Viola, R., Kiteley, C., Lloyd, N.S., Mackay, J.A., Wilson, J., Wong, R.K., & Supportive Care Guidelines Group of the Cancer Care Ontario Program in Evidence-Based Care. (2008). The management of dyspnea in cancer patients: A systematic review. Supportive Care in Cancer, 16(4), 329-337.

This systematic review evaluated the effectiveness of four drug classes (opioids, phenothiazines, benzodiazepines, and systemic corticosteroids) to relieve dyspnea experienced by patients with advanced cancer.

A criterion for inclusion in the review was a controlled trial involving the specified drug classes; however, trials were not limited to cancer except for corticosteroids.

The review identified three systematic reviews (one with meta-analysis), two practice guidelines, and 28 controlled studies.

• Outcomes were dyspnea measured by patient self-report, exercise tolerance, quality of life, and adverse events.
• Data were not pooled for opioid trials because of heterogeneity between trials but was pooled for benzodiazepines and phenothiazines.
• The review identified seven systemic studies that found a statistically significant beneficial effect of opioids on patient-reported breathlessness.
• None of the studies comparing nebulized morphine with placebo found it to be beneficial for relieving dyspnea.
• Controlled trials of benzodiazepines in patients without cancer did not show any benefit for treating dyspnea.
• Only two trials evaluating phenothiazines in patients without cancer were identified and showed conflicting results.

Systemic opioids, administered orally or parenterally, can be used to manage dyspnea in patients with cancer. Oral promethazine also may be used alone or in addition to systemic opioids. Nebulized morphine, prochlorperazine, and benzodiazepines are not recommended for the treatment of dyspnea, and promethazine must not be used parenterally because of the concern for serious tissue damage when administered intravenously.