title: Impact of Prophylactic Fentanyl Pectin Nasal Spray on Exercise-Induced Episodic Dyspnea in Cancer Patients: A Double-Blind, Randomized Controlled Trial.
abstract: Episodic breathlessness is common and debilitating in cancer patients.
  
  
  
  In this pilot study, we examined the effect of prophylactic fentanyl pectin nasal spray (FPNS) on exercise-induced dyspnea, physiologic function, and adverse events.
  
  
  
  In this parallel, double-blind randomized placebo-controlled trial, opioid-tolerant patients performed three six-minute walk tests (6MWTs) to induce dyspnea. They were randomized to receive either FPNS (15%-25% of total daily opioid dose each time) or placebo 20 minutes before the second and third 6MWTs. We compared dyspnea Numeric Rating Scale (NRS, 0-10, primary outcome), walk distance, vital signs, neurocognitive function, and adverse events between the first and second 6MWTs (T2-T1) and between the first and third 6MWTs (T3-T1).
  
  
  
  Twenty-four patients enrolled, with 96% completion. FPNS was associated with significant within-arm reduction in dyspnea NRS at rest (T2-T1: -0.9 [95% CI -1.7, -0.1]; T3-T1: -1.3 [95% CI -2.0, -0.5]) and at the end of a 6MWT (T2-T1: -2.0 [95% CI -3.5, -0.6]; T3-T1: -2.3 [95% CI -4.0, -0.7]), and longer walk distance (T2-T1 +23.8 m [95% CI +1.3, +46.2 m]; T3-T1: +23.3 m [95% CI -1.7, +48.2]). In the placebo arm, we observed no significant change in walk distance nor dyspnea NRS at rest, but significant reduction in dyspnea NRS at six minutes (T2-T1: -1.7 [95% CI -3.3, -0.1]; T3-T1: -2.5 [95% CI -4.2, -0.9]). Vital signs, neurocognitive function, and adverse effects did not differ significantly.
  
  
  
  FPNS was safe, reduced dyspnea at rest, and increased walk distance in before-after comparison. The placebo effect was substantial, which needs to be factored in future study designs.
  
  
  
  ClinicalTrials.govNCT01832402.
authors.affiliation: Department of Palliative Care and Rehabilitation Medicine, 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, M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Kilgore
authors.affiliation: Department of Biostatistics, M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Minjeong
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Palliative Care and Rehabilitation Medicine, M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Williams
authors.affiliation: Department of Biostatistics, M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Palliative Care and Rehabilitation Medicine, M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bruera
mesh_terms: D000281:Administration, Intranasal; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004417:Dyspnea / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D015444:Exercise / Q000502:physiology; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D059085:Nasal Sprays; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D010368:Pectins / Q000008:administration & dosage* / Q000009:adverse effects; D010865:Pilot Projects; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000070857:Walk Test
chemical_list: D000701:Analgesics, Opioid; D059085:Nasal Sprays; D010368:Pectins; D005283:Fentanyl
keywords: Dyspnea; exercise; nasal sprays; neoplasms; opioids; randomized controlled trial