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NIH Panel: Treatment of Cancer Pain, Depression, & Fatigue Needs More Attention

Frieden, Joyce

doi: 10.1097/01.COT.0000289195.07247.8f

BETHESDA, MD—Oncologists and primary care physicians need to do a better job of managing cancer patients' symptoms. That is the conclusion of an expert panel convened for a “State-of-the-Science” conference sponsored by the National Institutes of Health.

“Fear of cancer and its consequences must be ameliorated,” said Panel Chair Donald L. Patrick, PhD, MSPH, Director of the Social and Behavioral Sciences Program at the University of Washington in Seattle. “Cancer pain, depression, and fatigue are undertreated, and this is unacceptable.”

One difficulty in discussing management of these three cancer symptoms is that estimates of their frequency are hard to come by.

Estimates of the percentage of cancer patients experiencing pain, for example, run from 14% to 100%. For depression, including major depression as well as depressive symptoms, the range is 1% to 42%; and for fatigue, the estimates are 4% to 91%.

“Such large ranges suggest a lack of uniformity in measurement methodology,” the panel said in its 20-page draft statement. Furthermore, “the systematic literature reviews conducted to address this question found only one study of these symptoms in combination among adults, and none on children.”

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Pain Treatment Beyond the WHO Approach

Among the more controversial issues at the session was how to treat pain. In its draft statement, the 13-member panel cited the well-known three-step analgesic ladder developed by the World Health Organization (WHO).

That approach calls for cancer patients to start out on the lowest level of the ladder—non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen—and then proceed to a combination of NSAIDs and weak opioids like codeine if their pain worsens. The final “rung” on the ladder is strong opioids such as morphine for severe pain.

But Planning Committee member Christine Miaskowski, PhD, RN, FAAN, President of the American Pain Society, who is Professor and Chair of the Physiological Nursing Department at the University of California, San Francisco, said that while the WHO model was a good start, pain management experts have now gone beyond it.

“Patients would come in without much consideration given to the intensity of their pain,” she said, noting that with the WHO model, treatment might not get started fast enough for patients in severe pain.

Figure. C

Figure. C





To replace the WHO model, the National Comprehensive Cancer Network has devised a new treatment algorithm based on a 1-to-10 scale for self-reported pain.

“If a patient's pain is greater than 7, let's treat it as an emergency and get their pain under control,” said Dr. Miaskowski, who was not a panel member but lectured on several topics during the three-day conference. The American Pain Society is now revising the 1994 cancer pain treatment guidelines put out by the Agency for Healthcare Research and Quality to reflect this new line of thinking, she said.

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Depression & Anxiety Common in Cancer Patients

There was more agreement among both panel and audience members regarding the treatment of depression and fatigue.

The treatment of depression in cancer patients appears to vary little from depression treatment for other patients—cancer patients with depression can be helped by psychotherapy as well as by a variety of anti-depressants, the panel noted. But the panel declined to endorse any alternative treatments for depression.

Panel members said that their statement was meant to be more of a summary of the current situation regarding cancer symptom management and a guideline for research priorities, not a treatment guideline.

“This meeting showed that depression and anxiety are really common in patients with cancer,” said panel member Jürgen Unützer, MD, MPH, Associate Professor-in-Residence for the Department of Psychiatry and Biobehavioral Sciences of UCLA School of Medicine.

“Many cancer patients on their own don't seek help from mental health professionals, despite the fact that treatments exist. It's important to support our colleagues in primary care and oncology as they try to manage these symptoms.”

The draft statement emphasized, “Lack of recognition of depression and inadequate resources or skills to treat depression by oncology providers are particularly important. A concern is provider uncertainty about the diagnosis and then the degree and completeness of effect of the anti-depressant medications and psychotherapy in cancer patients.”

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As for fatigue, the panel's first draft statement gave a fairly strong endorsement of the use of erythropoietin alpha, saying that it “is an effective intervention for patients with anemia-related fatigue.”

