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

Autor:	Jones LW; Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., Moskowitz CS; Memorial Sloan Kettering Cancer Center, New York, New York., Lee CP; Memorial Sloan Kettering Cancer Center, New York, New York., Fickera GA; Memorial Sloan Kettering Cancer Center, New York, New York., Chun SS; Memorial Sloan Kettering Cancer Center, New York, New York., Michalski MG; Memorial Sloan Kettering Cancer Center, New York, New York., Stoeckel K; Memorial Sloan Kettering Cancer Center, New York, New York., Underwood WP; Memorial Sloan Kettering Cancer Center, New York, New York., Lavery JA; Memorial Sloan Kettering Cancer Center, New York, New York., Bhanot U; Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., Linkov I; Memorial Sloan Kettering Cancer Center, New York, New York., Dang CT; Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., Ehdaie B; Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., Laudone VP; Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., Eastham JA; Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell Medical College, New York, New York., Collins A; Memorial Sloan Kettering Cancer Center, New York, New York., Sheerin PT; Memorial Sloan Kettering Cancer Center, New York, New York., Liu LY; Institute for Precision Health, University of California, Los Angeles.; Jonsson Comprehensive Cancer Center, University of California, Los Angeles.; Department of Urology, University of California, Los Angeles., Eng SE; Institute for Precision Health, University of California, Los Angeles.; Jonsson Comprehensive Cancer Center, University of California, Los Angeles.; Department of Urology, University of California, Los Angeles., Boutros PC; Institute for Precision Health, University of California, Los Angeles.; Jonsson Comprehensive Cancer Center, University of California, Los Angeles.; Department of Urology, University of California, Los Angeles.; Department of Human Genetics, University of California, Los Angeles.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	JAMA oncology [JAMA Oncol] 2024 Sep 01; Vol. 10 (9), pp. 1187-1194.
DOI:	10.1001/jamaoncol.2024.2156
Abstrakt:	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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu