The influence of such factors should also be examined during studies
aimed at defining the efficacy of specific treatments and their
associated side effects. Drug interactions during long-term cancer pain
treatment require clarification. It is unclear whether a mechanism-
based approach to diagnosing and relieving each component of pain
in an individual is more effective than an empiric regimen in which
each patient's treatment is based upon pain intensity alone. Another
key unanswered question is how to optimally combine drug with non-
drug therapies, given that the latter are safe and inexpensive. Despite
the importance of pediatric cancer pain control, practically no
analgesic drug trials focus on children.
High-quality trials of cancer pain relief should enroll greater numbers
of patients for longer intervals than has generally been true in the past;
apply blinding and active placebos when appropriate, or uniform
control treatments otherwise; employ adequate between-arm washout
intervals and consider advancing disease state in crossover trials; and
assess side effects, pain mechanisms, and rest, incident, or
breakthrough pain in a standardized, combinable fashion.
Investigations of cancer pain and its control should seek to evaluate
the influence of gender, race, age, psychosocial context, ethnicity, and
culture on the experience and report of pain.
Prevalence of Cancer-related Fatigue
Estimations of fatigue prevalence have been performed in the setting
of many types of cancer treatment, in the palliative setting, and among
cancer survivors, but the data is by no means consistent or
comprehensive. Many types of cancer were not specifically
addressed.
Study Selection
Only studies that assessed the prevalence of the symptom as the
primary purpose of the study were used for estimating the prevalence
of cancer-related symptoms. For assessment, both retrospective and
prospective studies were used, as well as randomized and
nonrandomized trials, and cross-sectional and longitudinal studies.
Randomized controlled trials were used to analyze efficacy of
interventions.
Prevalence of cancer-related pain.
Prevalence of cancer-related depression.
Prevalence of cancer-related fatigue.
Assessment of cancer-related pain.
Assessment of cancer-related depression.
Assessment of cancer-related fatigue.
Treatment of cancer-related pain.
Treatment of cancer-related depression.
Treatment of cancer-related fatigue.
For some of these topics, in particular the treatment of cancer pain,
there are multiple questions. The Evidence-Based Practice Center
(EPC) produced the evidence report on the Management of Cancer
Pain based on a literature search conducted in December 1998. For
the cancer-related pain topics, the results for the key questions
addressed in the prior EPC report have been thoroughly updated. At
the request of the conference planning committee, two new topics
were added to the treatment of cancer-related pain: oral mucositis
and post-herpetic neuralgia. The methodological approach is
summarized and the new evidence reported. Readers are referred to
the earlier evidence report for detailed information about the
methodological approach and the findings. New systematic reviews
are also included for the symptoms of cancer-related depression and
cancer-related fatigue.
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Return to Contents
Availability of the Full Report
The full evidence report from which this summary was taken was
prepared for the Agency for Healthcare Research and Quality
(AHRQ) by the New England Medical Center Evidence-based
Practice Center (EPC), Boston, MA, under contract number
290-97-0019. Printed copies may be obtained free of charge from
the AHRQ Publications Clearinghouse by calling 1-800-358-9295.
Requesters should ask for Evidence Report/Technology Assessment
No. 61, Management of Cancer Symptoms: Pain, Depression, and
Fatigue.
The Evidence Report is also online at the National Library of
Medicine Bookshelf, or can be downloaded as a set of PDF files or
as a zipped file.
Although trazodone, an atypical antidepressant, showed some benefit
in treating depressive symptoms, it is not commonly used as an
antidepressant because of severe sedation at therapeutic doses.
Although there have been reports describing alternative or
complementary therapy programs, there have been no controlled trials
for their efficacy for depression in people with cancer.
Other tools applied in the selected studies include global evaluations
of efficacy and the McGill-Melzack pain questionnaire. Also applied
were measures of analgesic consumption and a four-point side effect
scale. Descriptions of the need for detailed assessment conducted
within a psychosocial framework are presented in virtually all
guidelines or monographs on cancer pain management. A voluminous
literature describes the multidimensional, experiential nature of cancer
pain and links poor control of cancer pain to impaired quality of life,
including functionality.
Prevalence of Cancer-related Depression
Major depression and depressive symptoms occur frequently in
patients with cancer. Despite standardized measures to calculate
incidence and prevalence, there is a wide range of reported data.
Prevalence rates varied from 10 to 25 percent for major depressive
disorders and a similar range exists for clinically significant depressive
symptoms. This range is the probable result of several factors that
include timing of the assessment, concurrent treatment, medical
morbidity, and pain, gender, and age. Cancer patients are a
heterogeneous population with different sociodemographics, cancer
types, treatments, and responses to treatment. Given that the
estimated point prevalence of major depression in the general
population is 2.2 percent, the rates in cancer patients may be at least
four times greater.
This disturbing finding reflects data from developed countries, where
patients are often in tertiary care or specialist consultative settings.
The likelihood of pain increases, as does its severity, with advancing
cancer stage. (Minorities, women, and the elderly may be at greater
risk for undertreatment of cancer pain.) Pain is generally not
eliminated, despite analgesic therapy administered according to the
World Health
Study Selection
Only studies that assessed the prevalence of the symptom as the
primary purpose of the study were used for estimating the prevalence
of cancer-related symptoms. For assessment, both retrospective and
prospective studies were used, as well as randomized and
nonrandomized trials, and cross-sectional and longitudinal studies.
Randomized controlled trials were used to analyze efficacy of
interventions.
The searches were supplemented with reviews of bibliography of
selected references. The EPC also identified published meta-analyses
and used their data for selected topics.
