title: How to switch from morphine or oxycodone to methadone in cancer patients? a randomised clinical phase II trial.
abstract: OBJECTIVE
  Opioid switching is a treatment strategy in cancer patients with unacceptable pain and/or adverse effects (AEs). We investigated whether patients switched to methadone by the stop and go (SAG) strategy have lower pain intensity (PI) than the patients switched over three days (3DS), and whether the SAG strategy is as safe as the 3DS strategy.
  
  
  METHODS
  In this prospective, open, parallel-group, multicentre study, 42 cancer patients on morphine or oxycodone were randomised to the SAG or 3DS switching-strategy to methadone. The methadone dose was calculated using a dose-dependent ratio. PI, AEs and serious adverse events (SAEs) were recorded daily for 14 days. Primary outcome was average PI day 3. Secondary outcomes were PI now and AEs day 3 and 14 and number of SAEs.
  
  
  RESULTS
  Twenty one patients were randomised to each group, 16 (SAG) and 19 (3DS) patients received methadone. The mean preswitch morphine doses were 900 mg/day in SAG and 1330 mg/day in 3DS. No differences between groups were found in mean average PI day 3 (mean difference 0.5 (CI -1.2-2.2); SAG 4.1 (CI 2.3-5.9) and 3DS 3.6 (CI 2.9-4.3) or in PI now. The SAG group had more dropouts and three SAEs (two deaths and one severe sedation). No SAEs were observed in the 3DS group.
  
  
  CONCLUSIONS
  The SAG patients reported a trend of more pain, had significantly more dropouts and three SAEs, which indicate that the SAG strategy should not replace the 3DS when switching from high doses of morphine or oxycodone to methadone.
authors.affiliation: Pain and Palliation Research Group, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. kristin.moksnes@ntnu.no
authors.forename: K
authors.initials: K
authors.lastname: Moksnes
authors.forename: O
authors.initials: O
authors.lastname: Dale
authors.forename: J H
authors.initials: JH
authors.lastname: Rosland
authors.forename: O
authors.initials: O
authors.lastname: Paulsen
authors.forename: P
authors.initials: P
authors.lastname: Klepstad
authors.forename: S
authors.initials: S
authors.lastname: Kaasa
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D057915:Drug Substitution / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D009369:Neoplasms / Q000150:complications*; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010352:Patient Dropouts; D011446:Prospective Studies
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; D010098:Oxycodone; D008691:Methadone