RANDOMIZED EVALUATION OF CONTROLLED-RELEASE CODEINE AND PLACEBO IN CHRONIC CANCER PAIN

Codeine is widely wed in combination with acetaminophen and aspirin fa r the management of mild to moderate pain. However, there are few cont rolled 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 wit h cancer pain. Thirty-five patients with chronic cancer pain were rand omized in a double-blind crossover study to controlled-release (CR) co deine or placebo for 7 days each. Pain intensity was assessed at 0800 hr and 2000 hr using a visual analogue scab (VAS) and a five-point cat egorical scale, and the use of ''rescue'' acetaminophen-plus-codeins ( 300 mg/30 mg every 4 hr as needed) was recorded. Thirty patients compl eted 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 in tensity scores (22 +/- 18 mm versus 36 +/- 20 mm, P = 0.0001), categor ical pain intensity scares (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 da y. Daily ''rescue'' analgesic consumption was significantly lower on C R codeine, compared to placebo treatment (2.2 +/- 2.3 versus 4.6 +/- 2 .8 tablets per day, P = 0.0001). Both patients and investigators prefe rred CR codeine to placebo (80% versus 3%, P = 0.0014 and 73% versus 7 %, P = 0.0160, respectively). These data indicate that CR codeine, giv en every 12 hr results in significant reductions in pain intensity and the use of ''rescue'' acetaminophen-plus-codeine in patients with can cer pain. CR codeine provides the benefits of a flexible single entity codeine formulation and the convenience of 12-hr duration of action w hich allows patients uninterrupted sleep and improved compliance.