Improving Quality of Life of Prostate Cancer Survivors with Androgen Deficiency

改善雄激素缺乏的前列腺癌幸存者的生活质量

• 批准号: 9750591
• 负责人: SHALENDER BHASIN
• 金额: $ 75.47万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750591
• 关键词: Adverse event; Advocate; Aerobic; Affect; Affective; American; Androgens; Area; Attention; Biochemical; Cancer Survivor; Cardiovascular system; Clinical Trials Data Monitoring Committees; Complex; Data; Diagnosis; Disease; Distress; Double-Blind Method; Elements; Enrollment; Equilibrium; Evaluation; Fatigue; Fright; Functional disorder; Gel; Gene Expression; Gleason Grade for Prostate Cancer; Growth; Hematocrit procedure; High Prevalence; Letters; Lipids; Localized Disease; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Metastatic Prostate Cancer; Monitor; Moods; Oncologist; Oncology Group; Organ; Participant; Patient Self-Report; Patients; Performance; Personal Satisfaction; Physical Function; Placebos; Population; Prostate; Prostate specific antigen measurement; Published Comment; Quality of life; Radical Prostatectomy; Randomized; Recommendation; Recurrence; Reporting; Research; Risk; Safety; Sex Behavior; Sex Functioning; Sexual Dysfunction; Specific qualifier value; Structure; Subjects Selections; Survivors; Symptoms; Testosterone; Urologist; VO2max; androgen sensitive; base; deprivation; disorder risk; editorial; efficacy trial; epidemiology study; feasibility trial; health related quality of life; improved; instrument; lean body mass; men; multidisciplinary; muscle form; muscle strength; open label; patient population; prostate cancer risk; randomized trial; risk minimization; survivorship; symptom treatment; symptomatic improvement; testosterone replacement therapy; trial design

SUMMARY Substantial improvement in survival in men with prostate cancer (PCa) has focused attention on the high prevalence of sexual dysfunction, physical dysfunction, and low energy, which are important contributors to suboptimal health-related quality of life (HRQOL) in prostate cancer survivors. The pathophysiology of these symptoms in prostate cancer survivors is multifactorial, but androgen deficiency is a frequent, remediable contributor. In healthy hypogonadal men, testosterone replacement therapy (TRT) improves these symptoms, suggesting that it also might do so for survivors of PCa who have testosterone deficiency. However, because testosterone promotes the growth of metastatic prostate cancer, there has been concern about administering TRT to prostate cancer survivors. Open label trials and retrospective analyses have reported very low recurrence rates in men who have undergone radical prostatectomy and received TRT, but neither safety nor efficacy have been evaluated in a randomized trial in this population. The South West Oncology Group patient advocates have deemed this a high priority question for prostate cancer survivors. Our primary aim is to conduct a double-blind, placebo-controlled, parallel-group, randomized trial to determine whether testosterone replacement is safe and efficacious in improving sexual function in men with androgen deficiency, who have undergone radical prostatectomy for pT2,N0,M0, Gleason score ≤6 disease and are at very low risk of disease recurrence. A secondary aim is to determine whether TRT improves muscle mass and strength, and self reported and performance-based measures of physical function. The third objective is to determine the effects of TRT on wellbeing and affect, mood, energy, and quality of life. The trial will enroll men, 40 years or older, who have undergone radical prostatectomy for organ-localized prostate cancer (pT2,N0,M0); with Gleason score ≤6; pre-treatment PSA <10 ng/mL; and undetectable PSA (<0.1 ng/mL) for at least two years after radical prostatectomy; who have symptoms of sexual dysfunction, fatigue, or physical dysfunction; and who have unequivocally low total (average of two morning levels <275 ng/dL) or free testosterone (<60 pg/mL) levels. Participants will be randomized to receive placebo or testosterone gel for 12 weeks. Changes in sexual activity, sexual desire, erectile function, sexual distress, sexual life quality, lean body mass, muscle strength, physical function, affectivity balance, and energy will be evaluated at baseline, 6 and 12 weeks. We will monitor hematocrit, PSA, and biochemical recurrence, defined as” PSA of ≥0.2 ng/mL with a confirmatory level of ≥0.2 ng/mL”. Careful selection of subjects with very low risk of recurrence, rigorous safety monitoring, pre-specified stopping rules, and oversight by an independent DSMB will minimize risks. Extensive preliminary data support the feasibility of this trial. Randomized trial design, a multidisciplinary team, careful attention to statistical power, and selection of symptomatic men with unequivocally low testosterone will insure the validity of the assessment of efficacy and safety of testosterone therapy in this needy patient population.

概括 前列腺癌（PCA）男性生存的大幅改善已将注意力集中在高中 性功能障碍，身体功能障碍和低能量的患病率是重要的原因 前列腺癌存活中与健康相关的生活质量（HRQOL）。这些的病理生理学 前列腺癌存活中的症状是多因素的，但雄激素缺乏症通常是一种可补充的 贡献者。在健康的性腹膜男性中，睾丸激素替代疗法（TRT）改善了这些症状， 这也可能是为了生存具有睾丸激素缺乏症的PCA的生存。但是，因为 睾丸激素促进转移性前列腺癌的生长，一直担心管理 TRT到前列腺癌的存活。开放标签试验和回顾性分析报告非常低 进行了根治性前列腺切除术并接受TRT的男性的复发率，但既不安全也不 在该人群中的一项随机试验中已经评估了功效。西南肿瘤学组患者 拥护者认为这是前列腺癌存活的高优先问题。 我们的主要目的是进行双盲，安慰剂对照，平行组，随机试验以确定 睾丸激素的替代是否可以安全有效地改善雄激素男性的性功能 缺乏症，对PT2，N0，M0进行了根治性前列腺切除术，格里森评分≤6疾病，并且处于 疾病复发的风险非常低。次要目的是确定TRT是否改善了肌肉质量和 力量，自我报告和基于绩效的身体功能测量。第三个目标是 确定TRT对福祉和影响，情绪，能量和生活质量的影响。审判将注册男人， 40岁或以上，他们接受了组织重新定位的前列腺癌（PT2，N0，M0）的根治性前列腺切除术； 格里森评分≤6;预处理PSA <10 ng/ml;至少两个 根治性前列腺切除术几年；患有性功能障碍，疲劳或身体功能障碍的症状； 以及明确较低的总（平均两个早晨水平<275 ng/dl）或免费睾丸激素（<60） pg/ml）水平。参与者将被随机接收安慰剂或睾丸激素凝胶12周。变更 性活动，性欲，勃起功能，性困扰，性生活质量，瘦身质量，肌肉 强度，身体机能，情感平衡和能量将在基线，6和12周进行评估。我们 将监测血细胞比容，PSA和生化复发，定义为“ PSA”≥0.2ng/ml，并确认为 ≥0.2ng/ml的水平。 预先指定的停止规则，而独立DSMB的监督将最大程度地降低风险。广泛的初步 数据支持该试验的可行性。随机试验设计，一个多学科团队，仔细注意 统计能力和症状性男性的选择明确睾丸激素将确保有效性 在这个有需要的患者人群中评估睾丸激素治疗的效率和安全性的评估。