CA
NEWS VIEWS
Men who walked regularly ex- As use of nontraditional
perienced less fatigue during cancer therapies surges, so
prostate radiotherapy than do worries and research.
men who didn’t exercise.
& News Briefs
EXERCISE MAY HELP BEAT FATIGUE FROM
PROSTATE RADIATION
Men randomized to a moderate inten-
sity exercise intervention during their
course of radiotherapy for localized pros-
tate cancer reported less fatigue than men
in the control arm of a study recently
published in Cancer (2004;101:550 –557).
Though fatigue is a commonly recog-
nized consequence of radiotherapy, there
is little evidence regarding the best way to
prevent or minimize this side effect. Cli-
nicians often advise patients to continue
their usual activities when possible and rest
if they become tired. Although exercise
interventions have been reported to im-
prove fatigue in patients receiving radio-
therapy or chemotherapy, this strategy had
not been studied in any randomized con-
trolled clinical trials. For this reason, Phyl-
lis M. Windsor, MSc, MD, and colleagues
from Ninewells Hospital and Medical
School in Dundee, Scotland, studied 66
men receiving external beam radiation for
early stage prostate cancer. Half were as-
signed to walk for about 30 minutes several
days a week, while the rest were told to go
about their normal activities, but rest if they
felt tired. Fatigue was measured with the
Volume 54 Y Number 6 Y November/December 2004
New pain medication informa-
tion helps define sound and
suspicious prescription practice
for doctors and law enforcers.
Brief Fatigue Inventory, a nine-item ques-
tionnaire that was self-administered before
beginning radiation, after receiving 5, 10, 15
and 20 fractions of conformal radiotherapy,
and four weeks after the end of treatment.
Before starting radiation, there were no
differences between the two groups in
levels of fatigue. After completing the 20-
fraction course of radiation, men in the
control group reported feeling more tired
than before treatment (p⫽0.013), while
those who were assigned to walking reg-
ularly reported no change in their fatigue
level. Four weeks after the end of treatment,
fatigue scores in the control group had not
yet returned to their pretreatment values,
although the difference was not quite statis-
tically significant (p⫽0.053), whereas the
scores of men who were exercising showed
a slight (albeit nonsignificant) improvement
over their pretreatment reports. A standard-
ized measure of physical performance, the
“shuttle test,” found that the walkers were
able to walk 24% farther (p⫽0.0025) during
the specified interval of time than the con-
trol group at the end of their radiotherapy
regimen.
Those findings aren’t surprising, said
Anna Schwartz, FNP, PhD, FAAN, an
285
News & Views
expert in physical activity during cancer treat-
ment who was not involved with the research.
Radiation tends to cause fatigue that gets worse
over time as the effects of treatment accumu-
late. Exercising can help counteract that trend,
she said.
“Almost all patients feel better if they get up
and move around a little bit,” said Schwartz,
who is Research Associate Professor in Biobe-
havioral Nursing and Health Systems at the
University of Washington in Seattle. “People
who exercise stay stronger, fitter, and actually
get faster and stronger during treatment. So
they are more physically fit and don’t experi-
ence the physical decline and debilitation that
most patients suffer through.”
Windsor and her colleagues, in fact, specu-
lated that men who did not exercise during
treatment may have actually lost muscular con-
ditioning, making everyday activities more dif-
ficult and causing greater fatigue. Encouraging
men with prostate cancer to exercise may not
only help them cope with the fatigue of radi-
ation, they say, but also could have long-term
health benefits.
Schwartz agreed. “It should be the advice
that all cancer patients receive,” she said, pre-
dicting that the prescription will one day be-
come as routine as physical rehabilitation for
cardiac patients.
Exercise may be particularly helpful to men
receiving hormone therapy for prostate cancer,
she added, because it can help counteract the
muscle loss and bone thinning hormone ther-
apy can cause. Walking is a good choice be-
cause it is good for the heart and the bones and
helps patients maintain mobility.
