Interventions for Breathlessness in Patients With Advanced Cancer

Main Points

For patients with advanced cancer:

• Airflow interventions (fans) were more effective for improving breathlessness compared with usual care or sham.
• Bilevel ventilation (a form of noninvasive positive pressure ventilation) was more effective than standard supplemental oxygen for improving breathlessness.
• Acupressure/reflexology were more effective than usual care or sham for improving breathlessness.
• Neither behavioral/psychoeducational interventions alone nor activity/rehabilitation interventions alone were more effective than usual care for improving breathlessness. However, multicomponent nonpharmacological interventions that combined these, with integrative medicine interventions, were more effective than usual care for improving breathlessness.
• Opioids were not more effective than placebo or anxiolytics for improving breathlessness or exercise capacity; most of these studies in advanced cancer were of exertional breathlessness. Studies on opioids showed no differences in effectiveness between different doses or routes of administration for improving breathlessness.
• Anxiolytics were not more effective than placebo for improving breathlessness.
• Both nonpharmacological and pharmacological interventions led to adverse event-related dropouts in a small percentage of patients.

Structured Abstract

Objectives. To assess benefits and harms of nonpharmacological and pharmacological interventions for breathlessness in adults with advanced cancer.

Data sources. We searched PubMed®, Embase®, CINAHL®, ISI Web of Science, and the Cochrane Central Register of Controlled Trials through early May 2020.

Review methods. We included randomized controlled trials (RCTs) and observational studies with a comparison group evaluating benefits and/or harms, and cohort studies reporting harms. Two reviewers independently screened search results, serially abstracted data, assessed risk of bias, and graded strength of evidence (SOE) for key outcomes: breathlessness, anxiety, health-related quality of life, and exercise capacity. We performed meta-analyses when possible and calculated standardized mean differences (SMDs).

Results. We included 48 RCTs and 2 retrospective cohort studies (4,029 patients). The most commonly reported cancer types were lung cancer and mesothelioma. The baseline level of breathlessness varied in severity. Several nonpharmacological interventions were effective for breathlessness, including fans (SMD -2.09 [95% confidence interval (CI) -3.81 to -0.37]) (SOE: moderate), bilevel ventilation (estimated slope difference -0.58 [95% CI -0.92 to -0.23]), acupressure/reflexology, and multicomponent nonpharmacological interventions (behavioral/psychoeducational combined with activity/rehabilitation and integrative medicine). For pharmacological interventions, opioids were not more effective than placebo (SOE: moderate) for improving breathlessness (SMD -0.14 [95% CI -0.47 to 0.18]) or exercise capacity (SOE: moderate); most studies were of exertional breathlessness. Different doses or routes of administration of opioids did not differ in effectiveness for breathlessness (SOE: low). Anxiolytics were not more effective than placebo for breathlessness (SOE: low). Evidence for other pharmacological interventions was limited. Opioids, bilevel ventilation, and activity/rehabilitation interventions had some harms compared to usual care.

Conclusions. Some nonpharmacological interventions, including fans, acupressure/reflexology, multicomponent interventions, and bilevel ventilation, were effective for breathlessness in advanced cancer. Evidence did not support opioids or other pharmacological interventions within the limits of the identified studies. More research is needed on when the benefits of opioids may exceed harms for broader, longer term outcomes related to breathlessness in this population.