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Nonsteroidal Anti-Inflammatory Drugs, Alone or Combined With Opioids, for Cancer Pain

A Systematic Review

From the Department of Anesthesia and Division of Clinical Care Research, New England Medical Center and Tufts University School of Medicine, Boston, MA; and Department of Pharmacy, University of Washington, Seattle, WA.

Address reprint requests to Ewan McNicol, RPh, Department of Pharmacy, New England Medical Center, Box 420, 750 Washington St, Boston, MA 02111; e-mail: EMcNicol{at}tufts-nemc.org

PURPOSE: To assess the safety and efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs), alone or combined with opioids, for the treatment of cancer pain.

PATIENTS AND METHODS: Forty-two trials involving 3,084 patients met inclusion criteria: eight compared NSAID with placebo; 13 compared one NSAID with another; 23 compared NSAID with opioid, NSAID or opioid versus NSAID plus opioid combinations, or NSAID plus opioid combinations versus NSAID plus opioid combinations; and nine studies assessed the effect of increasing NSAID dose.

RESULTS: Sixteen studies lasted 1 week or longer and 11 evaluated a single dose. Seven of eight trials demonstrated superior efficacy of single doses of NSAID compared with placebo. Only four of 13 studies reported increased efficacy of one NSAID compared with another; four other studies found that one NSAID had fewer side effects than one or more others. Thirteen of 14 studies found no difference, or minimal clinical difference, when comparing an NSAID plus opioid combination versus either drug alone. Comparisons between various NSAID plus opioid combinations were inconclusive. Four studies demonstrated increased efficacy with increased NSAID dose, without dose-dependent increases in side effects.

CONCLUSION: Heterogeneity of study methods and outcomes precluded meta-analyses. Short duration of studies undermines generalization of findings on efficacy and safety. On the basis of limited data, NSAIDs appear to be more effective than placebo for cancer pain; clear evidence to support superior safety or efficacy of one NSAID compared with another is lacking; and trials of combinations of an NSAID with an opioid have disclosed either no significant difference, or at most a slight but statistically significant advantage, compared with either single entity.

Supported in part by the AHRQ under contract 290-07-0019 and sustained through funding from the Richard Saltonstall Charitable Foundation and the Evenor Armington Fund.

This article is an updated, expanded version of a section of an Agency for Healthcare and Research Quality (AHRQ) report (Goudas L, Carr DB, Bloch R, et al: Management of cancer pain: Evidence Report/Technology Assessment No. 35 [prepared by the New England Medical Center Evidence-Based Practice Center under contract No. 290-97-0019], AHRQ Publication 02-E002, Rockville, MD, AHRQ, October 2001).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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