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Two or more alternative routes of opioid application were compared in 18 papers with a total of 674 patients. The best evidence base was available for the subcutaneous route. A comparison of subcutaneous and intravenous routes found no differences, confirming both routes as feasible, effective and safe. Efficacy and safety of the rectal route was comparable to the parenteral route. The side effect profile seemed to be very similar for the subcutaneous, intravenous, rectal or transdermal routes. Local side effects were reported for rectal application as well as for subcutaneous and transdermal administration. In conclusion, the systematic review found good evidence that subcutaneous administration of morphine or other opioids is an effective alternative for cancer patients if oral treatment is not possible. However, for a number of patients intravenous, rectal or transdermal therapy will offer a good alternative to the subcutaneous route. 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