination with an LHRH analogue) in terms of time to treatment failure and produced a significantly lower incidence of diarrhoea. In conclusion, the evidence supports early use of adequate hormonal treatment, and this should mean either medical or surgical castration, ideally augmented by an antiandrogen. Tolerability of the antiandrogen is a key consideration in gaining an improvement in quality of life with MAB. © 1995 Wiley‐Liss, Inc.