A novel treatment approach may help to alleviate one of the most common and debilitating symptoms associated with cancer and its treatments—fatigue. According to data presented at the 2019 Supportive Care in Oncology Symposium,1 the combination of short-course dexamethasone plus standardized aerobic and resistance exercise demonstrated a synergistic effect in reducing cancer-related fatigue. Findings from the phase II, randomized, double-blind study showed sustained improvement in fatigue-related outcomes for up to 3 weeks after discontinuation of steroids. Patients in both arms also had improvement in myopathy, symptom distress, and sleep-quality scores. There was no worsening fasting blood glucose levels after dexamethasone use in both arms.
“In combination with exercise, the use of a short course of dexamethasone—both 4 mg twice daily and 8 mg twice daily—led to a significant improvement in cancer-related fatigue,” said lead author of the study, Sriram Yennu, MD, MS, FAAHPM, Professor of Palliative Care and Rehabilitation Medicine at The University of Texas MD Anderson Cancer Center, in Houston. “These data suggest that possible priming effects of steroids helped to sustain physical activity, but further larger studies are needed to confirm these findings.”
With low-dose dexamethasone and exercise, 50% of patients had reduced clinically relevant fatigue by day 29; with high-dose dexamethasone and exercise, 72% of patients experienced improvement.— Sriram Yennu, MD, MS, FAAHPM
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As Dr. Yennu explained, fatigue is not only common among patients with advanced cancer but has been shown to increase steadily in the last 6 months of life,2 with deleterious effects on patients’ physical, social, and emotional well-being. However, there are no pharmacologic treatments for fatigue approved by the U.S. Food and Drug Administration.
In addition, said Dr. Yennu, although dexamethasone has been studied in isolation to treat cancer-related fatigue, just 30% of patients have demonstrated a clinically relevant benefit, and there are potential long-term side effects. Physical activity, on the other hand, improves cancer-related fatigue, but there is lower adherence among patients with advanced cancer. Thus, Dr. Yennu and colleagues hypothesized that both dexamethasone and exercise may be used in a synergistic fashion to reduce the symptoms of fatigue.
For this phase II study, researchers enrolled patients with advanced cancer who had clinically significant fatigue (at least 4 of 10 on the Edmonton Symptom Assessment Scale [ESAS]) and excluded those with contraindications to either dexamethasone or exercise. Researchers randomly assigned patients to either 4 mg of dexamethasone (low-dose dexamethasone) or 8 mg of dexamethasone (high-dose dexamethasone) orally, twice daily for 7 days, plus standardized aerobic and resistance exercise for 4 weeks.
The study’s primary outcome was change in the Functional Assessment of Chronic Illness–Fatigue (FACIT-Fatigue) subscale from baseline to day 8 and day 29. Secondary outcomes included changes in fatigue (ESAS, Patient-Reported Outcome Measurement Information System [PROMIS], Multidimensional Fatigue Symptom Inventory [MFSI]), sleep quality, fasting blood glucose, and myopathy.
Improvement in Symptoms of Fatigue
The median age of the cohort was 59 years, and the most common cancers were breast, gastrointestinal, and genitourinary. Of the 67 patients enrolled in the study, 60 were evaluable, said Dr. Yennu, who noted that the treatment was well tolerated, despite high levels of baseline fatigue (21 of 52 on the FACIT-Fatigue scale).
Data showed that 84% and 65% of patients on low-dose dexamethasone were adherent to aerobic and resistance exercise, respectively. Adherence to aerobic and resistance exercise was even higher for patients receiving high-dose dexamethasone at 96% and 68%, respectively. All patients were adherent to the study medication. No significant difference in grade 3 or higher adverse events were observed between the two arms (P = .92), Dr. Yennu reported.
Regarding the primary outcome, the researchers observed significant improvements in cancer-related fatigue, with an effect size of 0.49 and 0.45 with low-dose and high-dose dexamethasone, respectively. Dr. Yennu called this outcome a “very robust improvement in fatigue level,” with improvements in FACIT-Fatigue scores of at least 14 points on both arms. What’s more, added Dr. Yennu, these changes were consistent with other measurement tools. Similar improvement was found with the ESAS for Fatigue (P < .001), MFSI total (P = .005), and PROMIS-fatigue total (P = .005).
The Edmonton Symptom Assessment is designed to assist in the assessment of 9 symptoms—pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath—on a scale of 0 to 10, and can be completed in less than 1 minute.
“Of note, these data demonstrate a clinically relevant benefit to adding exercise to dexamethasone,” said Dr. Yennu. “With low-dose dexamethasone and exercise, 50% of patients had reduced fatigue, which was clinically relevant by day 29; with high-dose dexamethasone and exercise, 72% of patients experienced improvement.”
Finally, sleep-quality and myopathy scores were improved, and there was no worsening fasting blood glucose levels after dexamethasone use in both arms during and after the intervention. Despite the observed benefits, however, Dr. Yennu acknowledged that this study was only designed to assess feasibility. Further larger studies are required to confirm this synergistic effect on fatigue, he concluded.■
DISCLOSURE: Dr. Yennu has received research funding from Bayer, Genentech/Roche, and Helsinn Therapeutics.
1. Yennu S, Valero V, Lim B, et al: High/low dose dexamethasone with physical activity for cancer-related fatigue in patients with advanced cancer: A phase II randomized double blind study. 2019 Supportive Care in Oncology Symposium. Abstract 110. Presented October 26, 2019.
2. Seow H, Barbera L, Sutradhar R, et al: Trajectory of performance status and symptom scores for patients with cancer during the last six months of life. J Clin Oncol 29:1151-1158, 2011.
Eduardo Bruera, MD, FAAHPM
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