Opioids for the management of dyspnea in cancer patients: a systematic review and meta-analysis

Abstract

Dyspnea is a prevalent symptom that significantly reduces quality of life of cancer patients. Palliative treatment is necessary when the symptoms do not respond to treatment for their cause. Opioids are widely used as pharmacological therapy, but evidence for individual agents is inconsistent. The purpose of this study was to evaluate the efficacy and safety of opioids for dyspnea in cancer patients. We searched the CENTRAL, MEDLINE, EMBASE, and ICHUSHI for studies using opioids for dyspnea in adult cancer patients reported by September 2019. Screening of the retrieved literature and assessment of risk of bias and outcomes were performed by two independent authors. A meta-analysis was performed on the primary endpoint, relief of dyspnea, and secondary endpoints including quality of life, somnolence as a side effect, and serious adverse events. Twelve randomized controlled trials were evaluated regarding relief of dyspnea. Somnolence and serious adverse events were evaluated in seven and four randomized controlled trials, respectively, but no randomized controlled trials were evaluable for quality of life. Overall, opioids were more effective than placebo for dyspnea (standardized mean difference - 0.43, 95% confidence interval [CI] - 0.75 to - 0.12). Although significant difference was found between systemic morphine and placebo in the drug-specific analysis, no significant difference could be detected in the other analyses. Systemic administration of opioids is more effective than placebo in relieving dyspnea in cancer patients. Robust evidence on the efficacy and safety of opioids on dyspnea in cancer patients is lacking, and further studies are needed.

Keywords: Cancer; Dyspnea; Meta-analysis; Opioid; Systematic review.

Fig. 1

PRISMA 2020 flow diagram of the study

Fig. 2

Bias risks of selected randomized controlled studies. ITT, intention-to-treat. The left side shows the distribution of the studies by bias, and the right side details the risk of bias for each individual study

Fig. 3

Forest plots for palliation of dyspnea. CI confidence interval, IV inverse variance, SD standard deviation, Std standard. Mean and SD represent the dyspnea measures; Total represents the number of patients; Experimental and Control represent the opioid intervention and placebo, respectively

Fig. 4

Forest plots for palliation of dyspnea for the morphine subgroup. CI confidence interval; IV inverse variance, SD standard deviation, Std standard. Mean and SD represent the dyspnea measures; Total represents the number of patients; Experimental corresponds to morphine and Control represents placebo or active control

Fig. 5

Forest plots for palliation of dyspnea for the fentanyl subgroup. CI confidence interval, IV inverse variance, SD standard deviation, Std standard. Mean and SD represent the dyspnea measures; Total represents the number of patients; Experimental corresponds to fentanyl and Control represents placebo or active control

Fig. 6

Forest plots for somnolence. CI confidence interval, M-H Mantel–Haenszel. Events and Total represents the number of patients; Experimental corresponds to opioids and Control represents placebo or active control

Fig. 7

Forest plots for somnolence for the morphine subgroup. CI confidence interval, M-H Mantel–Haenszel. Events and Total represents the number of patients; Experimental corresponds to morphine and Control represents placebo or active control

Fig. 8

Forest plots for somnolence for the fentanyl subgroup. CI confidence interval, M-H Mantel–Haenszel. Events and Total represents the number of patients; Experimental corresponds to fentanyl and Control represents placebo

Fig. 9

Forest plot for severe adverse events. CI confidence interval, M-H Mantel–Haenszel. Events and Total represents the number of patients; Experimental corresponds to opioids and Control represents placebo or active control