Département d'Urologie, Clinique Mutualiste de la Loire, Saint-Etienne, France.
BJU Int. 2012 Nov;110(9):1262-9. doi: 10.1111/j.1464-410X.2012.11120.x. Epub 2012 Apr 13.
Study Type - Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Intermittent androgen deprivation therapy (ADT) involves cycling ADT, allowing hormonal recovery during off-treatment periods. This could lead to a better quality of life during off-treatment periods and could delay progression to castration resistance. Safety and feasibility of intermittent ADT have been shown but tolerability and health-related quality of life improvement have been suggested but questioned by others. Results from randomized trials, including relapsing or mixed populations, have suggested intermittent ADT to be as effective as continuous ADT. In this study of only metastatic patients, no statistical difference in either overall survival or progression-free survival was shown between intermittent and continuous ADT and suggests that intermittent might be as safe as continuous castration. It could be an option in highly responding and well-informed metastatic patients even if no clear benefit in health-related quality of life was shown. This intermittent modality could be of interest in metastatic patients with significant treatment-induced side-effects.
• To compare intermittent androgen deprivation therapy (ADT) and continuous ADT after 6 months of induction of ADT in patients with metastatic prostate cancer (PCa).
• This is an open-label randomized multi-centre study conducted in 58 centres in Europe. • Patients with metastatic PCa and prostate-specific antigen (PSA) level >20 ng/mL at selection were randomized after 6 months of induction of ADT (leuprorelin and flutamide) if PSA level had decreased below 4 ng/mL. • Patients received either continuous or intermittent ADT. All patients were treated until signs of disease progression under treatment or until study end with a monthly central PSA determination and follow-up visits were performed every 3 months. • The primary endpoint was overall survival. Secondary endpoints included progression-free survival, health-related quality of life (QLQ C30 questionnaire) and safety criteria.
• Of 383 selected patients, 173 had a PSA level below 4 ng/mL after 6 months of induction of ADT and were randomized. Median overall survival (52 vs 42 months, P= 0.75) and median progression-free survival (15.1 vs 20.7 months, P= 0.74) were not significantly different between continuous and intermittent ADT. • Although some differences in quality of life were observed, most of the functional and symptom scales showed no significant difference between the two groups. • Significantly fewer treatment-emergent adverse events occurred in the intermittent group (P= 0.042), with the incidence of headache and hot flushes also lower.
• This first randomized trial comparing continuous with intermittent ADT in metastatic PCa suggests that intermittent ADT might be as safe as continuous ADT. • It could be an option in highly responding and well-informed patients even if no clear benefit in health-related quality of life was shown.
研究类型 - 治疗（RCT）证据水平 1b。关于这个主题已经知道了什么？研究增加了什么？间歇性雄激素剥夺疗法（ADT）涉及 ADT 循环，允许在治疗间歇期恢复激素水平。这可能会在治疗间歇期提高生活质量，并可能延迟向去势抵抗进展。间歇性 ADT 的安全性和可行性已经得到证实，但其他人对其耐受性和健康相关生活质量的改善提出了质疑。包括复发或混合人群在内的随机试验结果表明，间歇性 ADT 与连续 ADT 同样有效。在这项仅针对转移性患者的研究中，连续和间歇性 ADT 之间在总生存或无进展生存方面均未显示出统计学差异，表明间歇性 ADT 与连续去势一样安全。对于反应良好且知情的转移性患者，即使没有显示出健康相关生活质量的明显获益，它也可能是一种选择。对于有显著治疗相关副作用的转移性患者，这种间歇性治疗模式可能具有吸引力。
比较转移性前列腺癌（PCa）患者在接受 6 个月 ADT 诱导后接受间歇性和连续 ADT。
这是一项在欧洲 58 个中心进行的开放性、随机、多中心研究。入选时选择具有转移性 PCa 和前列腺特异性抗原（PSA）水平>20ng/mL 的患者，在接受 ADT（亮丙瑞林和氟他胺）诱导 6 个月后，如果 PSA 水平降至<4ng/mL，患者将进行随机分组。患者接受连续或间歇性 ADT。所有患者均接受治疗，直至治疗期间出现疾病进展迹象或研究结束（每月进行中央 PSA 测定并每 3 个月进行一次随访）。主要终点为总生存。次要终点包括无进展生存、健康相关生活质量（QLQ C30 问卷）和安全性标准。
在 383 名入选的患者中，有 173 名在接受 ADT 诱导 6 个月后 PSA 水平<4ng/mL，进行了随机分组。连续和间歇性 ADT 之间的中位总生存（52 个月与 42 个月，P=0.75）和中位无进展生存（15.1 个月与 20.7 个月，P=0.74）无显著差异。虽然观察到生活质量的一些差异，但大多数功能和症状量表在两组之间没有显著差异。间歇性组发生的治疗相关不良事件明显较少（P=0.042），头痛和热潮红的发生率也较低。
这是第一项比较转移性 PCa 中连续和间歇性 ADT 的随机试验，表明间歇性 ADT 可能与连续 ADT 一样安全。对于反应良好且知情的患者，即使没有显示出健康相关生活质量的明显获益，它也可能是一种选择。
