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Looking for the Role of NSAIDs in Cancer Pain

Anestehsia & Intensiva Care Unit, Pain Relief & Palliative Care Unit, La Maddalena Cancer Center, Palermo, Italy

To the Editor:

We greatly appreciated the review article on the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in cancer pain.¹ This subject remains controversial in the literature,² because the results presented overlap, in some ways, with those already presented 10 years ago.

The content and the conclusion of this article, however, deserve some comments. The principal limitation observed by the authors was the short duration typical of most studies. Because cancer pain has a dynamic course, it is necessary to have a repeated assessment to correctly evaluate the possible clinical advantage of NSAIDs, though concomitant and multiple variables may occur to confound the picture. One other question is whether increasing the opioid dose would allow similar results without adding a second agent. Finally, no substantial data exist to claim the use of NSAIDs for some specific pain mechanism.

Surprisingly, some long-term studies with a clear practical and clinical intent, which specifically assessed such unresolved questions, were not reported. Despite the relatively low number of patients recruited, clinically significant information can be drawn. An initial better analgesia and a slower opioid escalation was observed in patients receiving ketorolac, in comparison with patients treated with opioids alone. Each group presented a different adverse effect pattern (constipation for the group treated by opioids only, and gastric discomfort for the group receiving the combination of analgesics). Interestingly, in patients starting with lower doses of morphine, the addition of ketorolac and adjuvant drugs was more expensive than using morphine and adjuvants. However, these differences disappeared in patients who were administered higher doses of morphine.³ The conclusions of this study are intriguing, because the reluctance of North American physicians to use NSAIDs, and conversely, the extensive and sometime exaggerated use of NSAIDs in European countries, may find a compromise based on the data pointed out in this work. For example, patients could start by receiving opioids alone, and then add NSAIDs to their treatment regimen, for conditions in which pain is particularly sensitive to NSAIDs, or to reduce the tendency to further opioid escalation, when adverse effects tend to develop. Visceral pain or any multiple pain mechanism seemed to be equally sensitive to NSAIDs.³ In a study controlled for "mechanism", the few patients who had a sole and distinguishable pain type, at least at study admission, had visceral pain and somatic pain due to bone metastases that were equally sensitive to the use of NSAIDs when NSAID therapy was added to opioids in a period of 2 weeks. Again, NSAIDs offered a consistent improvement in opioid analgesia, with a minimal need of opioid dose increments. On the other hand, physicians really know that NSAIDs may offer a potent analgesia in individuals who show a particular sensitivity to these drugs, which can never be reached, even with increasing doses of opioids, unless producing disastrous adverse effects.

Although we agree that more studies are necessary to demonstrate the safety of long-term use of NSAIDs, particularly for a population at high risk, such as cancer patients, available studies may help to gather better information on the role of NSAIDs in cancer pain, avoiding extreme position (yes or not), based on prejudice or incomplete information.

Author's Disclosures of Potential Conflicts of Interest

The author indicated no potential conflicts of interest.

REFERENCES

1. McNicol E, Strassels S, Goudas L, et al: Nonsteroidal anti-inflammatory drugs, alone or combined with opioids, for cancer pain: A systematic review. J Clin Oncol 22:1975-1992, 2004[Abstract/Free Full Text]

2. Eisenberg E, Berkey C, Carr D, et al: Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: A meta-analysis. J Clin Oncol 12:2756-2765, 1994[Abstract/Free Full Text]

3. Mercadante S, Fulfaro F, Casuccio A: A randomized controlled study on the use of anti-inflammatory drugs in patients with cancer pain on morphine therapy: Effects on dose-escalation and a pharmacoeconomic analysis. Eur J Cancer 38:1358-1363, 2002

4. Mercadante S, Casuccio A, Agnello A, et al: Analgesic effects of nonsteroidal anti-inflammatory drugs in cancer pain due to somatic or visceral mechanism. J Pain Symptom Manage 17:351-356, 1999[CrossRef][Medline]

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• In Reply:
  Ewan McNicol and Daniel B. Carr
  JCO 2005 23: 2443 [Full Text]

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