DEXAMETHASONE REDUCES CANCER FATIGUE

Dexamethasone can reduce cancer-related fatigue in patients with advanced disease and can improve quality of life, but few oncologists use the steroid to manage fatigue at the end of life.

In a small randomized clinical trial, published online July 29 in the Journal of Clinical Oncology, dexamethasone significantly improved quality of life, physical well-being, and physical distress, compared with placebo.

Although larger long-term efficacy and safety studies are needed, dexamethasone can be an option for patients who are experiencing a great deal of distress because of fatigue and related symptoms, said lead author Sriram Yennurajalingam, MD, from the Department of Palliative Care and Rehabilitation Medicine at the University of Texas M.D. Anderson Cancer Center in Houston.

"It can be prescribed for about 1 to 2 weeks in all advanced cancer patients with significant cancer-related fatigue," he toldMedscape Medical News.

However, it is not used much in this setting. In a recent surveyof 1000 oncologists conducted by the National Comprehensive Cancer Network, just one quarter to one third of respondents said that they frequently use steroids to manage fatigue at the end of life.

"Dexamethasone is used on a limited basis in this setting because of concerns about side effects and lack of evidence in the form of clinical trials with fatigue as a primary outcome," Dr. Yennurajalingam explained.

Improvement Seen in Multiple Measures

In their study, Dr. Yennurajalingam and colleagues evaluated 84 patients with a diagnosis of advanced cancer who had experienced 3 or more symptoms during the previous 24 hours (i.e., pain, fatigue, chronic nausea and anorexia/cachexia, sleep problems, depression, or poor appetite). They were randomized to receive oral dexamethasone 4 mg or placebo twice daily for 14 days.

The primary end point was change from baseline to day 15 on the fatigue subscale of the Functional Assessment of Chronic Illness Therapy (FACIT-F). Secondary outcomes included anorexia, anxiety, depression, and symptom distress scores.

Mean improvement in FACIT-F score was significantly better with dexamethasone than with placebo. The mean improvement from baseline in FACIT-F score was significantly better at day 8 (P = .012) and day 15 (P = .001), even after adjustment for sex.

In addition, the mean improvement in FACIT total quality-of-life score was significantly better in the dexamethasone group than in the placebo group at day 15 (P = .03). FACIT physically well-being scores were significantly better at day 8 (P = .007) and day 15 (P = .002) in the dexamethasone group.

Physical distress scores on the Edmonton Symptom Assessment Scale (ESAS) were significantly better at days 8 and 15. However, other improvements were not statistically significant, including changes in ESAS individual symptoms, psychological distress, and Hospital Anxiety and Depression Scale anxiety and depression scores.

Pain assessed with the ESAS was significantly better in the dexamethasone group at day 8, as were Functional Assessment of Anorexia/Cachexia Therapy (FAACT) scores at day 15 (P = .013).

Mixed Interventions

A patient with severe cancer-related fatigue who found that dexamethasone gave her a "satisfactory response for both pain and fatigue" is discussed in an accompanying case study.

Pleun J. de Raaf, MD, and Carin C.D. van der Rijt, MD, PhD, both from the Erasmus MC–Daniel den Hoed Cancer Center in Rotterdam, the Netherlands, note that a number of nonpharmacologic and pharmacologic interventions have been proposed to treat fatigue in patients with advanced disease.

"Because fatigue in advanced cancer is not an isolated symptom, evaluation should begin with screening for concurrent symptoms in patients with moderate–severe fatigue," they write. "Furthermore, because fatigue may be secondary to a variety of complications resulting from the cancer, cancer treatment, or comorbid conditions, a targeted history, physical examination, and additional diagnostics must be considered depending on potential risks and benefits for the patient."

The 64-year-old woman they describe had metastatic rectal cancer and was admitted to an acute palliative care unit because of debilitating fatigue. She was bedridden because of progressive fatigue and complained of dyspnea, nausea and vomiting, and pain in the upper abdomen.

Drs. de Raaf and van der Rijt note that a specialized nurse provided this patient with psychoeducation and she was treated with analgesic and antiemetic medications and twice-daily oral dexamethasone 4 mg. She achieved a satisfactory response for both pain and fatigue.

"In patients with fatigue that proves refractory to psychoeducation and simple symptom control, clinicians can recommend corticosteroids or methylphenidate," they write. "We propose the use of corticosteroids in situations with concurrent anorexia, nausea, or vomiting, or in those with corticosteroid responsive complications such as intracranial hypertension, hepatic distension, and lymphangitic carcinomatosis."

The long-term beneficial effects of corticosteroids have not been shown, but they can cause serious adverse effects after several weeks. Therefore, steroids are recommended only for patients with a limited life expectancy or those with reversible underlying reasons for the fatigue.

The study was supported by a Mentored Research Scholar Grant from the American Cancer Society. Coauthor Janet Bull, PhD, from Four Seasons Hospice in Flat Rock, North Carolina, reports receiving honoraria from Salix Pharmaceutical and Meda Pharmaceutical. None of the other authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online July 29, 2013. Abstract, Case study