title: Randomized evaluation of controlled-release codeine and placebo in chronic cancer pain.
abstract: Codeine is widely used in combination with acetaminophen and aspirin for the management of mild to moderate pain. However, there are few controlled clinical trials of single-entity codeine in chronic cancer pain. The purpose of this study was to evaluate the clinical efficacy and safety of controlled-release codeine given every 12 hr in patients with cancer pain. Thirty-five patients with chronic cancer pain were randomized in a double-blind crossover study to controlled-release (CR) codeine or placebo, for 7 days each. Pain intensity was assessed at 0800 hr and 2000 hr using a visual analogue scale (VAS) and a five-point categorical scale, and the use of "rescue" acetaminophen-plus-codeine (300 mg/30 mg every 4 hr as needed) was recorded. Thirty patients completed the study (17 male, 13 female; mean age, 64.4 +/- 9.8 years) with a mean daily CR codeine dose of 277 +/- 77 mg (range, 200-400 mg). CR codeine treatment resulted in significantly lower overall VAS pain intensity scores (22 +/- 18 mm versus 36 +/- 20 mm, P = 0.0001), categorical pain intensity scores (1.2 +/- 0.8 versus 1.8 +/- 0.8, P = 0.0001), and pain scores when assessed by day of treatment and by time of day. Daily "rescue" analgesic consumption was significantly lower on CR codeine, compared to placebo treatment (2.2 +/- 2.3 versus 4.6 +/- 2.8 tablets per day, P = 0.0001). Both patients and investigators preferred CR codeine to placebo (80% versus 3%, P = 0.0014 and 73% versus 7%, P = 0.0160, respectively). These data indicate that CR codeine, given every 12 hr results in significant reductions in pain intensity and the use of "rescue" acetaminophen-plus-codeine in patients with cancer pain. CR codeine provides the benefits of a flexible single entity codeine formulation and the convenience of 12-hr duration of action, which allows patients uninterrupted sleep and improved compliance.
authors.affiliation: Department of Medical Oncology, Thunder Bay Regional Cancer Centre, Ontario, Canada.
authors.forename: H S
authors.initials: HS
authors.lastname: Dhaliwal
authors.forename: P
authors.initials: P
authors.lastname: Sloan
authors.forename: W W
authors.initials: WW
authors.lastname: Arkinstall
authors.forename: M P
authors.initials: MP
authors.lastname: Thirlwell
authors.forename: N
authors.initials: N
authors.lastname: Babul
authors.forename: Z
authors.initials: Z
authors.lastname: Harsanyi
authors.forename: A C
authors.initials: AC
authors.lastname: Darke
mesh_terms: D000368:Aged; D002908:Chronic Disease; D003061:Codeine / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D010919:Placebos; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D010919:Placebos; D003061:Codeine