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: 10398005
• 负责人: SHALENDER BHASIN
• 金额: $ 72.19万
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10398005
• 关键词: Adverse event; Advocate; Aerobic; Affect; Affective; American; Androgens; Area; Attention; Biochemical; 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; Metastatic Prostate Cancer; Monitor; Moods; Oncologist; Oncology Group; Organ; Participant; Patient Self-Report; Patients; Personal Satisfaction; Physical Function; Placebo Control; 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; deprivation; disorder risk; editorial; efficacy evaluation; 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; performance based measurement; prostate cancer risk; prostate cancer survivors; 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.

总结 男性前列腺癌（PCa）患者生存率的显著改善将注意力集中在高水平的 性功能障碍、身体功能障碍和精力低下的患病率，这些都是导致 前列腺癌幸存者的次优健康相关生活质量（HRQOL）。这些疾病的病理生理学 前列腺癌幸存者的症状是多因素的，但雄激素缺乏是一种常见的，可治愈的 贡献者。在健康的性腺功能减退男性中，睾酮替代疗法（TRT）可改善这些症状， 这表明它也可能对患有睾丸激素缺乏症的PCa幸存者起作用。但由于 睾丸激素促进转移性前列腺癌的生长， TRT治疗前列腺癌幸存者。开放标签试验和回顾性分析报告了非常低的 接受根治性直肠癌切除术并接受TRT的男性的复发率，但安全性和 在该人群中的随机试验中评价了疗效。西南肿瘤组的病人 倡导者认为这是前列腺癌幸存者的一个高度优先的问题。 我们的主要目的是进行一项双盲、安慰剂对照、平行组、随机试验，以确定 睾酮替代治疗在改善雄激素男性性功能方面是否安全有效 缺乏症，因pT 2、N 0、M0、Gleason评分≤6分的疾病接受根治性乳腺癌切除术， 疾病复发的风险非常低。第二个目的是确定TRT是否改善肌肉质量， 力量，自我报告和基于表现的身体功能测量。第三个目标是 确定TRT对健康和情感，情绪，能量和生活质量的影响。试验将招募男性， 40岁或以上，因器官局限性前列腺癌（pT 2，N 0，M0）接受根治性前列腺切除术; Gleason评分≤6;治疗前PSA <10 ng/mL;和至少两种情况下检测不到PSA（<0.1 ng/mL） 根治性前列腺切除术后3年;有性功能障碍、疲劳或身体功能障碍症状的患者; 和明确低总（两个早晨的平均水平<275 ng/dL）或游离睾酮（<60 pg/mL）水平。参与者将随机接受安慰剂或睾酮凝胶12周。变化 性活动，性欲，勃起功能，性困扰，性生活质量，瘦体重，肌肉 将在基线、第6周和第12周评价力量、身体功能、情感平衡和能量。我们 将监测红细胞压积、PSA和生化复发，定义为”PSA ≥0.2 ng/mL， 水平≥0.2 ng/mL”。仔细选择复发风险极低的受试者，严格的安全性监测， 预先规定的停止规则和独立DSMB的监督将最大限度地降低风险。广泛的初步 数据支持这项试验的可行性。随机试验设计，多学科团队，仔细关注 统计功效和选择有明显低睾酮症状的男性将确保有效性 评估睾酮治疗在这一需要帮助的患者人群中的有效性和安全性。