Steroids plus Exercise Reduce Fatigue in Patients with Advanced Cancer

Steroids plus exercise could be the best combination for treating fatigue in patients with advanced cancer, according to data presented at the 2019 Supportive Care in Oncology Symposium.

In a phase 2 clinical trial, short-course dexamethasone plus standardized aerobic and resistance exercise resulted in sustained and robust reductions in cancer-related fatigue for up to 3 weeks after discontinuation of steroids. Patients also had improvements in myopathy, fasting blood glucose levels, symptom distress, and sleep quality scores.

“The use of short-course dexamethasone, both 4 mg twice daily and 8 mg twice daily, led to a significant improvement in cancer-related fatigue when combined with exercise,” said lead investigator Sriram Yennu, MD, MS, FAAHPM, Professor, Department of Palliative, Rehabilitation and Integrative Medicine, M.D. Anderson Cancer Center, Houston, TX. “These data suggest that possible priming effects of steroids helped to sustain physical activity, but further larger studies are needed to confirm these findings.”

Fatigue is one of the most common symptoms in patients with advanced cancer and has been found to intensify progressively in the last 6 months of life, Dr Yennu said. Moreover, fatigue is associated with adverse effects on patients’ physical, social, and emotional well-being.

Nevertheless, there is no FDA-approved medication for fatigue. Although dexamethasone has been studied as a monotherapy for cancer-related fatigue, said Dr Yennu, less than 33% of patients had benefit, and there are potential long-term side effects. In contrast, exercise has been shown to reduce symptoms of fatigue, but adherence to exercise is relatively low among patients with advanced cancer.

Study Details

This phase 2, randomized, double-blind study enrolled advanced patients with fatigue scores of at least 4:10 on the Edmonton Symptom Assessment Scale (ESAS). Those with contraindications to dexamethasone or exercise were excluded.

Patients were randomized to 4 mg of dexamethasone or to 8 mg of dexamethasone, taken twice daily for 7 days, plus standardized aerobic and resistance exercise for 4 weeks.

The study’s primary outcome was change in fatigue from baseline to Day 8 and Day 29, as assessed by the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) fatigue subscale. Secondary outcomes included changes in fatigue, sleep quality, fasting blood glucose, and myopathy.

A total of 60 patients were evaluable, showing significant reductions in cancer-related fatigue, with a score of 0.49 with 4-mg dexamethasone and 0.45 with 8-mg dexamethasone.

“These outcomes indicate sustained and very robust improvement in fatigue scores,” said Dr Yennu, who noted that FACIT-F scores increased by at least 14 points in both arms. These changes were consistent with other measurement tools, including ESAS Fatigue (P <.001), MFSI total (P = .005), and PROMIS–fatigue total (P = .005).

“Most important, these data demonstrate a clinically relevant benefit to adding exercise to dexamethasone,” said Dr Yennu. “With low dexamethasone and exercise, 50% of patients had reduced fatigue by Day 29, and in the high dexamethasone group, 72% of patients experienced improvement.”

Adherence to treatment was also significantly improved compared with historical data. A total of 84% and 65% of patients receiving 4-mg dexamethasone were adherent to aerobic and to resistance exercise, respectively. Adherence was even higher at 96% and 68%, respectively, for patients receiving 8-mg dexamethasone, and all patients were adherent to the study medication, Dr Yennu reported.

Finally, the combination of dexamethasone and physical activity also led to improvements in sleep quality scores, myopathy, and fasting blood glucose levels. Despite these positive findings, the investigators acknowledged that this study was only designed to assess feasibility. Larger studies are needed to confirm this synergistic effect on fatigue, Dr Yennu concluded.

“There are challenges with the use of corticosteroids in the area of supportive and palliative care, but there are potentially great advantages that we need to continue to explore,” said Eduardo Bruera, MD, FAAHPM, Department Chair, Department of Palliative, Rehabilitation and Integrative Medicine, M.D. Anderson Cancer Center.

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