Calais da Silva Fernando E C, Bono Aldo V, Whelan Peter, Brausi Maurizio, Marques Queimadelos Anton, Martin Jose A Portillo, Kirkali Ziya, Calais da Silva Fernando M V, Robertson Chris
Department of Urology, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.
Eur Urol. 2009 Jun;55(6):1269-77. doi: 10.1016/j.eururo.2009.02.016. Epub 2009 Feb 21.
Few randomised studies have compared intermittent hormonal therapy (IHT) with continuous therapy for the treatment of advanced prostate cancer (PCa).
To determine whether intermittent therapy is associated with a shorter time to progression.
DESIGN, SETTING, AND PARTICIPANTS: 766 patients with locally advanced or metastatic PCa received a 3-mo induction treatment. The 626 patients whose prostate-specific antigen (PSA) level decreased to <4 ng/ml or to 80% below the initial value were randomised.
Patients received cyproterone acetate (CPA) 200mg for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH) analogue plus 200mg of CPA daily during induction. Patients randomised to the intermittent arm ceased treatment, while those randomised to the continuous arm received 200mg of CPA daily plus an LHRH analogue.
Primary outcome measurement was time to subjective or objective progression. Secondary outcomes were survival and quality of life (QoL). Time off therapy in the intermittent arm was also recorded.
127 patients from the intermittent arm and 107 patients from the continuous arm progressed, with a hazard ratio (HR) of 0.81 (95% confidence interval [CI]: 0.63-1.05, p=0.11). There was no difference in survival, with an HR of 0.99 (95% CI: 0.80-1.23) and 170 deaths in the intermittent arm and 169 deaths in the continuous arm. The greater number of cancer deaths in the intermittent treatment arm (106 vs 84) was balanced by a greater number of cardiovascular deaths in the continuous arm (52 vs 41). Side-effects were more pronounced in the continuous arm. Men treated with intermittent therapy reported better sexual function. Median time off therapy for the intermittent patients was 52 wk (95% CI: 39.4-65.7).
IHT should be considered for use in routine practice because it is associated with no reduction in survival, no clinically meaningful impairment in QoL, better sexual activity, and considerable economic benefit to the individual and the community.
很少有随机研究比较间歇性激素疗法（IHT）与持续性疗法治疗晚期前列腺癌（PCa）的效果。
确定间歇性疗法是否与较短的疾病进展时间相关。
设计、机构和参与者：766例局部晚期或转移性PCa患者接受了为期3个月的诱导治疗。626例前列腺特异性抗原（PSA）水平降至<4 ng/ml或降至初始值以下80%的患者被随机分组。
患者在诱导期接受醋酸环丙孕酮（CPA）200mg，持续2周，然后每月注射一次促黄体生成素释放激素（LHRH）类似物，并每日服用200mg CPA。随机分配到间歇性治疗组的患者停止治疗，而随机分配到持续性治疗组的患者每日接受200mg CPA加一种LHRH类似物。
主要结局指标是主观或客观进展时间。次要结局指标是生存率和生活质量（QoL）。还记录了间歇性治疗组的停药时间。
间歇性治疗组127例患者和持续性治疗组107例患者出现疾病进展，风险比（HR）为0.81（95%置信区间[CI]：0.63 - 1.05，p = 0.11）。生存率无差异，HR为0.99（95% CI：0.80 - 1.23），间歇性治疗组有170例死亡，持续性治疗组有169例死亡。间歇性治疗组癌症死亡人数较多（106例对84例），但持续性治疗组心血管死亡人数较多（52例对41例），二者相互抵消。持续性治疗组的副作用更明显。接受间歇性治疗的男性性功能报告较好。间歇性治疗患者的中位停药时间为52周（95% CI：39.4 - 65.7）。
IHT应被考虑用于常规治疗，因为它不会降低生存率，不会对生活质量造成有临床意义的损害，能改善性功能，并且对个人和社会有可观的经济效益。
