间歇性与连续性雄激素剥夺疗法治疗晚期前列腺癌的严重毒性风险：基于人群的研究。
Risks of Serious Toxicities from Intermittent versus Continuous Androgen Deprivation Therapy for Advanced Prostate Cancer: A Population Based Study.
机构信息
Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, D.C..
National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
出版信息
J Urol. 2017 May;197(5):1251-1257. doi: 10.1016/j.juro.2016.12.022. Epub 2016 Dec 16.
PURPOSE
Randomized trials have shown that intermittent androgen deprivation therapy for patients with advanced prostate cancer may improve sexual and physical functioning compared to continuous androgen deprivation therapy without compromising survival. To our knowledge it is unknown whether intermittent androgen deprivation therapy alters the risk of serious toxicities associated with continuous androgen deprivation therapy.
MATERIALS AND METHODS
We performed a population based cohort study of 9,772 men 66 years old or older who were diagnosed with advanced prostate cancer from 2002 to 2011 and treated with androgen deprivation therapy. Intermittent androgen deprivation therapy was defined as a single 90-day interval between 2 androgen deprivation therapy sessions during which patients visited their physicians or underwent prostate specific antigen testing. Outcomes included acute myocardial infarction, stroke, heart failure, type 2 diabetes and fracture. We used Cox proportional hazard models to estimate the HRs of the comparative risk of serious toxicities between intermittent and continuous androgen deprivation therapy.
RESULTS
A total of 2,113 (22%), 769 (9%) and 899 men (9%) had a new cardiovascular event, diabetes or fracture, respectively, within 5 years of starting androgen deprivation therapy. Compared to the continuous androgen deprivation therapy group, the intermittent therapy group was at lower risk for serious cardiovascular events (HR 0.64, 95% CI 0.53-0.77), particularly in reducing the risk of heart failure (HR 0.62, 95% CI 0.49-0.78) and fracture (HR 0.52, 95% CI 0.38-0.70, each p <0.0001).
CONCLUSIONS
Intermittent androgen deprivation therapy was associated with a lower risk of heart failure and fracture compared to continuous androgen deprivation therapy. This raises toxicity concerns for continuous relative to intermittent therapy and suggests that intermittent androgen deprivation therapy may represent a safer therapeutic choice in elderly men with advanced prostate cancer.
目的
随机试验表明，与连续雄激素剥夺疗法相比，晚期前列腺癌患者的间歇性雄激素剥夺疗法可能改善性功能和身体机能，而不会影响生存。据我们所知，目前尚不清楚间歇性雄激素剥夺疗法是否会改变与连续雄激素剥夺疗法相关的严重毒性的风险。
材料和方法
我们对 2002 年至 2011 年间被诊断为晚期前列腺癌且接受雄激素剥夺疗法治疗的 9772 名 66 岁或以上的男性进行了基于人群的队列研究。间歇性雄激素剥夺疗法定义为在两次雄激素剥夺治疗期间，患者就诊或进行前列腺特异抗原检测时，单次 90 天的间隔。结局包括急性心肌梗死、中风、心力衰竭、2 型糖尿病和骨折。我们使用 Cox 比例风险模型估计间歇性和连续雄激素剥夺疗法之间严重毒性的相对风险比。
结果
在开始雄激素剥夺治疗后 5 年内，共有 2113 名（22%）、769 名（9%）和 899 名（9%）男性分别发生新的心血管事件、糖尿病或骨折。与连续雄激素剥夺治疗组相比，间歇性治疗组严重心血管事件的风险较低（风险比 0.64，95%置信区间 0.53-0.77），特别是心力衰竭（风险比 0.62，95%置信区间 0.49-0.78）和骨折（风险比 0.52，95%置信区间 0.38-0.70，均<0.0001）的风险降低。
结论
与连续雄激素剥夺疗法相比，间歇性雄激素剥夺疗法与心力衰竭和骨折风险降低相关。这引发了对连续疗法相对间歇性疗法的毒性问题，并表明间歇性雄激素剥夺疗法可能是老年晚期前列腺癌男性更安全的治疗选择。
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