Effects of prophylactic subcutaneous fentanyl on exercise-induced breakthrough dyspnea in cancer patients: A preliminary double-blind, randomized, controlled trial

Context Dyspnea is one of the most distressing symptoms in patients with cancer, and often worsens with breakthrough episodes on exertion. We hypothesized that fentanyl given prophylactically may alleviate breakthrough dyspnea. Objectives To determine the feasibility of conducting a randomized trial of subcutaneous fentanyl in patients with cancer, and examine the effects of fentanyl on dyspnea, walk distance, vital signs, and adverse events. Methods In this double-blind, randomized, controlled trial, we asked ambulatory patients with breakthrough dyspnea to perform a baseline six minute walk test (6MWT), and then assigned them to either subcutaneous fentanyl or placebo 15 minutes before a second 6MWT. We documented the change in dyspnea Numeric Rating Scale (NRS) score, walk distance, vital signs, and adverse events between the first and second 6MWT. Results A total of 20 patients were enrolled (1:1 ratio) without attrition. Comparison between baseline and second walk showed that fentanyl was associated with significant improvements in dyspnea NRS score at the end of the 6MWT (mean [95% CI] -1.8 [-3.2, -0.4]), dyspnea NRS score at rest of 15 minutes after drug administration (-0.9 [-1.8, -0.04]), Borg Scale fatigue score at the end of the 6MWT (-1.3 [-2.4, -0.2]), 6MWT distance (+37.2 m [5.8, 68.6]), and respiratory rate (-2.4 [-4.5, -0.3]). Nonstatistically significant improvements also were observed in the placebo arm, with no difference between the two study arms. No significant adverse effects were observed. Conclusion Prophylactic fentanyl was safe and improved dyspnea, fatigue, walk distance, and respiratory rate. We also observed a large placebo effect. Our results justify larger randomized controlled trials with higher fentanyl doses (clinicaltrials.gov registration: NCT01515566).