Neoadjuvant Exercise Therapy in Prostate Cancer: A Phase 1, Decentralized Nonrandomized ControlledTrial.

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology Jama Oncology Pub Date : 2024-09-01 DOI:10.1001/jamaoncol.2024.2156

Lee W Jones, Chaya S Moskowitz, Catherine P Lee, Gina A Fickera, Su S Chun, Meghan G Michalski, Kurtis Stoeckel, Whitney P Underwood, Jessica A Lavery, Umeshkumar Bhanot, Irina Linkov, Chau T Dang, Behfar Ehdaie, Vincent P Laudone, James A Eastham, Anne Collins, Patricia T Sheerin, Lydia Y Liu, Stefan E Eng, Paul C Boutros

{"title":"Neoadjuvant Exercise Therapy in Prostate Cancer: A Phase 1, Decentralized Nonrandomized ControlledTrial.","authors":"Lee W Jones, Chaya S Moskowitz, Catherine P Lee, Gina A Fickera, Su S Chun, Meghan G Michalski, Kurtis Stoeckel, Whitney P Underwood, Jessica A Lavery, Umeshkumar Bhanot, Irina Linkov, Chau T Dang, Behfar Ehdaie, Vincent P Laudone, James A Eastham, Anne Collins, Patricia T Sheerin, Lydia Y Liu, Stefan E Eng, Paul C Boutros","doi":"10.1001/jamaoncol.2024.2156","DOIUrl":null,"url":null,"abstract":"Importance: Observational data have shown that postdiagnosis exercise is associated with reduced risk of prostate cancer death. The feasibility and tumor biological activity of exercise therapy is not known.Objective: To identify recommended phase 2 dose of exercise therapy for patients with prostate cancer.Design, setting, and participants: This single-center, phase 1a dose-finding trial was conducted at a tertiary cancer center using a patientcentric, decentralized platform and included 53 inactive men with treatment-naive localized prostate cancer scheduled to undergo surgical resection between June 2019 and January 2023. Data were analyzed in June 2024.Intervention: Six escalated exercise therapy dose levels ranging from 90 to 450 minutes per week of individualized, moderate-intensity treadmill walking, allocated using adaptive continual reassessment. All exercise therapy sessions were conducted remotely with real-time monitoring.Main outcomes and measures: Feasibility was evaluated by relative exercise dose intensity (REDI). A dose level was considered feasible if 70% or more of patients achieved an REDI of 75% or greater. Activity end points were changes in tumor cell proliferation (Ki67) and plasma prostate-specific antigen levels between pretreatment and postintervention. Safety and changes in patient physiology were also assessed.Results: A total of 53 men were enrolled (median [IQR] age, 61 [56-66] years). All dose levels were feasible (≥75% REDI). The mean (95% CI) changes in Ki67 were 5.0% (-4.3% to 14.0%) for 90 minutes per week, 2.4% (-1.3% to 6.2%) for 150 minutes per week, -1.3% (-5.8% to 3.3%) for 225 minutes per week, -0.2% (-4.0% to 3.7%) for 300 minutes per week, -2.6% (-9.2% to 4.1%) for 375 minutes per week, and 2.2% (-0.8% to 5.1%) for 450 minutes per week. Changes in prostate-specific antigen levels were 1.0 ng/mL (-1.8 to 3.8) for 90 minutes per week, 0.2 ng/mL (-1.1 to 1.5) for 150 minutes per week, -0.5 ng/mL (-1.2 to 0.3) for 225 minutes per week, -0.2 (-1.7 to 1.3) for 300 minutes per week, -0.7 ng/mL (-1.7 to 0.4) for 375 minutes per week, and -0.9 ng/mL (-2.4 to 0.7) for 450 minutes per week. No serious adverse events were observed. Overall, 225 minutes per week (approximately 45 minutes per treatment at 5 times weekly) was selected as the recommended phase 2 dose.Conclusions and relevance: The results of this nonrandomized clinical trial suggest that neoadjuvant exercise therapy is feasible and safe with promising activity in localized prostate cancer.Trial registration: ClinicalTrials.gov Identifier: NCT03813615.","PeriodicalId":48661,"journal":{"name":"Jama Oncology","volume":null,"pages":null},"PeriodicalIF":28.4000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11258635/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Jama Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1001/jamaoncol.2024.2156","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}

引用次数: 0

Abstract

Importance: Observational data have shown that postdiagnosis exercise is associated with reduced risk of prostate cancer death. The feasibility and tumor biological activity of exercise therapy is not known.

Objective: To identify recommended phase 2 dose of exercise therapy for patients with prostate cancer.

Design, setting, and participants: This single-center, phase 1a dose-finding trial was conducted at a tertiary cancer center using a patientcentric, decentralized platform and included 53 inactive men with treatment-naive localized prostate cancer scheduled to undergo surgical resection between June 2019 and January 2023. Data were analyzed in June 2024.

Intervention: Six escalated exercise therapy dose levels ranging from 90 to 450 minutes per week of individualized, moderate-intensity treadmill walking, allocated using adaptive continual reassessment. All exercise therapy sessions were conducted remotely with real-time monitoring.

Main outcomes and measures: Feasibility was evaluated by relative exercise dose intensity (REDI). A dose level was considered feasible if 70% or more of patients achieved an REDI of 75% or greater. Activity end points were changes in tumor cell proliferation (Ki67) and plasma prostate-specific antigen levels between pretreatment and postintervention. Safety and changes in patient physiology were also assessed.