Overview
This evidence report on Management of Cancer Symptoms: Pain,
Depression, and Fatigue was produced on request from the Office of
Medical Applications of Research (OMAR) at the National Institutes
of Health (NIH) for a State-of-the-Science Conference.
" The First Amendment requires that restrictions on commercial
speech must directly advance a substantial government interest and be
no more extensive than necessary to serve that interest. Commissioner
Swindle explained that "[b]ecause it has not been proven that the false
superior efficacy belief in this case is likely to linger, there is no false
belief that needs to be corrected to prevent deception; therefore,
corrective advertising cannot directly advance any substantial
governmental interest."
The Order requires ads and packaging for Doan's pills to include,
clearly and conspicuously, the message, "Although Doan's is an
effective pain reliever, there is no evidence that Doan's is more
effective than other pain relievers for back pain." The statement will
be carried on all packaging and advertising for one year, except radio
and television ads of 15 seconds or less, and until Novartis has
expended on Doan's advertising an amount equal to the average spent
annually during the eight-year campaign - $8 million.
In March 1998, Administrative Law Judge (ALJ) Lewis F. Parker
upheld the FTC charges that the Doan's ads were unsubstantiated and
false but did not impose a corrective ad remedy sought by complaint
counsel. Both parties appealed the ALJ's decision to the full
Commission.
Availability of the Full Report
The full evidence report from which this summary was taken was
prepared for the Agency for Healthcare Research and Quality
(AHRQ) by the New England Medical Center Evidence-based
Practice Center (EPC), Boston, MA, under contract number
290-97-0019. Printed copies may be obtained free of charge from
the AHRQ Publications Clearinghouse by calling 1-800-358-9295.
Requesters should ask for Evidence Report/Technology Assessment
No. 61, Management of Cancer Symptoms: Pain, Depression, and
Fatigue
The Evidence Report is also online at the National Library of
Medicine Bookshelf, or can be downloaded as a set of PDF files or
as a zipped file.
Data that address individual variations in preferences for, responses
to, and costs incurred by these options are a foundation for potential
evidence-based approaches to cancer pain control, but are sparse.
For example, the spinal route of analgesia is widely employed but
much remains to be learned about optimal patient selection, the
comparative efficacy of spinal drug infusion versus systemic drug
administration, and the selection of initial or secondary agents or
combinations. Exploring these fundamental questions will enhance the
ability of translational clinical research to clarify the clinical relevance
of an increasing number of basic insights into unique mechanisms and
mediators of cancer pain.
One randomized controlled trial evaluated oral transmucosal fentanyl
citrate for breakthrough pain (using a study design in which rescue
doses of morphine were available) and demonstrated its superiority to
placebo. Another randomized study in ambulatory cancer patients
provided evidence for greater analgesia and faster onset of relief after
oral transmucosal fentanyl citrate than after the usual rescue drugs
used by these patients. The EPC found no randomized controlled
trials addressing analgesic efficacy and safety of NSAIDs selective for
the cyclooxygenase-2 isozyme in treating cancer pain. The use of
bisphosphonates and radiation therapy are both supported by the
retrieved trials. Unfortunately, studies that point to the optimal
sequence of application of the many currently available interventions
for pain control were not identified.
Assessment of Cancer-related Pain
Many types of instruments are applied to assess pain and related
analgesic outcomes. In 218 trials, 125 distinct tools were employed.
By far the most frequently employed were unidimensional scales of
pain intensity, followed by scales of pain relief, then measures of peak
or summed pain intensity differences between experimental and
control groups. Other tools applied in the selected studies include
global evaluations of efficacy and the McGill-Melzack pain
questionnaire. Also applied were measures of analgesic consumption
and a four-point side effect scale. Descriptions of the need for
detailed assessment conducted within a psychosocial framework are
presented in virtually all guidelines or monographs on cancer pain
management. A voluminous literature describes the multidimensional,
experiential nature of cancer pain and links poor control of cancer
pain to impaired quality of life, including functionality. Current
expectations for detailed, multidimensional assessment of cancer pain,
including quality of life assessment, during cancer care contrast with
the minimalist assessments of pain intensity presented during relatively
brief observation intervals reported in nearly all of the trials. Side
effects limit analgesic dosage and hence impede pain control in many
patients, yet only one of the 16 most widely employed outcomes
measures is concerned with side effects; that one is a coarse, four-
point measure.
Prevalence of cancer-related pain.
Prevalence of cancer-related depression.
Prevalence of cancer-related fatigue.
Assessment of cancer-related pain.
Assessment of cancer-related depression.
Assessment of cancer-related fatigue.
Treatment of cancer-related pain.
Treatment of cancer-related depression.
Treatment of cancer-related fatigue.
For some of these topics, in particular the treatment of cancer pain,
there are multiple questions. The Evidence-Based Practice Center
(EPC) produced the evidence report on the Management of Cancer
Pain based on a literature search conducted in December 1998. For
the cancer-related pain topics, the results for the key questions
addressed in the prior EPC report have been thoroughly updated. At
the request of the conference planning committee, two new topics
were added to the treatment of cancer-related pain: oral mucositis
and post-herpetic neuralgia. The methodological approach is
summarized and the new evidence reported. Readers are referred to
the earlier evidence report for detailed information about the
methodological approach and the findings. New systematic reviews
are also included for the symptoms of cancer-related depression and
cancer-related fatigue.
Reporting the Evidence
The State-of-the-Science Conference planning committee
acknowledged that many symptoms are relevant to the care of cancer
patients, but because the current conference can address only a
limited number of topics, pain, depression, and fatigue were selected
as the focus. The planning committee identified prevalence,
assessment, and treatment as the key issues to be addressed for each
of the three chosen symptoms. The following questions were
formulated by the conference planning committee:
