Department of Urology, Lund University, Malmö University Hospital, S-224 01, Malmö, Sweden.
Eur Urol. 2010 Jan;57(1):49-59. doi: 10.1016/j.eururo.2009.07.049. Epub 2009 Aug 7.
The well-known side-effect profile of androgen-deprivation therapy (ADT) has significant quality-of-life (QoL) implications. Intermittent androgen deprivation (IAD) alternates androgen blockade with treatment cessation to allow hormonal recovery between treatment cycles, thus potentially improving tolerability and QoL.
To evaluate available evidence regarding the efficacy and tolerability of IAD and assess its value in the treatment of prostate cancer (PCa).
Key phase 2/3 clinical trials of IAD in PCa published within the last 10 yr were identified on Medline using the terms prostatic neoplasms [MeSH], intermittent androgen suppression, intermittent hormonal deprivation, intermittent androgen deprivation, and intermittent hormonal therapy. Abstracts from trials reported at 2008-2009 conferences were also included.
Data from 19 phase 2 studies are discussed with respect to prostate-specific antigen values for treatment suspension/reinitiation, treatment regimens, cycle lengths, testosterone normalisation, and tolerability. Outcome data were promising: Most trials reported an improvement in QoL during the off-therapy periods. Interim data from eight phase 3 trials comparing IAD and continuous androgen deprivation (CAD) support the phase 2 results. IAD generally showed comparable efficacy to CAD with respect to various outcomes, including biochemical progression, progression-free survival, and overall survival. However, IAD was significantly better than CAD with respect to 3-yr risk of progression in one study, and it demonstrated tolerability benefits, particularly with respect to sexual function. Patients most likely to benefit from IAD and factors predictive of poor response are also discussed.
IAD seems to be as effective as CAD while showing tolerability and QoL advantages, especially recovery of sexual potency; however, there are as yet insufficient data to determine whether IAD has the potential to prevent or reverse the long-term complications associated with ADT.
雄激素剥夺治疗（ADT）的显著副作用对生活质量（QoL）有重要影响。间歇性雄激素剥夺（IAD）在治疗周期之间交替使用雄激素阻断和治疗停止，从而允许激素恢复，从而潜在地提高耐受性和 QoL。
评估 IAD 在前列腺癌（PCa）治疗中的疗效和耐受性的现有证据，并评估其价值。
在过去 10 年中，使用“前列腺肿瘤”[MeSH]、间歇性雄激素抑制、间歇性激素剥夺、间歇性雄激素剥夺和间歇性激素治疗等术语，在 Medline 上搜索 IAD 在 PCa 中的关键 2/3 期临床试验。还包括在 2008-2009 年会议上报告的试验的摘要。
讨论了 19 项 2 期研究的数据，涉及治疗暂停/重新开始的前列腺特异性抗原值、治疗方案、周期长度、睾酮正常化和耐受性。结果数据很有希望：大多数试验报告在治疗中断期间 QoL 有所改善。八项比较 IAD 和持续雄激素剥夺（CAD）的 3 期试验的中期数据支持 2 期结果。IAD 在各种结局方面与 CAD 相当，包括生化进展、无进展生存期和总生存期。然而，在一项研究中，IAD 与 CAD 相比，3 年进展风险显著降低，并且具有耐受性优势，尤其是在性功能方面。还讨论了最有可能从 IAD 中受益的患者和预测反应不良的因素。
IAD 似乎与 CAD 一样有效，同时具有耐受性和 QoL 优势，特别是恢复性能力；然而，目前还没有足够的数据来确定 IAD 是否有可能预防或逆转与 ADT 相关的长期并发症。
