间歇性雄激素抑制:晚期前列腺癌治疗及改善生活质量的又一选择

背景持续性雄激素抑制(continuous androgen suppression,CAS)是目前晚期前列腺癌内分泌治疗的金标准.CAS不仅可能导致前列腺癌的雄激素依赖状态迅速丧失,使预后更差,而且可能导致生活质量下降,以及与治疗相关的副作用及费用明显增加.近年来的一些实验研究及临床观察性试验显示,间歇性雄激素抑制(intermiRent androgen suppression,IAS)可能避免或至少能够减少以上缺点.但是目前仍有争议.目的回顾关于LAS的实验及临床研究结果,明确IAS是否为晚期前列腺癌的较为理想的治疗方式.研究选择选择关于IAS的文献,不排除其是否为随机、盲法等论证推荐的文章.数据来源进行全面的检索,检索手段包括电子检索、手工检索及个人通信等.数据提取对检索到的IAS及CAS研究文章中相关信息进行综述.主要观察指标IAS与CAS比较,可能延缓前列腺癌进展为雄激素非依赖状态,延长生存期,提高生活质量,减少副作用和治疗费用.结果实验研究提示,周期性地进行IAS可能恢复肿瘤细胞的凋亡能力,从而延缓雄激素非依赖状态的产生;临床观察也提示IAS可能能够延缓前列腺癌进展为雄激素非依赖状态,延长生存期,提高生活质量(恢复性欲、性功能等)以及减少治疗相关的费用和副作用.2个正在进行的随机临床试验的中期分析也证实IAS较之于CAS 3年进展率要低,而生活质量尤其是性功能明显改善.结论越来越多的证据表明IAS治疗晚期前列腺癌是可行的,可能是比CAS更为理想的治疗方式.在推荐其作为晚期前列腺癌的常规甚至标准治疗方式之前,有必要获取来自随机临床试验乃至系统综述的证据进一步证实其可行性及优越性.

Intermittent androgen suppression:another optional modality for treating advanced prostate cancer and improving quality of life

BACKGROUND: Continuous androgen suppression(CAS) is currently the gold standard of hormone therapy for advanced prostate cancer. However, it may cause rapid loss of androgen dependence, which results in a worse prognosis,impair quality of life, and increase treatment-related adverse events and costs adverse events. In recent years, some laboratory experiments and observational clinical studies have shown that intermittent androgen suppression(IAS) may avoid or at least reduce these disadvantages, but disputes still exist.OBJECTIVE: To review the experimental and clinical results of IAS studies,and to verify whether lAS is an ideal therapyfor advanced prostate cancer.STUDY SELECTION: References concerning IAS were consulted, no matter the recommended articles based on randomized or blind proofs. DATA SOURCES: A comprehensive search. The search tools include electronic search, manual search, and personal communications.DATA EXTRACTION: The related information on the searched articles concerning IAS and CAS were summarized.MAIN OUTCOME MEASURES: Androgen-independent progression, survival, quality of life, treatment-related costs and adverse events.RESULTS: Experimental studies have indicated that periodically sdministered IAS may restore the apoptosis of tumor cells, and subsequently delay the progression to an androgen-independent state. Clinical observations suggested that IAS may benefit patients with: delayed androgen-independent progression; prolong survival time; improve quality of life(regaining libido and potency); and reduce treatment-related costs and adverse events. Furthermore,interim analysis of two ongoing randomized clinical trials(RCTs) suggested that, compared with CAS, patients treated with IAS have an improvement in quality of life, especially in sexual activity, and a significantly decrease in 3-year progression rate.CONCLUSION: More evidences have suggested that IAS be a feasible treatment modality for advanced prostate cancer. It may be a promising alternative to CAS. However, further evidences from RCTs or even a systematic review are needed before recommending IAS as routine or standard therapy.