Prophylactic Fentanyl Sublingual Spray for Episodic Exertional Dyspnea in Cancer Patients: A Pilot Double-Blind Randomized Controlled Trial

Abstract Context The optimal dose of fentanyl sublingual spray (FSS) for exertional dyspnea has not been determined. Objective We examined the effect of two doses of prophylactic FSS on exertional dyspnea. Methods In this parallel, dose-finding, double-blind randomized clinical trial, opioid-tolerant cancer patients completed a shuttle walk test at baseline. Patients completed a second shuttle walk test 10 minutes after a single dose of FSS equivalent to either 35-45% (high dose) or 15-25% (low dose) of the total daily opioid dose. The primary outcome was change in modified dyspnea Borg scale (0-10) between the first and second shuttle walk tests. Secondary outcomes included adverse events as well as changes in walk distance, vital signs, and neurocognitive function. Results Thirty of the 50 enrolled patients completed the study. High dose FSS (n=13) resulted in significantly lower dyspnea (mean change -1.42; 95% CI -2.37, -0.48; P=0.007) and greater walk distance (mean change 44 m; P=0.001) compared to baseline. Low dose FSS (n=17) resulted in a non-significant reduction in dyspnea (mean change -0.47; 95% CI -1.26, 0.32; P=0.24) and significant increase in walk distance (mean change 24 m; P=0.01) compared to baseline. Global evaluation showed high dose group was more likely to report at least somewhat better improvement (64% vs. 24%; P=0.06). No significant adverse events or detriment to vital signs or neurocognitive function were detected. Conclusions Prophylactic FSS was well tolerated and demonstrated a dose-response relationship in improving both dyspnea and walk distance. High dose FSS should be tested in confirmatory trials.