title: Efficacy and safety of fentanyl pectin nasal spray compared with immediate-release morphine sulfate tablets in the treatment of breakthrough cancer pain: a multicenter, randomized, controlled, double-blind, double-dummy multiple-crossover study.
abstract: BACKGROUND
  Immediate-release morphine sulfate (IRMS) remains the standard treatment for breakthrough cancer pain (BTCP), but its onset of effect does not match the rapid onset and short duration of most BTCP episodes.
  
  
  OBJECTIVE
  This study will evaluate the efficacy/tolerability of fentanyl pectin nasal spray (FPNS) compared with IRMS for BTCP.
  
  
  METHODS
  Patients (n = 110) experiencing one to four BTCP episodes/day while taking ≥ 60 mg/day oral morphine (or equivalent) for background cancer pain entered a double-blind, double-dummy (DB/DD), multiple-crossover study. Patients completing a titration phase (n = 84) continued to a DB/DD phase: 10 episodes of BTCP were randomly treated with FPNS and oral capsule placebo (five episodes) or IRMS and nasal spray placebo (5 episodes). The primary end point was pain intensity (P < .05 FPNS vs. IRMS) difference from baseline at 15 minutes (PID(15)). Secondary end points were onset of pain intensity (PI) decrease (≥ 1-point) and time to clinically meaningful pain relief (CMPR, ≥ 2-point PI decrease). Safety and tolerability were evaluated by adverse events (AEs) and nasal assessments. By-patient and by-episode analyses were completed.
  
  
  RESULTS
  Compared with IRMS, FPNS significantly improved mean PID(15) scores. 57.5% of FPNS-treated episodes significantly demonstrated onset of PI improvement by 5 minutes and 95.7% by 30 minutes. CMPR (≥ 2-point PI decrease) was seen in 52.4% of episodes by 10 minutes. Only 4.7% of patients withdrew from titration (2.4% in DB/DD phase) because of AEs; no significant nasal effects were reported.
  
  
  CONCLUSIONS
  FPNS was efficacious and well tolerated in the treatment of BTCP and provided faster onset of analgesia and attainment of CMPR than IRMS.
authors: Edinburgh Cancer Research Centre, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XR, UK. Marie.Fallon@ed.ac.uk
authors: Marie
authors: M
authors: Fallon
authors: Carlo
authors: C
authors: Reale
authors: Andrew
authors: A
authors: Davies
authors: A Eberhard
authors: AE
authors: Lux
authors: Kirushna
authors: K
authors: Kumar
authors: Andrzej
authors: A
authors: Stachowiak
authors: Rafael
authors: R
authors: Galvez
mesh_terms: D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D059390:Breakthrough Pain / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects / Q000627:therapeutic use*; D059085:Nasal Sprays; D009369:Neoplasms / Q000503:physiopathology*; D013607:Tablets
chemical_list: D000701:Analgesics, Opioid; D059085:Nasal Sprays; D013607:Tablets; D009020:Morphine; D005283:Fentanyl