• E Eisenberg, C S Berkey, D B Carr, F Mosteller, and T C Chalmers.
• Department of Neurology, Massachusetts General Hospital, Boston.
• J. Clin. Oncol. 1994 Dec 1; 12 (12): 2756-65.

PurposeTo assess the efficacy and safety of nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of cancer pain by meta-analyses of the published randomized control trials (RCTs).Patients And MethodsTwenty-five studies met inclusion criteria for analysis. Of these, 13 tested a single-dose effect, nine multiple-dose effects, and three both single- and multiple-dose effects of 16 different NSAIDs in a total of 1,545 patients. Baseline pain intensity (when provided) of moderate or higher was indicated in 81% of patients.ResultsSingle-dose NSAID studies found greater analgesic efficacy than placebo, with rough equivalence to 5 to 10 mg of intramuscular morphine. Pain scores differed insignificantly for aspirin versus three other NSAIDs. Analgesic responses to low- and high-dose NSAIDs suggested a dose-response relationship, but this was not statistically significant. Recommended and supramaximal single doses of three NSAIDs produced comparable changes in pain scores, which indicates a ceiling analgesic effect. Common side effects included upper gastrointestinal symptoms, dizziness, and drowsiness. The incidence of side effects showed a trend to increase with dose, without a ceiling effect, and to increase with multiple doses. Single or multiple doses of weak opioids (WO) alone or in combination (WO/C) with nonopioid analgesics did not produce greater analgesia than NSAIDs alone. Single doses of WO/C analgesics produced more side effects than NSAIDs alone, although both side effect incidence and patient dropout rates were equal when multiple doses were administered.ConclusionThese findings question whether the traditional World Health Organization (WHO) second analgesic step (addition of a weak opioid when pain is inadequately treated by a nonopioid analgesic alone) is warranted. A lack of comparable studies precluded testing the hypothesis that NSAIDs are particularly effective for malignant bone pain.

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