A randomized controlled trial comparing changes in fitness with or without supervised exercise in patients initiated on enzalutamide and androgen deprivation therapy for non-metastatic castration-sensitive prostate cancer (EXTEND) Journal Article
| Authors: | Harrison, M. R.; Davis, P. G.; Khouri, M. G.; Bartlett, D. B.; Gupta, R. T.; Armstrong, A. J.; McNamara, M. A.; Zhang, T.; Anand, M.; Onyenwoke, K.; Edwardson, S.; Craig, D.; Michalski, M.; Wu, Y.; Oyekunle, T.; Coyne, B.; Coburn, A.; Jones, L. W.; George, D. J. |
| Article Title: | A randomized controlled trial comparing changes in fitness with or without supervised exercise in patients initiated on enzalutamide and androgen deprivation therapy for non-metastatic castration-sensitive prostate cancer (EXTEND) |
| Abstract: | Background: Androgen deprivation therapy (ADT) and androgen receptor signaling inhibitors (ARSI) are associated with deleterious physical effects, which exercise may mitigate; however, exercise has never been studied in patients initiating treatment with ADT and an ARSI. Our objective was to determine whether supervised exercise prior to and during initial therapy could mitigate adverse effects of ADT plus enzalutamide. Methods: We conducted a single center trial in patients with recurrent prostate cancer treated with ADT and enzalutamide. We randomized 26 patients to 16 weeks of supervised exercise (aerobic and resistance), starting 4 weeks before initiation of ADT and enzalutamide, or usual care. The primary endpoint was change in peak oxygen uptake (VO2peak) as a measure of cardiorespiratory fitness (CRF). Secondary endpoints were functional capacity, maximal strength, body composition, patient-reported outcomes, safety, and feasibility. Analysis of covariance was used to compare outcomes for groups at Week 17 adjusted for baseline values. Results: The usual care group (N = 13) showed declines from baseline to week 17 in both absolute CRF (−0.31 L/min, −10.9%; p < 0.01) and relative CRF (−3.2 mL/kg/min, −8.9%; p = 0.04); worse fatigue (p = 0.01); and worse quality of life (p = 0.01). At week 17, the exercise group (N = 13) demonstrated improved absolute CRF (between-group change +0.20 L/min, p = 0.05), leg strength (+48.6 kg, p < 0.01) and functional capacity (+21.0 m, p = 0.01) at week 17. Conclusions: This is the first randomized controlled trial demonstrating a clinically significant decline in CRF in patients initiating ADT and enzalutamide. We show the effectiveness of short-term supervised exercise to mitigate declines in absolute CRF, and improve maximal leg strength and functional capacity. ClinicalTrials.gov Identifier: NCT02256111 © 2022, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | clinical article; controlled study; aged; androgen; fatigue; cancer recurrence; cancer patient; cancer radiotherapy; prospective study; prostate specific antigen; quality of life; neoplasm recurrence, local; randomized controlled trial; exercise; gleason score; prostatic neoplasms; feasibility study; prostatectomy; tumor recurrence; prostate tumor; androgen antagonists; safety; body composition; antiandrogen; orchiectomy; androgen deprivation therapy; functional status; strength; androgens; nitriles; aerobic exercise; nitrile; kinesiotherapy; phenylthiohydantoin; benzamide derivative; benzamides; complication; clinical outcome; exercise therapy; patient-reported outcome; enzalutamide; cardiorespiratory fitness; humans; human; male; article; resistance training; leg muscle; castration sensitive prostate cancer; peak oxygen uptake; supervised exercise |
| Journal Title: | Prostate Cancer and Prostatic Diseases |
| Volume: | 25 |
| Issue: | 1 |
| ISSN: | 1365-7852 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2022-03-01 |
| Start Page: | 58 |
| End Page: | 64 |
| Language: | English |
| DOI: | 10.1038/s41391-022-00519-4 |
| PUBMED: | 35273377 |
| PROVIDER: | scopus |
| PMCID: | PMC9983359 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2022 -- Source: Scopus |
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