Adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison to long-acting morphine: a meta-analysis and systematic review of the literature

To assess the adverse effects of transdermal opiates treating moderate-severe cancer pain in comparison with slow release oral morphine. A systematic review of the literature in the MEDLINE and EMBASE databases from 1966 to June 2007 was independently performed by two authors. All phase 3 randomized trials comparing transdermal opiates and slow-release oral morphine in the treatment of moderate-severe cancer pain were considered eligible and included in the analysis. The primary end point was the overall adverse effects odds ratio (OR); secondary end points were the overall gastrointestinal adverse effects, constipation, nausea, somnolence, patients' preference, and trial withdrawal. Heterogeneity was analyzed using the Mantel-Haenszel test, and outcome analysis was performed using a random effect model; an alpha error lower than 5% was assumed as statistically significant. Four trials met the selection criteria. The safety of transdermal opiates (fentanyl and buprenorphine) and slow-release oral morphine was analyzed in 425 patients. A significant difference in favor of transdermal opiates was observed for constipation (OR=0.38, p