Even small amounts of exercise can help,
Schwartz said. Someone who is unable to walk
for 10 minutes straight can try walking five
minutes in the morning and five in the
evening. Even walking around the living room
is a start. Bedridden patients can ask a physical
therapist or other professional for exercises to
286 CA A Cancer Journal for Clinicians
do in bed that can help them retain some
muscle tone.
The important thing is to do something,
Schwartz said, even when fatigue sets in. Ex-
ercise not only reduces fatigue, but appears to
have an indirect impact on other quality of life
domains. Prior studies have reported that fa-
tigue is correlated with other self-reported side
effects of radiotherapy (for example, urinary
and bowel symptoms in men with prostate
cancer) and with depression.
“Patients tell me all the time the most im-
portant time for them to exercise is when they
feel their worst,” Schwartz said, “but it’s a
balancing act. If someone feels worse when
they exercise, they should rest. But if you keep
saying I’m too tired to exercise today, and
tomorrow, over time you start to get the de-
bilitating effects of not using your body.”
GROWING INTEREST IN COMPLEMENTARY AND
ALTERNATIVE CANCER THERAPIES
Try the Google search “cancer, alternative
OR complementary ” (in other words, cancer
and either complementary or alternative), and
the Internet search engine returns a list of more
than 3.4 million sites with information both
credible and questionable about nontraditional
treatments for cancer.
This abundance of information reflects the
enormous public interest in complementary
and alternative methods (CAM) for cancer
treatment. Despite this volume of Web site
content, clinicians have sparse evidence upon
which to base recommendations for or against
many of these therapies.
“I would guess that over 80% of cancer
patients use... some form of complementary or
alternative therapies,” says Barrie Cassileth,
PhD, Chief of the Integrative Medicine Center
at Memorial Sloan-Kettering Cancer Center in
New York. “Patients often can’t distinguish
which are good and which are harmful, and
we’ve got to help them do that.”

To that end, experts from around the country
have collaborated to form the Society for Inte-
grative Oncology (http://www.integrativeonc.
org). This new professional group is a joint
effort of three major cancer centers with strong
CAM programs—Memorial Sloan-Kettering,
MD Anderson Cancer Center in Houston, and
Boston’s Dana-Faber Cancer Institute—as well as
other cancer-related organizations, including the
American Cancer Society. The new group holds
its first conference November 17–19, 2004, in
New York.
Its goal, said Cassileth, who is the society’s
president, is to promote high-level research of
CAM and get reliable information to doctors so
they can guide their patients.
For instance, some complementary thera-
pies—those which patients use in conjunction
with conventional cancer treatment modali-
ties— can be very helpful, Cassileth said.
Doctors also need to know which therapies
are bogus and potentially dangerous—treat-
ments typically considered “alternative” be-
cause patients may use them instead of
traditional treatments. An article earlier this
year in CA: A Cancer Journal for Clinicians
(2004;54:110 –118) reviewed the evidence for
nearly a dozen alternative cancer therapies and
found that they don’t hold up under scrutiny.
Such therapies should no longer be considered
“unproven,” wrote author Andrew Vickers,
PhD, of Memorial Sloan-Kettering. Rather, “it is
time to assert that many alternative therapies have
been ‘disproven,’” he said.
Then there are treatments that fall some-
where in between the “proven” and the “dis-
proven”— herbs, for instance.
“Botanicals have tremendous potential,”
Cassileth said, “but... at this point, patients only
have access to what’s available over the counter
in the form of supplements, but those... should
be avoided 关during treatment兴 because of their
potential to interact negatively with traditional
therapy.”
CA Cancer J Clin 2004;54:285–291
Research is being conducted, she said, but
the process is slow.
Despite the unknowns, herbal supplements
are popular among cancer patients. As many as
63% use these remedies, according to some
studies.
A study of women being treated for breast
and gynecologic cancers at MD Anderson
found that 48% used some type of herbal or
vitamin supplement (Journal of Clinical Oncology
2004;22:671– 677). Yet only 53% of these
women told their doctor about it.
