Cochrane for Clinicians

Putting Evidence into Practice

NSAIDs Alone or with Opioids as Therapy for Cancer Pain

MICHAEL B. POTTER, M.D., Department of Family and Community Medicine, University of California, San Francisco, School of Medicine, San Francisco, California

The Cochrane Abstract below is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Michael B. Potter, M.D., presents a clinical scenario and question based on the Cochrane Abstract, followed by an evidence-based answer and a full critique of the review.

This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). EB CME is clinical content presented with practice recommendations supported by evidence that has been reviewed systematically by an AAFP-approved source. The practice recommendations in this activity are available online at http://www.cochrane.org/cochrane/revabstr/AB005180.htm.

Clinical Scenario

A 70-year-old woman is diagnosed with malignant melanoma that has metastasized to the liver and lungs. She has begun to experience abdominal pain, which you attribute to the liver metastases. She wants to know what you recommend for pain management.

Clinical Question

What is the most effective therapy for the management of cancer pain?

Evidence-Based Answer

Short-term trials indicate that cancer pain can be reduced with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) as initial monotherapy. NSAIDs combined with opioids can result in slight short-term improvement in pain compared with either agent alone. Long-term efficacy and safety of NSAIDs for cancer pain have not been established.1

Practice Pointers

The World Health Organization's (WHO's) three-step analgesic ladder is a widely accepted framework for treating cancer pain.2 According to the WHO approach, treatment for mild cancer pain can begin with analgesics such as acetaminophen or NSAIDs. For patients in moderate pain, weak or episodic short-acting opioids can be added. For severe intractable cancer pain, more potent long-acting opioids are recommended. Adjuvant analgesics or therapies can be added at any point, and should be individualized according to the underlying cause of pain, the patient's desires, and the available resources. For example, antidepressants and anticonvulsants commonly are prescribed for neuropathic pain. Corticosteroids have been used in a wide range of cancer pain syndromes. Radiotherapy and bisphosphonates may palliate bone metastases. Surgery and chemotherapy may palliate pain caused by tumor growth and encroachment on normal structures. A variety of physical and psychologic modalities also may be helpful adjuncts for cancer pain.

The main effect of the WHO guidelines has been to facilitate more liberal use of opioid therapy in cancer patients with intractable pain.3 However, there still is concern that opioids are underused or ineffectively prescribed for cancer pain.3,4 The National Cancer Institute Web site (http://www.cancer.gov/cancertopics/pdq/supportivecare/pain) provides regularly updated information for health care professionals and their patients on the most common therapeutic options for the relief of cancer pain.

According to the results of the Cochrane review,1 NSAIDs should not be overlooked as a potential first-line treatment for cancer pain. They may provide additive pain relief for some patients who already are receiving opioids for moderate to severe cancer pain. Caution should be used in interpreting these results. Most studies reviewed were small and heterogeneous in terms of type of cancer or cancer pain, level of pain among participants, and specific medications used. In addition, none of the studies lasted more than two weeks, so potential adverse effects from prolonged use of these treatments individually or in combination could not be assessed or compared. Although it is possible that NSAIDs could be better tolerated than opioids in some situations, there certainly are situations in which the opposite is true. Therefore, it still is left to the physician to determine which therapies to offer each patient on an individual basis.

The initial objectives of this review included determining the benefit of acetaminophen in treating cancer pain, but the authors were unable to find sufficient good-quality studies to analyze acetaminophen separately from NSAIDs. However, a recent randomized trial,5 published shortly after this review, demonstrated improved pain control with acetaminophen in patients with advanced cancer who already were receiving a strong opioid regimen. Like the NSAID studies, the sample size was small, the duration of the study brief, and improvement in pain scores modest.

The Author

Michael B. Potter, M.D., is an associate clinical professor in the Department of Family and Community Medicine at the University of California, San Francisco, School of Medicine.

