Exercise prescription dose for castrate-resistant prostate cancer patients: a phase I prescription dose escalation trial

Abstract

Purpose: To determine the start exercise prescription dose in metastatic castrate-resistant prostate cancer (mCRPC) patients receiving second-line hormone treatment and recommended phase II exercise prescription.

Methods: Patients were enrolled in a 3 + 3 dose escalation phase I trial of aerobic, resistance, and flexibility exercises to evaluate dose-limiting tolerance and safety. Tolerance was defined as Borg score ≤ 16 and safety (pain) as a visual analogue scale score (VAS) ≤ 3 and CTCAE grade < 2. Dose level 1 (escalation start dose) was set at 15 min. Aerobic training (50-80% HRmax warm-up and cooling-down; and 65-80% HRmax. core), 1 set with 8-10 repetitions (reps.) resistance training (50-60% 1-RM, 8 exercises), and 1 set (30s) with 2 reps flexibility training (5 exercises). The prescription dose escalation was designed in four levels (from dose -1 to 3), with a dose escalation in volume and intensity of the exercises.

Results: Nine patients were included in two dosing cohorts and were under active treatment (n = 4 abiraterone acetate and n = 5 enzalutamide). Dose limiting safety concerns were observed in 2 out of 3 patients in dose level 2 and 1 patient out of 6 in dose level 1 due to VAS > 3 during resistance training and/or flexibility training. No tolerance issues were observed in the two dosing cohorts. The optimal start exercise prescription dose was set at dose level 1 due to safety issues at dose level 2.

Conclusion: Our findings suggest that exercise is perceived tolerable in mCRPC patients receiving second-line hormone therapy. Caution is indicated on safety during performance of the exercises.

Keywords: Castration-resistant prostate cancer; Exercise; Phase 1; Physical activity.