Said co-author Judith Smith, PharmD,
BCOP, “We kind of knew that patients
weren’t telling physicians about CAM use;
most of them don’t even consider it medica-
tion.”
Indeed, less than a third of the women in the
study said they thought of herbal products and
vitamins as medication. Botanicals aren’t nec-
essarily benign, though.
An article by National Cancer Institute re-
searchers in the Journal of Clinical Oncology
(2004;22:2489 –2503) reviews evidence on
pharmacokinetic interactions between com-
mon herbal products and drugs used in cancer
therapy.
The review focused on the top-selling
herbal preparations in the US. Among these,
garlic, gingko, echinacea, ginseng, St. John’s
wort, valerian, evening primrose, kava, and
grape seed raised concern regarding docu-
mented or potential interactions with the
membrane transporters responsible for drug ab-
sorption and elimination, and the enzymes that
metabolize many anticancer drugs.
Much of this research has been performed
with in vitro systems or laboratory animals, lead
author Alex Sparreboom, PhD, emphasized;
clinical evidence is scarce.
Nevertheless, patients and doctors should
use caution, experts say, and keep the lines of
communication open.
“I think the best thing to do is to be aware
that patients are likely taking 关herbal supple-
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News & Views
ments兴 and be aware they might not tell you
about it,” said William Figg, PharmD, coau-
thor of the herbal review.
Doctors should question cancer patients
about CAM use and monitor them for unusual
symptoms or reactions that might be caused by
the CAM, he said. Sparreboom suggested doc-
tors keep a list of potentially troublesome com-
pounds, such as those noted in his review, to
ask patients about.
Smith agreed that doctors need to take an
active role in talking to patients about CAM. In
her study, most of the women who didn’t talk
to their doctor about CAM use said it was
because the doctor never asked about it.
NEW GUIDANCE ISSUED FOR OPIOID
PAIN MEDICATION
A set of frequently asked questions and an-
swers created by pain management groups and
the Drug Enforcement Administration (DEA)
could help doctors and patients make better
decisions about use of opioids. The document
outlines steps physicians should take to be sure
they are prescribing these medications lawfully,
and gives suggestions for patients to use when
discussing pain relief with their health care
team.
The document will be distributed to law
enforcement personnel as well as physicians
who are registered to prescribe opioids, and is
also available online at http://www.stoppain.
org/faq.pdf.
The goal, developers said, is to help physi-
cians and law enforcers strike a balance be-
tween providing effective pain relief to people
who need it without contributing to the grow-
ing problems of prescription drug diversion and
abuse.
“We have two serious societal problems—
the undertreatment of pain, and drug abuse and
diversion—that are intertwined through pre-
scription pain medications. We address both
problems in this document, and hope it will
288 CA A Cancer Journal for Clinicians
bring some clarity to the issue,” said Russell
Portenoy, MD, chairman of the Department of
Pain Medicine and Palliative Care at Beth Israel
Medical Center in New York, and lead pain
expert on the project.
Studies suggest that more than 40% of pa-
tients with cancer aren’t getting enough pain
relief, Portenoy said. In part, the problem stems
from concerns about becoming addicted to
opioid drugs; some patients and doctors are
simply afraid to try them.
More recently, though, burgeoning pre-
scription drug abuse and high-profile prosecu-
tions of doctors prescribing opioids illegally
have had a chilling effect on the medical com-
munity, said David Joranson, MSSW, another
member of the group that developed the new
guidelines.
“We already knew that for years physicians
have been concerned about being investigated
if they prescribed controlled substances,” said
Joranson, who is Director of the Pain and Pol-
icy Studies Group at the University of Wiscon-
sin Comprehensive Cancer Center. “But now
we hear that patients can’t find a physician who
will prescribe opioids.”
Some pharmacies, he added, won’t even
stock these medications because they fear being
robbed by drug dealers or addicts.