However, the final draft statement softened that recommendation, noting instead that erythropoietin “can be an effective intervention for treating chemotherapy-related anemia and its related fatigue.”

In a news briefing following the conference, Dr. Patrick noted that several studies have shown a decrease in self-reported fatigue among cancer patients who were being treated with erythropoietin for anemia. The drug is currently approved only for anemia treatment.

There is also some evidence that exercise can help ameliorate fatigue in women with breast cancer, but “this intervention has not been otherwise adequately studied,” the statement said.

Panel members said that their statement was meant to be more of a summary of the current situation regarding cancer symptom management and a guideline for research priorities, not a treatment guideline.

For example, the statement shows “how little data analysis [has been done] in assessing and treating these symptoms for children,” said panel member Bernard Levin, MD, Vice President for Cancer Prevention at the University of Texas M. D. Anderson Cancer Center. “This is calling attention to new areas of research.”

Dr. Patrick added that the conference also made him realize how great the need is for new cancer treatments.

The treatments “should be mechanistically based and grounded in the biology and psychology of the treatment experience,” he said. “From the pharmacological side, [the treatments developed] are often market-driven and not necessarily driven by patient needs.”

A final statement from the panel was expected to be ready by the end of last month, after panel members had time to consider the comments received from the public during the meeting, said a spokeswoman for NIH's Office of Medical Applications of Research.

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Conclusions & Directions for Research

Among the panel's conclusions were the following:



  • Too many cancer patients with pain, depression, and fatigue receive inadequate treatment for their symptoms.
  • Clinicians should use brief assessment tools routinely to ask patients about these symptoms and to initiate evidence-based treatments.
  • Fear of cancer and its consequences must be ameliorated. All patients with cancer should have optimal symptom control from diagnosis throughout the course of illness, irrespective of personal and cultural characteristics.
  • Current evidence to support the concept of cancer symptom clusters is insufficient, and theoretically driven research is warranted.
  • Research is needed on the definition, occurrence, assessment, and treatment of these symptoms alone and together through adequately funded prospective studies.
  • Research is needed into the system barriers to effective symptom control, such as (1) regulatory issues surrounding the prescribing of opioids; (2) adequacy of insurance coverage and reimbursement for pharmacologic and nonpharmacologic symptom management in different care settings; and (3) opportunities for training in symptom management for all health care providers.
  • The state of the science in cancer symptom management should be reassessed periodically.
  • Source(including artwork): NIH State-of-the-Science Conference Statement on Symptom Management in Cancer: Pain, Depression and Fatigue, 7/02
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State-of-the-Science Statements: How They Are Created

The July conference on symptom management was part of the NIH's consensus development program of review statements prepared by a “nonadvocate, non-federal” panel of experts. The program was established in 1977 as a mechanism to judge, in an unbiased, impartial way, controversial topics in medicine and public health.

The review process for writing the documents involves three steps:

  • Presentations by investigators working in areas relevant to the consensus questions during a two-day public session.
  • Questions and statements from conference attendees during open discussion periods that are part of the public session.
  • Closed deliberations by the panel during the remainder of the second day and morning of the third.

The resulting statements (formerly called technology-assessment statements) are independent reports of the panel and are not policy statement of the NIH or the federal government, organizers emphasize.

“The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a ‘snapshot in time’ of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research.”

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Evidence Report

Among the evidence considered by the panel was a comprehensive “evidence report” from the New England Medical Center Evidence-Based Practice Center under contract to the Agency for Healthcare Research and Quality (AHRQ). A summary of the report is available at, as well as from the AHRQ Publications Clearinghouse at 800-358-9295. The full report was expected to be completed by the end of the summer.

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Statement Online

The full state-of-the-science statement is available online at (and then click on the Conference title).

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NLM Bibliography

A bibliography from the National Library of Medicine on managing pain, depression, and fatigue in cancer is available at as a link under Related Conference Materials). A total of 1,803 citations are included, from January 1990 through June 2002, plus selected earlier listings.

© 2002 Lippincott Williams & Wilkins, Inc.
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