Address correspondence to Michael B. Potter, M.D., Department of Family and Community Medicine, University of California, San Francisco, San Francisco, CA 94143-0900 (e-mail: potterm@fcm.ucsf.edu). Reprints are not available from the author.

REFERENCES

1. McNicol E, Strassels SA, Goudas L, Lau J, Carr DB. NSAIDs or paracetamol, alone or combined with opioids, for cancer pain. Cochrane Database Syst Rev 2005;(2):CD005180.

2. World Health Organization: Cancer pain relief. 2d ed. Geneva, Switzerland: World Health Organization, 1996.

3. Meldrum M. The ladder and the clock: cancer pain and public policy at the end of the twentieth century. J Pain Symptom Manage 2005;29:41-54.

4. Wiffen PJ, Edwards JE, Barden J, McQuay HJ. Oral morphine for cancer pain. Cochrane Database Syst Rev 2003;(4):CD003868.

5. Stockler M, Vardy J, Pillai A, Warr D. Acetaminophen (Paracetamol) improves pain and well-being in people with advanced cancer already receiving a strong opioid regimen: a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2004;22:3389-94.

Cochrane Briefs

Systemic Corticosteroids for Acute Exacerbations of COPD

Clinical Question

Do oral or parenteral corticosteroids improve clinical outcomes in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD)?

Evidence-Based Answer

Systemic corticosteroids improve symptoms of acute COPD exacerbations at three days and reduce the likelihood of treatment failure. There is no evidence that they reduce mortality or prevent recurrence at 30 days, but the existing studies may be too small to detect such a benefit. Adverse effects are common but generally are not serious.

Practice Pointers

This Cochrane review updates an earlier meta-analysis with two new studies. Although systemic steroids are widely used for the treatment of acute COPD exacerbations, the authors stress that it is important to know the magnitude of their benefit and the extent of associated side effects. The question of whether oral or intramuscular steroids are more effective was not addressed.

Four of the studies in this analysis involved oral prednisone with an initial dose of 30 to 60 mg tapering over nine to 14 days; in a fifth study, high-dose oral prednisone (2.5 mg per kg) was compared with a moderate dose (0.6 mg per kg). In studies of intravenous methylprednisolone (Solu-Medrol), a variety of dosing regimens were used, from a single 100-mg dose to 72 hours of methylprednisolone followed by a 57-day prednisone taper.

Despite the differences between studies, the review authors were able to combine the results from seven studies of treatment failure and nine studies of mortality. Systemic corticosteroids reduced the likelihood of treatment failure (17 versus 28 percent, P < .0001, number needed to treat = 9), when treatment failure was defined as hospital admission or return to the emergency department. Two studies looked at longer-term treatment failure as measured by hospital admission rates in the 30 days following treatment. Although researchers found no significant difference between steroid and placebo groups (11 versus 15 percent, respectively), these studies were too small for a clinically important difference to be evident, if one existed. There also was no difference in short-term mortality rates, which were approximately 4 percent in both groups (n = 910). Respiratory symptom scores at 72 hours were significantly more likely to be improved if patients received steroids. However, adverse events were common; the number needed to harm was 7 for any adverse event.

In addition to steroids, albuterol (Ventolin) should be used for bronchodilation because of its short onset of action. Ipratropium bromide (Atrovent) may be added. Antibiotics also should be considered for exacerbations that are not clearly triggered by viral infections.1

MARK H. EBELL, M.D., M.S.

Wood-Baker RR, et al. Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005;(1):CD001288.

REFERENCE

1. Institute for Clinical Systems Improvement. Health Care Guidelines. Chronic obstructive pulmonary disease. 4th ed. Bloomington, Minn.: Institute for Clinical Systems Improvement, 2004.

The series coordinator for AFP is Clarissa Kripke, M.D., Department of Family and Community Medicine, University of California, San Francisco.

Copyright © 2005 by the American Academy of Family Physicians. This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

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