The new guidelines should help address that
situation by providing “some clarifications
about what does or does not constitute ques-
tionable activity in the eyes of the DEA,” said
Patricia Good of the DEA’s Office of Diversion
Control. It also helps law enforcement officers
understand what is considered sound medical
practice, she said.
The endorsement of the DEA is “truly sig-
nificant” said Mary Simmonds, MD, a medical
oncologist and immediate past president of the
American Cancer Society. She was not in-
volved in developing the guidelines.
If doctors feel more confident prescribing
opioids, patients are more likely to get the relief
they need, she said.

In addition to describing the steps doctors
should take when assessing pain and determin-
ing whether opioids are appropriate, the new
document gives doctors some advice on spot-
ting a person who is likely to abuse or divert
drugs. It also clarifies the differences between
true drug addiction, and drug tolerance or
physical dependence.
The distinction is important, said Joranson,
because fear of addiction keeps so many people
from getting proper pain relief. People who use
opioids may well become physically dependent
over time—if they quit the drugs abruptly, they
will experience withdrawal symptoms. Or they
may develop a tolerance to the drug, requiring
higher doses to achieve pain relief. But those
conditions aren’t the same as addiction.
“Addiction is a much more complex disease
that occurs in vulnerable people due to genet-
ics, biology, environment,” he said. “It in-
volves maladaptive behaviors and a compulsive
need to continue using 关these drugs兴 for non-
medical purposes.”
The World Health Organization and major
national and international scientific organiza-
tions have recognized the difference between
addiction and physical dependence, Joranson
said. Yet misperceptions persist.
“Every clinical panel has always said the risk
of addiction is so low in patients with cancer
that it really shouldn’t be a consideration, yet
people continue to be concerned and the rea-
son for that is they don’t understand addic-
tion,” he said.
Simmonds agreed. “People think if they be-
come tolerant they will eventually become ad-
dicted, or that there won’t be a sufficient dose
to relieve their pain,” she said, “and that’s not
true.
“All these myths are in everybody’s mind
and they’re fearful of taking medication. But
for moderate to severe pain, a nonopioid is not
going to be potent enough and there’s no need
to suffer.”
CA Cancer J Clin 2004;54:285–291
Cancer pain is complex, Simmonds said. It
can involve multiple types of pain in the same
person for different reasons, and may even be
combined with pain from other conditions. A
patient may need to try different dosages or
different medications, or combine medications
to achieve relief.
The document encourages patients to talk
openly with their physician about their level of
pain, and to seek out a doctor who takes these
concerns seriously. Patients should tell the doc-
tor if the medication isn’t working or if it
causes problematic side effects.
People seeking pain relief must also under-
stand that doctors have certain procedures they
need to follow in order to stay within the law.
“Doctors act in ways that patients may see as
capricious or idiosyncratic,” Portenoy said,
“when really it’s that the doctor needs to be
sure he’s acting with the right documentation
and within the parameters of the law.”
MRI FINDS BREAST CANCER IN HIGH-RISK WOMEN
Magnetic resonance imaging (MRI) can de-
tect breast cancers mammograms miss in
women at increased risk, according to Dutch
researchers. Their finding, published in the
New England Journal of Medicine (2004;351:427–
437), lends support to the notion that screening
with both methods may be a better option for
high-risk women than using either one alone.
“These new investigations expand our
knowledge in a very important area, which is
how to screen for breast cancer in very high-
risk groups,” said Robert Smith, PhD, Director
of Cancer Screening for the American Cancer
Society. “At this point in time, the amount of
information we have is quite thin with respect
to age to begin screening and the best way to
screen in women who are at higher risk.”
Annual screening with mammography is al-
ready recommended by the American Cancer
Society and other organizations for women
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News & Views
aged 40 and older at average risk of getting
breast cancer. But for women at high risk—
those with a strong family history of the disease
or with a genetic mutation that predisposes
them to breast cancer—that schedule may not
be enough.
