Effect of prophylactic fentanyl buccal tablet (FBT) on exertional dyspnea in patients with cancer: A pilot double-blind, placebo-controlled, randomized trial.

Abstract

10085 Background: Exertional dyspnea is one of the most common, debilitating and difficult-to-treat symptoms in cancer patients. Few clinical trials have been conducted. We tested the hypothesis that FBT, a rapid onset opioid, given prophylactically prior to exertion can improve exertional dyspnea. Methods: In this double-blind parallel (1:1) RCT, we asked cancer patients who were opioid-tolerant and had exertional dyspnea to complete a 6 minute walk test (6MWT) at baseline, and then randomly assigned them to either FBT proportional to 20-50% of daily dose or placebo 30 minutes before a second 6MWT. The primary outcome was a validated 11-point dyspnea NRS assessing dyspnea “now” (where 0 = none and 10 = worst possible) every minute during each 6MWT. Secondary outcomes included walk distance, vital signs and neurocognitive testing, adverse effects, and global impression. Ten evaluable patients in the FBT provided 80% power to detect an effect size as small as 1.0 using a two-sided paired t-test with a significance level of 5% to compare the change of dyspnea between the first and second walk tests. We compared the outcomes between the first and second 6MWTs using paired t-test. Results: Among 22 patients enrolled, 20 (91%) completed the study (9 FBT, 11 placebo). FBT was associated with a significant within-arm reduction in dyspnea NRS between 0 and 6 minutes (mean change -2.4, 95% confidence interval [CI] -3.5, -1.3) and respiratory rate (mean change -2.6, 95% CI -4.7, -0.4). Placebo was also associated with a non-statistically significant decrease in dyspnea (mean change -1.1). Between arm comparison of dyspnea scores in the second 6MWT favored FBT, albeit not statistically significant (estimate -0.25, P = 0.068). Global impression revealed more patients in the FBT group than placebo group reporting their dyspnea was at least “somewhat better” in the second 6MWT (4/9 vs. 0/11, P = 0.03). The other secondary outcomes did not differ significantly between arms. Conclusions: These data support our hypothesis that proportionally dosed FBT was associated with improvement in exertional dyspnea, and highlights the need for larger confirmatory trials. Clinical trial information: NCT01856114.