Results: A total of 53 men were enrolled (median [IQR] age, 61 [56-66] years). All dose levels were feasible (≥75% REDI). The mean (95% CI) changes in Ki67 were 5.0% (-4.3% to 14.0%) for 90 minutes per week, 2.4% (-1.3% to 6.2%) for 150 minutes per week, -1.3% (-5.8% to 3.3%) for 225 minutes per week, -0.2% (-4.0% to 3.7%) for 300 minutes per week, -2.6% (-9.2% to 4.1%) for 375 minutes per week, and 2.2% (-0.8% to 5.1%) for 450 minutes per week. Changes in prostate-specific antigen levels were 1.0 ng/mL (-1.8 to 3.8) for 90 minutes per week, 0.2 ng/mL (-1.1 to 1.5) for 150 minutes per week, -0.5 ng/mL (-1.2 to 0.3) for 225 minutes per week, -0.2 (-1.7 to 1.3) for 300 minutes per week, -0.7 ng/mL (-1.7 to 0.4) for 375 minutes per week, and -0.9 ng/mL (-2.4 to 0.7) for 450 minutes per week. No serious adverse events were observed. Overall, 225 minutes per week (approximately 45 minutes per treatment at 5 times weekly) was selected as the recommended phase 2 dose.

Conclusions and relevance: The results of this nonrandomized clinical trial suggest that neoadjuvant exercise therapy is feasible and safe with promising activity in localized prostate cancer.

Trial registration: ClinicalTrials.gov Identifier: NCT03813615.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

前列腺癌新辅助运动疗法：一期分散非随机对照试验》。

重要性：观察性数据显示，确诊后运动与降低前列腺癌死亡风险有关。运动疗法的可行性和肿瘤生物学活性尚不清楚：目的：确定前列腺癌患者运动疗法第二阶段的推荐剂量：这项单中心 1a 期剂量摸底试验在一家三级癌症中心进行，采用以患者为中心的分散式平台，纳入了 53 名计划在 2019 年 6 月至 2023 年 1 月期间接受手术切除的、未经治疗的局部前列腺癌非活动男性患者。数据于 2024 年 6 月进行分析：干预措施：采用适应性持续再评估方法分配六个升级的运动疗法剂量级别，从每周 90 分钟到 450 分钟不等的个性化中等强度跑步机步行。所有运动疗法疗程均在实时监控下远程进行：通过相对运动剂量强度（REDI）评估可行性。如果 70% 或更多的患者达到 75% 或更高的 REDI，则该剂量水平被认为是可行的。活动终点为干预前与干预后肿瘤细胞增殖（Ki67）和血浆前列腺特异性抗原水平的变化。此外，还对安全性和患者生理变化进行了评估：共有 53 名男性患者（中位数[IQR]年龄为 61 [56-66] 岁）接受了治疗。所有剂量水平均可行（≥75% REDI）。每周 90 分钟的 Ki67 平均变化率（95% CI）为 5.0%（-4.3% 至 14.0%），每周 150 分钟的 Ki67 平均变化率为 2.4%（-1.3% 至 6.2%），每周 225 分钟的 Ki67 平均变化率为-1.3%（-5.8% 至 3.3%），每周 300 分钟的 Ki67 平均变化率为-0.2%（-4.0% 至 3.7%），每周 375 分钟的 Ki67 平均变化率为-2.6%（-9.2% 至 4.1%），每周 450 分钟的 Ki67 平均变化率为 2.2%（-0.8% 至 5.1%）。每周 90 分钟的前列腺特异性抗原水平变化为 1.0 纳克/毫升（-1.8 至 3.8），每周 150 分钟的变化为 0.2 纳克/毫升（-1.1 至 1.5），每周 225 分钟的变化为-0.5 纳克/毫升（-1.2 至 0.3）。每周 225 分钟为-0.5 毫微克/毫升（-1.2 至 0.3 毫微克/毫升），每周 300 分钟为-0.2 毫微克/毫升（-1.7 至 1.3 毫微克/毫升），每周 375 分钟为-0.7 毫微克/毫升（-1.7 至 0.4 毫微克/毫升），每周 450 分钟为-0.9 毫微克/毫升（-2.4 至 0.7 毫微克/毫升）。未观察到严重不良事件。总体而言，第 2 阶段的推荐剂量为每周 225 分钟（每次治疗约 5 分钟，每周 5 次）：这项非随机临床试验的结果表明，新辅助运动疗法是可行且安全的，对局部前列腺癌具有良好的疗效：试验注册：ClinicalTrials.gov Identifier：NCT03813615。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Jama Oncology Medicine-Oncology

CiteScore

37.50

自引率

1.80%

发文量

423

期刊介绍： At JAMA Oncology, our primary goal is to contribute to the advancement of oncology research and enhance patient care. As a leading journal in the field, we strive to publish influential original research, opinions, and reviews that push the boundaries of oncology science. Our mission is to serve as the definitive resource for scientists, clinicians, and trainees in oncology globally. Through our innovative and timely scientific and educational content, we aim to provide a comprehensive understanding of cancer pathogenesis and the latest treatment advancements to our readers. We are dedicated to effectively disseminating the findings of significant clinical research, major scientific breakthroughs, actionable discoveries, and state-of-the-art treatment pathways to the oncology community. Our ultimate objective is to facilitate the translation of new knowledge into tangible clinical benefits for individuals living with and surviving cancer.

期刊最新文献

Effects of the Oncology Industrial Complex on Academic Cancer Centers. Efficacy of Adding Veliparib to Temozolomide for Patients With MGMT-Methylated Glioblastoma: A Randomized Clinical Trial. Errors in Figure 3. Expanding Clinical Trial Accessibility in the Digital Era With Telemedicine. Expanding Clinical Trial Accessibility in the Digital Era With Telemedicine-Reply.