Benefits Balanced with Harm

Corticosteroids, Systemic

for Fatigue

Corticosteroids are a class of steroid hormones produced in the adrenal cortex. They are involved in a wide range of physiologic systems such as the stress and immune responses, the regulation of inflammation, carbohydrate metabolism, and protein catabolism. Corticosteroids can be administered orally, intravenously, or topically and are used to treat a variety of conditions. Drugs in this class include dexamethasone, methylprednisone, prednisone, hydrocortisone, mometasone, betamethasone, and fludrocortisones. Systemic corticosteroids have been examined in for their efficacy in the management of anorexia and pain, and specific, individual corticosteroids typically are part of drug regimens to treat chemotherapy-induced nausea and vomiting. The systemic administration of corticosteroids has been examined for effects on arthralgia associated with cancer treatment using aromatase inhibitors because of the anti-inflammatory property of steroids.

Systematic Review/Meta-Analysis

Begley, S., Rose, K., & O'Connor, M. (2016). The use of corticosteroids in reducing cancer-related fatigue: Assessing the evidence for clinical practice. International Journal of Palliative Nursing, 22, 5–9.

Purpose

STUDY PURPOSE: To assess the evidence regarding the use of corticosteroids for fatigue among patients with advanced cancer

TYPE OF STUDY: Systematic review

Search Strategy

DATABASES USED: PubMed, CINAHL, Cochrane Collaboration
 
KEYWORDS: Advanced cancer, terminal, palliative care, end-stage disease, fatigue, lethargy, weakness, cancer-related fatigue, corticosteroids, dexamethasone, prednisolone, methylprednisolone
 
INCLUSION CRITERIA: Not stated
 
EXCLUSION CRITERIA: Not stated

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 12
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Not described

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 4
  • TOTAL PATIENTS INCLUDED IN REVIEW = Not provided
  • SAMPLE RANGE ACROSS STUDIES: Not provided
  • KEY SAMPLE CHARACTERISTICS: All studies were of patients with advanced disease with minimal life expectancy.

SAMPLE RANGE ACROSS STUDIES, 

Phase of Care and Clinical Applications

  • PHASE OF CARE: End-of-life care
  • APPLICATIONS: Palliative care

Results

All studies reported improvement in patient-reported fatigue. Gaps were noted in information regarding side effects and the specifics of the dosage, etc., of the intervention.

Conclusions

Corticosteroids may improve fatigue in patients with advanced cancer, but potential adverse side effects have not been examined well.

Limitations

  • Limited number of studies
  • No details of included studies, such as sample sizes, etc., were provided.

Nursing Implications

Corticosteroids may improve fatigue in patients with cancer, but insufficient information about adverse effects exists. Steriods should not be used for a long duration—an intervention that may be useful for patients who desire short-term improvement in feelings of fatigue to participate in family events, etc.

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Research Evidence Summaries

Paulsen, O., Klepstad, P., Rosland, J.H., Aass, N., Albert, E., Fayers, P., & Kaasa, S. (2014). Efficacy of methylprednisolone on pain, fatigue, and appetite loss in patients with advanced cancer using opioids: A randomized, placebo-controlled, double-blind trial. Journal of Clinical Oncology. Advance online publication. 

Study Purpose

To compare the analgesic efficacy of corticosteroid therapy versus a placebo

Intervention Characteristics/Basic Study Process

The intervention was methylprednisolone 32 mg daily for seven days. The research team used a computerized randomization program to assign participants to intervention or placebo groups. Randomization stratification was based on study center and verified pain related to bone metastases. Both the research team and study participants were blinded to study assignment. Pain intensity, fatigue, and appetite loss were measured at baseline and day 7. Analgesic use was recorded daily. Satisfaction with the intervention was measured at day 7. Semistructured interviews were conducted at day 7 to determine any adverse effects experienced by study participants.

Sample Characteristics

  • N = 49  
  • MEAN AGE: 64 years
  • MALES: 51%, FEMALES: 49% 
  • KEY DISEASE CHARACTERISTICS: Cancer diagnoses were breast, prostate, gastrointestinal, lung, gynecologic, and “other.” All patients but one in each arm of the study had metastatic disease. Seven participants were receiving chemotherapy and six were receiving hormonal therapy; pain score > 4.
  • OTHER KEY SAMPLE CHARACTERISTICS: Mean Karnofsky score was 62.5 (intervention group) and 66.0 (placebo group)

Setting

  • SITE: Multi-site    
  • SETTING TYPE: Multiple settings    
  • LOCATION: Norway

Phase of Care and Clinical Applications

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

Study Design

Placebo-controlled, double-blind, randomized controlled trial

Measurement Instruments/Methods

  • Brief Pain Inventory (BPI)
  • Edmonton Symptom Assessment System (ESAS)
  • European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ–C30)
  • Satisfaction measured with intervention Numeric Rating Scale (NRS)
  • Patient diary for recording daily analgesics
  • Semistructured interviews

Results

No significant difference was found between groups for average pain intensity at day 7, change in pain intensity from baseline, opioid intake, or adverse events. However, the intervention group did have a significant improvement in fatigue (p = .003) and appetite (p = .003) at day 7 compared to the placebo group. In addition, their overall satisfaction with treatment was also significantly greater (p = .001).

