Physical Activity and Dexamethasone for Cancer-Related Fatigue: A Preliminary Placebo-Controlled, Randomized, Double-Blind Trial

Background: Physical activity (PA) and dexamethasone (Dex) when used independently have modest benefits for cancer-related fatigue (CRF) in patients with advanced cancer. In this study we aimed to determine the feasibility (adherence, safety, and satisfaction) of combining PA with Dex versus PA with placebo (PBO) for CRF, and to explore the effects of PA+Dex and PA+PBO on CRF. Patients and Methods: In this phase II, randomized, double-blind controlled trial, eligible patients had advanced cancer and a CRF score of ≥4 on the Edmonton Symptom Assessment Scale (ESAS) for fatigue (0–10 scale). Patients were randomized to standardized PA for 4 weeks with either 4 mg of Dex (PA+Dex arm) or PBO (PA+PBO arm) twice daily for the first 7 days. Changes in Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) scores from baseline to days 8 and 29 were assessed. Other outcomes included change in quality-of-life scores. Results: A total of 64 (89%) patients were evaluable. Adherence rates for study medication, resistance exercise, and aerobic exercise were 91% and 92% ( P =.15), 83% and 70.6% ( P =.35), and 82.9% and 78.3% ( P =.73), respectively, in the PA+Dex and PA+PBO arms. The satisfaction rates for the PA+Dex and PA+PBO arms were 98% and 79%, respectively. Median (IQR) changes in FACIT-F scores at days 8 and 29 from baseline were 9 (2 to 16; P <.001) and 5.75 (0 to 12.5; P =.015) for the PA+Dex arm, respectively, and 3.5 (−2.1 to 10; P =.054) and 6.5 (2.5 to 15.5; P =.006) for the PA+PBO arm, respectively. We found a significant treatment effect in the PA+Dex arm using exploratory linear mixed model analysis, with treatment showing an improvement of 5.63 units for FACIT-F scores (95% CI, 1.74–9.52; P =.005). We found significant improvement in Functional Assessment of Cancer Therapy-General (FACT-G), Patient-Reported Outcomes Measurement Information System-Fatigue Short Form 7a (PROMIS-Fatigue SF-7a), and Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) totals on days 8 and 29 in the PA+Dex arm. There was no significant difference in grade ≥3 adverse events between the arms ( P =.36). Conclusions: Our study found that the use of combination PA+Dex and PA+PBO for CRF was feasible and associated with high rates of satisfaction, adherence to medication and PA intervention, and tolerability. CRF improvement with PA+Dex was clinically significant at days 8 and 29. Further larger studies are justified. ClinicalTrials.gov identifier: NCT03583255