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2022 Stupski Foundation-PCF Challenge Award

Debunking the Frailty-SarcopenIa-ADT Axis in MEtastatic Prostate CanceR with MultiCompenent Exercise: The FIERCE Trial

Principal Investigator: Christina Dieli-Conwright, PhD, MPH (Dana-Farber Cancer Institute)

Co-Investigators: Rebekah Wilson, PhD (Dana-Farber Cancer Institute), Alicia Morgans, MD (Dana-Farber Cancer Institute), Michael Rosenthal, MD, PhD (Dana-Farber Cancer Institute), Hajime Uno, PhD (Dana-Farber Cancer Institute), Matthew Vander Heiden, MD, PhD (Dana-Farber Cancer Institute)

Description:

  • Androgen deprivation therapy (ADT), the mainstay treatment for advanced prostate cancer, can cause a number of side effects, including decline in muscle mass and physical function, which exacerbates age-related conditions such as frailty and sarcopenia (a decrease in muscle mass, strength, and function). Frailty and sarcopenia are associated with worse outcomes and shorter survival in patients with prostate cancer.
  • Patients who received ADT are 3 times more likely to develop frailty compared to patients who never received ADT and 2 times more likely to develop sarcopenia compared to men without cancer.
  • Exercise plays a key role in resolving or preventing these ADT-related side effects and improving muscle mass, fitness, and strength.
  • Multicomponent exercise incorporates resistance and aerobic training combined with functional movements (e.g., balance) and can maximize the beneficial effects of exercise on physical function, muscular strength/endurance, and body composition, and is recommended for improving/preventing frailty and sarcopenia.
  • The impacts of exercise have been vastly understudied in men with metastatic prostate cancer. Studies on frailty and sarcopenia and the mechanisms of how exercise could address such outcomes, are especially needed.
  • Dieli-Conwright is an expert in exercise oncology and has led multiple clinical trials evaluating the impact of exercise in patients with prostate and other cancers.
  • In this project, Dr. Dieli-Conwright and team will conduct a clinical trial, “FIERCE,” to assess the effects of a 16-week multicomponent exercise intervention, encompassing resistance, aerobic, and functional training, on frailty, sarcopenia, and disease progression, in men with metastatic prostate cancer receiving ADT.
  • Eighty men with metastatic prostate cancer receiving ADT will be randomized to the exercise or attention control group. The 16-week exercise intervention will include 3x per week clinic-supervised resistance and functional exercise circuit training, and self-directed home-based aerobic exercise. The attention control group will receive a stretching program and will be offered the exercise program following the study period. The impacts on frailty and sarcopenia will be measured and compared.
  • In addition, samples from patients will be used to identify biomarkers of exercise effects and potential mechanisms of how exercise may improve frailty and sarcopenia. For instance, inflammatory and muscle activity markers will be evaluated. These mechanisms will be further studied and validated in preclinical prostate cancer models.

What this means to patients:  ADT is the standard backbone treatment for patients with aggressive and advanced prostate cancer, but can cause significant side effects, including exacerbation of frailty and sarcopenia.  Dr. Dieli-Conwright and team will conduct a clinical trial to test the impact of a multicomponent exercise intervention on frailty and sarcopenia in men undergoing treatment with ADT.  The team will also identify biomarkers of response and mechanisms by which exercise improves these functions.  If successful, this study will establish an exercise treatment program to prevent degenerative effects of ADT and significantly improve quality of life and outcomes in men with prostate cancer.