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Journal of Clinical Oncology, Vol 23, No 7 (March 1), 2005: pp. 1586 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.239
Acetaminophen in Cancer PainDepartment of Palliative Care, Mater Health Services, Brisbane, Australia
Brisbane South Community Health Services, Brisbane, Australia
Department of Psychology, University of Sydney, Sydney, Australia To the Editor: A nonopioid (such as paracetamol or a nonsteroidal anti-inflammatory drug) was added as an essential component of step 2 of the revised version of the WHO analgesic ladder1 to reflect the relatively low analgesic potential of the "weak" opioids (codeine and dextropropoxyphene). This supports the use of combined preparations (eg, paracetamol/codeine and paracetamol/dextropropoxyphene). The use of paracetamol as an adjunct to "strong" opioids such as morphine is optional at step 3 of the WHO ladder but has become entrenched in palliative care "folklore," despite little evidence of its benefit. The article by Stockler et al2 is well designed and takes into account many of the problems inherent in palliative-care research (eg, the need for short study times, easy assessments, and telephone follow-up). The conclusion, however, that paracetamol improves pain in cancer patients already taking opioids is not well supported by the data presented. The only significant result in favor of adding paracetamol to the analgesic regimen was an average difference on two assessment days of 0.4 on an 11-point verbal numeric scale of pain (P = .03). One must question the clinical benefit of this. No other pain end point (Visual Analog Scale for pain, patient preference, and need for breakthrough medications) was statistically different. In addition, there was no difference in the balance between analgesia and adverse effects as measured by nausea and vomiting, drowsiness, and constipation scores. Although the average increase in overall well-being was just significant at the P = .05 level, this is arguably the softest outcome measure, as the determinants of well-being are multifactorial. The requirement of palliative patients to swallow an additional 10 large tablets a day for an uncertain clinical outcome may be considered a burdensome treatment. Certainly, in Australia, full compliance with this protocol would be problematic, as the public is well informed of the dangers to hepatic function with paracetamol doses exceeding 4 g/d. We consider that this study needs to be repeated in a larger number of patients and stratified according to the daily morphine-equivalent dose. Our hypothesis is that paracetamol may be of greater benefit to those on lower opioid doses, thus supporting the current WHO analgesic ladder recommendations. Authors’ Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES 1. World Health Organization: Cancer Pain Relief, With a Guide to Opioid Availability (ed 2), Geneva, Switzerland, World Health Organization, 1996
2. Stockler M, Vardy J, Pillai A, et al: Acetaminophen (Paracetamol) improves pain and well-being in people with advanced cancer already receiving a strong opioid regimen: A randomized, double-blind, placebo-controlled cross-over trial. J Clin Oncol 22:3389-3394, 2004
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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