title: Effects of prophylactic subcutaneous fentanyl on exercise-induced breakthrough dyspnea in cancer patients: a preliminary double-blind, randomized, controlled trial.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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 (+37.2m [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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: Department of Palliative Care and Rehabilitation Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. Electronic address: dhui@mdanderson.org.
authors.forename: David
authors.initials: D
authors.lastname: Hui
authors.affiliation: Department of Palliative Care and Rehabilitation Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Palliative Care and Rehabilitation Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Frisbee-Hume
authors.affiliation: Department of Biostatistics, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Chisholm
authors.affiliation: Department of Palliative Care and Rehabilitation Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Morgado
authors.affiliation: Department of Palliative Care and Rehabilitation Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Reddy
authors.affiliation: Department of Palliative Care and Rehabilitation Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bruera
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D015444:Exercise; D005080:Exercise Test; D005221:Fatigue / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D005240:Feasibility Studies; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D015990:Placebo Effect; D056152:Respiratory Rate / Q000187:drug effects; D012146:Rest; D012720:Severity of Illness Index; D065566:Subcutaneous Absorption; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl
keywords: Dyspnea; exercise; fentanyl; neoplasms; opioids; prophylaxis; randomized controlled trial; subcutaneous