Conclusions

Pain relief was not improved for patients with advanced cancer who were taking on average a 222 mg oral morphine equivalent dose (MED). It is unknown whether this may be effective for different patient populations such as those taking a lower MED. Improvement in fatigue and appetite and a low number of adverse events were important clinical outcomes. Further study is needed to determine the long-term effects of this intervention.

Limitations

  • Small sample (< 100)
  • Baseline sample/group differences of import
  • Other limitations/explanation: Intervention group had a significantly higher dosage of MEDs compared to the control group

 

Nursing Implications

Nurses should be aware that methylprednisolone 32 mg daily may not be effective for improving pain relief in patients with advanced cancer who are taking an average opioid dose of ≥ 220 MED; however, it may improve fatigue and appetite with minimal adverse effects. Long-term effects have not yet been established. Long-term steroid use can contribute to other adverse side effects and should be weighed carefully with benefit of treatment.

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Yennurajalingam, S., Frisbee-Hume, S., Palmer, J.L., Delgado-Guay, M.O., Bull, J., Phan, A.T., . . . Bruera, E. (2013). Reduction of cancer-related fatigue with dexamethasone: A double-blind, randomized, placebo-controlled trial in patients with advanced cancer. Journal of Clinical Oncology, 31, 3076–3082. 

Study Purpose

Compare the effect of dexamethasone and placebo on cancer-related fatigue (CRF) and quality of life.

Intervention Characteristics/Basic Study Process

Dexamethasone 4 mg or placebo orally twice a day for 14 days.

Sample Characteristics

  • N = 84
  • AVERAGE AGE: 60 years
  • MALES: 47%, FEMALES: 53%  
  • KEY DISEASE CHARACTERISTICS: Advanced multiple site-specific cancers: breast, lung, colon, prostate, other
  • OTHER KEY SAMPLE CHARACTERISTICS: Three or more concurrent signs/symptoms in past 24 hours with a 4 or greater score for severity on the symptom scale

Setting

  • SITE: Multi-site  
  • SETTING TYPE: Outpatient    
  • LOCATION: MD Anderson Cancer Center or Lyndon B. Johnson General Hospital

Phase of Care and Clinical Applications

  • PHASE OF CARE: Transition phase after active treatment
  • APPLICATIONS: Elder care, palliative care 

Study Design

  • Randomized, double-blinded, placebo-controlled trial

Measurement Instruments/Methods

  • Edmonton Symptom Assessment Scale (ESAS)
  • Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F)
  • Functional Assessment of Anorexia/Cachexia Therapy (FAACT)
  • Hospital Anxiety and Depression (HADS) questionnaire
  • NCI Common Toxicity Criteria (v.3.0)

Results

Dexamethasone and placebo groups had no differences in patient characteristics at baseline with the exception of more females in the dexamethasone group. Mean improvement scores of the FACIT-F subscale scores and ESAS physical distress scores were significantly better in the dexamethasone than the placebo group at days 8 (p = .005) and 15 (p = .008). ESAS pain was significantly better in the dexamethasone group on day 8. FAACT subscale scores were significantly better in the dexamethasone group on day 15. Fatigue did decline in both study groups. All other variables showed no significant differences in scores or frequency of adverse events.

Conclusions

Dexamethasone is more effective than placebo in improving CRF and quality of life in patients with advanced cancer.

Limitations

  • Small sample (< 100)
  • Key sample group differences that could influence results
  • Subject withdrawals were 10% or greater
  • Other limitations/explanation: Adherence to schedule and actual taking of dexamethasone was not reported. It was unclear why patients with gastrointestinal or head and neck cancers were grouped in reporting sample characteristics. Limited justification of dose or schedule choice for administration of dexamethasone. The dropout rate was 34/120 subjects, as noted in the manuscript, although a sample size listed in a table was 132 subjects.

Nursing Implications

A need exists for larger, long-term studies to determine safety and efficacy in patients with cancer (palliative care and active treatment). A significant number of patients with advanced cancer present with multiple signs and symptoms that may or may not benefit from dexamethasone therapy. Clinicians should be aware of barriers to adherence with dexamethasone.

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