Hui, D., Kilgore, K., Frisbee-Hume, S., Park, M., Tsao, A., Delgado Guay, M., . . . Bruera, E. (2016). Dexamethasone for dyspnea in cancer patients: A pilot double-blind, randomized, controlled trial. Journal of Pain and Symptom Management, 52, 8-16.e1

To determine the feasibility of conducting a randomized trial of dexamethasone in patients with cancer and the estimated efficacy of dexamethasone in the treatment of dyspnea.

Patients were randomly assigned to a 1:1 ratio to receive either dexamethasone 8 mg (two capsules of 4 mg) orally twice a day for four days, then 4 mg given orally twice a days for three days or identical-appearing placebo capsules. After one week, patients received dexamethasone 4 mg orally twice a day for seven days in open-label fashion.

• N = 41 patients; 77 eligible for study, 52 enrolled, 11 became ineligible or declined to continue  
• AGE: Mean age = 63 years (range = 48-78)
• MALES: 39%  
• FEMALES: 61%
• CURRENT TREATMENT: Radiation 
• KEY DISEASE CHARACTERISTICS: A majority of patients (88%) had advanced cancer, with lung cancer being the most common diagnosis (81%). If not primary lung cancer, all had clinical or radiologic evidence of lung involvement.
• OTHER KEY SAMPLE CHARACTERISTICS: Other requirements: average dyspnea of 4 or greater over past week, Karnofsky PS of 40% or greater, undergoing radiation therapy, but not chemotherapy within one week. Exclusions: uncontrolled diabetes, severe anemia, oxygen at less than 90% on greater than 6 L per minute oxygen, megestrol use, delirium, open unhealed wound, recent corticosteroid use for greater than 14 days

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: University of Texas MD Anderson Cancer Center

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care

Double-blind, parallel, placebo-controlled, randomized trial

Dyspnea was assessed at baseline, day 4+ or -2, day 7+ or -2, and day 14+ or -2. The Edmonton Symptom Assessment System (ESAS) was used. Dyspnea “now” was assessed using the Modified Dyspnea Borg Scale. The Cancer Dyspnea Scale as well as the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-C30) was used. MicroLoop Spirometer was used at baseline to obtain FEV1, FVC, FEV1/FEV2, peak inspiratory flow, and peak expiratory flow. Patients used the portable Microlife PF 100 Peak Flow Meter daily to measure peak flow and FEV1. A priori was considered that the study was feasible if at least 50% of patient completed the study. Twenty patients per arm provided 80% power to detect an effect size as small as 0.66 within arms with a two-tailed alpha of 0.05. To estimate effect size, the within-arm mean differences between baseline and day 4, 7, and 14 along with the 95% CI for dyspnea was determine and applied the Wilcoxon signed-rank test. The Statistical Analysis System was used for statistical analysis.

Dexamethasone was associated with a significant reduction in ESAS dyspnea NRS of -1.9 (p = 0.01) by day 4 and -1.8 (p = 0.02) by day 7. Placebo was associated with a reduction of -0.7 (p = 0.38) by day 4 and -1.3 (p =  0.03) by day 7. After one week of open-label treatment, both arms had improvement in dyspnea by day 14 (p = 0.01 for dexamethasone, placebo p = 0.004). The dyspnea numeric scale showed similar results by day 14. EORTC showed improvements in dyspnea in the dexamethasone arm by day 4 (p = 0.04). ESAS drowsiness improved in the dexamethasone arm by day 4 (p = 0.03) and day 7 (p = 0.01), but not by day 14; however, baseline drowsiness was higher in the dexamethasone arm. Dexamethasone was well-tolerated with no grade 3 toxicities.

Dexamethasone showed to improve dyspnea with minimal adverse effects. Feasibility of a randomized controlled trial without unacceptable attrition was validated. More testing needs to be completed to determine absolute efficacy.

• Small sample (< 100)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Subject withdrawals ≥ 10%
• Other limitations/explanation: 85% of patients completed week 1 of the study and 71% of patients completed week 2. This study focused on patients who had lung involvement with cancer. The sample size was small and hence the study was not powered to detect differences.  Co-interventions were not defined. The study was not powered to compare dexamethasone to the placebo, so no definitive conclusion can be made regarding the efficacy of dexamethasone compared to the placebo. The study description said patients were stratified into FEV1/FVC groups, but group differences were not reported.

Nurses may consider using corticosteroids management of dyspnea for patients with severe dyspnea when no obvious reversible etiologies and targeted interventions exist. Nurses need to be aware of the potential adverse reactions associated with corticosteroids and educate patients on such. Nurses need to be aware of the various routes of administration for corticosteroids.