ADT is associated with physical side effects and a decline in cardiorespiratory fitness that can be mitigated with exercise (EX). Addition of a more potent androgen receptor inhibitor such as ENZ might worsen these effects. In this pilot study, we investigated whether an EX program could mitigate adverse changes from ADT + ENZ treatment.
Men starting ADT for M0 HSPC were treated with ADT + ENZ for 8 months and randomized to usual care (UC) or EX for 16 weeks. EX began 4 weeks prior to starting ADT + ENZ and consisted of 48 supervised exercise sessions delivered 3x/week between 55-80% of exercise capacity (VO2peak) for aerobic training and 60-85% of one repetition maximum (1-RM) for resistance training. The primary endpoint was change in VO2peak from baseline to 16 weeks. Secondary endpoints included 6 minute walk distance (6MWD), upper and lower body strength (1-RM), body composition (DXA), and patient reported outcomes (FACT-P, FACIT-Fatigue). The study was originally designed to recruit 56 subjects (N = 28/arm) but was halted early due to funding issues.
26 men (UC, N = 13; EX, N = 13) completed the protocol. Baseline age and BMI (mean ± standard deviation [SD]) were 65.0 ± 8.1 yr and 28.5 ± 4.6 kg/m2. Intention to treat analyses for mean 16-week change from baseline with a 95% confidence interval (CI) for each assessment by arm are presented in the table.Table: 1747P
|Endpoint||UC + ADT + ENZ (mean change [95% CI])||EX + ADT + ENZ (mean change [95% CI])|
|VO2peak (ml kg-1 min-1)||-3.2 (-6.3, -0.2)||-0.9 (-2.4, 0.5)|
|6MWD (ft)||-32.0 (-71.2, 7.3)||+42.0 (5.6, 78.4)|
|1-RM Leg Press (lbs)||+6.7 (-46.7, 60.0)||+107.1 (43.2, 171.0)|
|1-RM Chest Press (lbs)||+4.9 (-11.0, 20.9)||+24.3 (9.2, 39.4)|
|1-RM Row (lbs)||+3.0 (-10.5, 16.5)||+14.9 (0.7, 29.0)|
|Fat Mass (g)||+2949 (565, 5333)||-122 (-1593, 1350)|
|Lean Mass (g)||-3088 (-5384, -792)||-2094 (-3549, -640)|
|FACT-P TOI||-11.6 (-20.3, -2.9)||-5.4 (-10.8, 0.1)|
|FACIT-F Score||-9.2 (-16.0, -2.4)||-5.0 (-8.0, -2.1)|
Supervised aerobic and resistance EX resulted in less decline in VO2peak, as well as improved function and strength in men treated with ADT + ENZ for M0 HSPC. EX was associated with less fat gain and muscle mass loss, less decline in QOL, and less increase in fatigue. Larger trials of EX in this setting are warranted.
Clinical trial identification
Legal entity responsible for the study
Duke University Health System.
Pfizer (Medivation), Astellas.
All authors have declared no conflicts of interest.