High/low dose dexamethasone with physical activity for cancer-related fatigue in patients with advanced cancer: A phase II randomized double blind study.

Abstract

110 Background: Cancer-related-fatigue (CRF) is the most debilitating symptom in patients with advanced cancer. Physical activity (PA) improves CRF with lower adherence in advanced cancer. Dexamethasone (Dex) improves CRF but has long-term side effects. The purpose of the study was to determine whether a brief course of Dex improves adherence to PA for CRF management. Methods: Advanced cancer patients with CRF ≥ 4/10 on Edmonton Symptom Assessment Scale (ESAS) were eligible. Patients were randomized to either 4mg of Dex (LoDex) or 8mg of Dex (HiDex) orally BID for 7 days Plus standardized aerobic and resistance exercise for 4 weeks. Change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) fatigue subscale from baseline to Day 8 (primary outcome) and Day 29 were assessed. Secondary outcomes included changes in fatigue (ESAS, PROMIS, MFSI), Sleep Quality (PSQI), fasting blood glucose, and myopathy. Results: Total evaluable patients were 60 (31 LoDex and 29 HiDex arms). The study was feasible (N = 60/67 were evaluable); 84% and 65% LoDex, and 96% and 68% Hi Dex were adherent to aerobic and resistance exercise, respectively [All Patients were adherent to study medication]. There was no significant difference in grade 3+ AE’s between the two arms (P = 0. 92). The FACIT fatigue subscale Cohen’s d in Lo Dex was 0.90 (P < 0.001) and 0.94(P < 0.001); and Hi Dex was 0.86(P < 0.001); and 1.05(P < 0.001) at Day 8 and Day 29, respectively. Similar improvement was found for ESAS Fatigue (P < 0.001), MFSI total (P = 0.005), and PROMIS –fatigue total (P = 0.005). Mixed model analysis showed significant improvement in FACIT-F fatigue scores at Day 8 (P = 0.0006), Day 15 (P = 0.0002), and D (P = 0.0018). There was no significant difference between the two arms at Day 8 and Day 29 in fatigue scores, myopathy, fasting blood glucose levels, symptom distress, and sleep quality scores. Conclusions: Short course of dexamethasone Plus physical activity resulted in sustained and robust improvement in CRF outcomes for upto 3 weeks after discontinuation of steroids suggesting possible priming effects of steroids helped to sustain physical activity. Further larger studies are justified. Clinical trial information: NCT02491632.