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.
Objective the role of benzodiazepines in relieving dyspnea in patients with cancer has not yet been established. This systematic review and meta-analysis aimed to determine the efficacy and safety of benzodiazepines alone or in combination with opioids for dyspnea in patients with cancer. Methods Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Ichushi-Web were searched for articles published from database inception to 23 September 2019. Studies of benzodiazepines alone or in combination with opioids for dyspnea were included. The primary outcome measure was the relief of dyspnea. The secondary outcome measures were anxiety, somnolence and severe adverse events. Results of 505 publications initially identified, two trials and one trial were included in the meta-analysis of midazolam alone and in combination with morphine, respectively. With regard to the relief of dyspnea, midazolam alone showed no significant difference compared with morphine alone, with a relative risk of 0.95 (95% confidence interval: 0.47–1.89). Meanwhile, midazolam plus morphine was significantly more effective than morphine alone, with a relative risk of 1.33 (95% confidence interval: 1.02–1.75). For anxiety relief, a meta-analysis could not be performed because of insufficient data. The incidence of somnolence and severe adverse events was not significantly different between the experimental and control groups for either midazolam alone or in combination with morphine. Conclusions benzodiazepines alone do not significantly improve dyspnea compared with opioids alone, but a combination of benzodiazepines and opioids may be more effective. Evidence from randomized controlled trials focusing on patients with cancer has not been generated in recent years. Further appropriately designed randomized controlled trials are required.
Pain control becomes poor in some cases after opioid switching from oxycodone tablet (OXC) to fentanyl patch (FP). However, fewer studies on risk factors have been reported. In this study, we surveyed the states of pain control (PC) and opioid administration, patient background, laboratory test values, and concomitant drugs retrospectively in 86 patients switching from OXC to FP between June 2010 and April 2018 in Mazda Hospital and Hiroshima Prefectural Hospital. The subjects were divided into 2 groups based on the median number of days to the initial dose increase after switching to FP. Between the early (<7.5 d) and late (≥7.5 d) increase groups, a significant difference was noted in the presence or absence of liver metastasis (LM), concomitant drugs with a high protein binding rate (CDHPBR), and the state of PC before and after switching to FP (p < 0.05). Binary logistic regression analysis showed the presence of CDHPBR, absence of LM, and poor PC after switching were risk factors for early dose increase (presence of CDHPBR: odds ratios (OR), 3.30, 95% confidence interval (CI), 1.09-9.98; presence of LM: OR, 0.31, 95% CI, 0.10-0.93; good PC: OR, 0.23, 95% CI, 0.07-0.79, respectively). The initial dose increase after switching to FP was earlier in patients with CDHPBR and/or without LM than those without CDHPBR and with LM (p < 0.05, log-rank test). It was suggested that the analgesic effect of FP after switching from OXC is likely to be insufficient in patients treated with CDHPBR and patients without LM.
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