These women are at greater risk of devel-
oping breast cancer before age 40, when reg-
ular screening would ordinarily begin; or they
may have cancers that grow very fast, develop-
ing in between mammograms. Moreover,
mammograms are less effective in younger
women because their breast tissue is denser,
making the images harder to read. And in some
cases, the types of tumors high-risk women
develop are less identifiable by mammography.
ACS guidelines advise high-risk women to
discuss with their doctor other screening meth-
ods—like MRI or ultrasound—that can be
used to supplement regular mammography.
Beginning screening at a younger age or
screening more frequently are also options.
Mieke Kriege, MSc, of the Rotterdam Fam-
ily Cancer Clinic at Erasmus Medical Center,
and colleagues from a number of Dutch cen-
ters, recruited 1,909 women at increased risk
for breast cancer because of a family history of
the disease and/or a genetic mutation. The
women were given a physical breast exam by a
doctor every six months, and a mammogram
and MRI scan every year.
Fifty breast carcinomas were found within a
median follow-up period of 2.9 years. For 45 of
these, sufficient data were available for com-
parison of mammography and MRI. MRI
found 32 tumors, of which 22 were not visible
on the corresponding mammogram. Overall,
mammography detected 18 tumors, of which
eight were not visible with MRI. Mammo-
grams were better able to find cases of ductal
carcinoma in situ (DCIS); five of six DCIS
lesions were identified by mammogram. MRI
found only one of six DCIS cases, but it was
the one missed by mammography.
290 CA A Cancer Journal for Clinicians
The tumors found in women who partici-
pated in this study were significantly smaller
and less likely to have spread to axillary lymph
nodes than those found in two age-matched
control groups of women with breast cancer.
“Our study shows that the screening pro-
gram we used, especially MRI screening, can
detect breast cancer at an early stage in women
at risk for breast cancer,” wrote Kriege and
colleagues.
They do not suggest, however, that MRI is
an appropriate screening tool for women at
average risk of developing cancer.
For one thing, the cost of MRI is about
$1,000 to $1,500, compared to $100 to $150
for a mammogram. And MRI has a higher rate
of false-positive results than mammography,
leading to costs, discomfort, and anxiety asso-
ciated with unnecessary follow-up procedures.
“In our study, screening by MRI led to
twice as many unneeded additional examina-
tions as mammography (420 versus 207) and
three times as many unneeded biopsies (24
versus 7),” the researchers wrote.
Those drawbacks make MRI impractical for
use on women who aren’t especially likely to
develop breast cancer. For women at high risk,
though, the trade off is more balanced.
“The fact that the rate of false-positives is
higher 关with MRI兴 is of very little consequence
to women at high risk,” said Smith. “Everyone
would like to avoid a false positive, but the
greater priority is to detect breast cancer early.”
Although the findings are not definitive
enough to make explicit recommendations that
high-risk women begin screening at a particu-
lar age and with a particular method or com-
bination of methods, Smith said, the study
lends support to the ACS guideline for high-
risk women to consider supplementing regular
mammography with MRI.
“The current thinking is that mammogra-
phy plus MRI offers greater advantages to
younger, very high-risk women than either

modality alone,” he said. “The more we learn
about which tumors MRI detects and which it
does not detect, and how we account for fail-
ures in both modalities to detect breast cancer
early, the greater the potential for establishing
tailored 关screening兴 regimens for high-risk
groups that will be more effective.”
Improving screening in this group of
women could have important long-term im-
plications, Smith noted. Many women who
know they are at very high risk of developing
breast cancer choose bilateral prophylactic mas-
CA Cancer J Clin 2004;54:285–291
tectomy and/or oophorectomy to reduce the
chances they will get cancer. Better screening
could allow some women to choose more in-
tensive surveillance, or postpone the decision
about prophylactic surgery to a later time.
“The more we learn about early detection 关in
this group of women兴, the more we may gain
confidence that more intensive, regular screening
is a viable and perhaps even competing option to
other, more difficult and nonreversible decisions
such as prophylactic surgery,” he said.
© American Cancer Society, Inc., 2004.
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