title: A titration strategy is needed to manage breakthrough cancer pain effectively: observations from data pooled from three clinical trials.
abstract: BACKGROUND
  Breakthrough pain is a prevalent and serious problem in patients with cancer. However, it is not known how best to predict the effective dose of breakthrough opioid for any given patient.
  
  
  METHODS
  Data were pooled and reanalyzed from three large, randomized clinical trials of the rapidly absorbed oral transmucosal fentanyl citrate lozenges (OTFC) in which patients were carefully titrated to an optimal OTFC dose. The relationships between the optimal OTFC dose, patients' previous opioid dose, 24-hour total opioid, and patient characteristics were explored to determine whether the optimal OTFC dose can be predicted based on pretreatment clinical factors.
  
  
  RESULTS
  The cohort included 188 patients within the three trials whose breakthrough pain was effectively managed with OTFC. Prior to entry into the trial, the average breakthrough opioid dose in the 188 patients was 12% of the daily dose of scheduled opioid but strikingly, ranged from 1%-72%. The optimal OTFC dose was poorly correlated with patients' scheduled or previous breakthrough opioid doses. The only clinically meaningful correlation was that the average final OTFC dose significantly decreased with increasing age. Overall, there was enormous interindividual variability in patients' dose requirements for breakthrough pain.
  
  
  CONCLUSIONS
  This is the largest study to date of the relationship between clinical variables and the effective dose of OTFC when titrated to effect for breakthrough cancer pain. These results suggest that use of breakthrough medication should routinely be individualized with a titration strategy separate from the around-the-clock medication, according to each patient's response to their breakthrough opioid.
authors.affiliation: Department of Medicine, Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, Alberta, Canada. neilha@cancerboard.ab.ca
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hagen
authors.forename: Kim
authors.initials: K
authors.lastname: Fisher
authors.forename: Charlemaigne
authors.initials: C
authors.lastname: Victorino
authors.forename: John T
authors.initials: JT
authors.lastname: Farrar
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D017186:Titrimetry / Q000379:methods
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl