Columbia University Medical Center, New York, New York.
Fred Hutchinson Cancer Research Center, Seattle, Washington.
JAMA Oncol. 2016 Apr;2(4):453-61. doi: 10.1001/jamaoncol.2015.4655.
Although intermittent androgen-deprivation therapy (ADT) has not been associated with better overall survival in prostate cancer (PC), it has the potential for lower adverse effects. To our knowledge, the incidence of long-term adverse health events has not been reported.
To examine long-term late events in elderly patients randomized to intermittent or continuous ADT to determine whether late cardiovascular and endocrine events would be lower in patients treated with intermittent ADT.
DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of a multicenter clinical trial using linkage between patient data from S9346, a randomized SWOG trial of intermittent vs continuous ADT in men with metastatic PC, and corresponding Medicare claims.
Intermittent or continuous ADT.
The main outcome was to identify long-term adverse health events by treatment arm. Patients were classified as having an adverse health event if they had any hospital claim--or at least 2 physician or outpatient claims at least 30 days apart--for any of the following diagnoses: ischemic and thrombotic events, endocrine events, sexual dysfunction, dementia, and depression. To incorporate time from beginning of observation through evidence of an event, we determined the cumulative incidence of each event. Competing risks Cox regression was used, adjusting for covariates.
In total, 1134 eligible US-based male patients with metastatic PC were randomized to continuous vs intermittent ADT in the S9346 trial. A total of 636 of trial participants (56%) had at least 1 year of continuous Medicare parts A and B coverage and no health maintenance organization participation. The median age was 71.3 years. The most common long-term events were hypercholesterolemia (31%) and osteoporosis (19%). The 10-year cumulative incidence of ischemic and thrombotic events differed by arm; 24% for continuous and 33%for intermittent ADT (hazard ratio, 0.69; P = .02). There were no statistically significant differences by arm in any other adverse health events.
Contrary to our hypothesis that intermittent ADT would reduce long-term health-related events compared with continuous ADT, we found that older men assigned to intermittent ADT had no apparent reduction in bone, endocrine, or cognitive events and an increased incidence of ischemic and thrombotic events.
clinicaltrials.gov Identifier: NCT00002651.
尽管间歇性雄激素剥夺疗法（ADT）与前列腺癌（PC）的总生存改善无关，但它具有降低不良反应的潜力。据我们所知，尚未报道长期不良健康事件的发生率。
检查接受间歇性或连续性 ADT 治疗的老年患者的长期晚期事件，以确定间歇性 ADT 治疗的患者是否会出现较低的晚期心血管和内分泌事件。
设计、地点和参与者：这是一项多中心临床试验的二次分析，该试验使用 S9346 患者数据的链接，该试验是一项比较转移性 PC 男性间歇性与连续性 ADT 的 SWOG 随机试验，以及相应的医疗保险索赔。
间歇性或连续性 ADT。
主要结果是通过治疗臂识别长期不良健康事件。如果患者有任何住院索赔-或至少 2 次医生或门诊索赔，间隔至少 30 天-任何以下诊断之一，则将其归类为出现不良健康事件：缺血和血栓事件、内分泌事件、性功能障碍、痴呆和抑郁。为了将观察开始时的时间纳入其中，我们确定了每个事件的累积发生率。使用竞争风险 Cox 回归，调整协变量。
共有 1134 名符合条件的美国转移性 PC 男性患者在 S9346 试验中被随机分配至连续或间歇性 ADT。共有 636 名试验参与者（56%）至少有 1 年的连续医疗保险 A 部分和 B 部分覆盖，并且没有健康维护组织参与。中位年龄为 71.3 岁。最常见的长期事件是高胆固醇血症（31%）和骨质疏松症（19%）。缺血和血栓形成事件的 10 年累积发生率因手臂而异；连续组为 24%，间歇性 ADT 组为 33%（风险比，0.69；P = .02）。手臂之间在任何其他不良健康事件方面均无统计学差异。
与我们的假设相反，即间歇性 ADT 与连续 ADT 相比会降低长期与健康相关的事件，我们发现，与间歇性 ADT 相比，被分配到间歇性 ADT 的老年男性在骨骼、内分泌或认知事件方面没有明显减少，而缺血性和血栓性事件的发生率增加。
clinicaltrials.gov 标识符：NCT00002651。
