Vol. 19, No.

2 March/April 2004
Association of Community Cancer Centers
A SUPPLEMENT TO
Oncology Economics & Program Management
2 An Overview for Clinicians
by Faith D. Ottery
5 New Approaches in Reversing Cancer-related
Weight Loss
by Vickie E. Baracos
11 Multimodality Approaches to Optimize
Survivorship Outcomes: Body Composition,
Exercise, and Nutrition
by Faith D. Ottery, Suzanne R. Kasenic, and
Regina S. Cunningham
Sponsored by Savient Pharmaceuticals, Inc.
©
Copyright 2004. Association of Community Cancer Centers. All rights reserved. No
part of this publication may be reproduced or transmitted in any form or by any means
without written permission. Articles and other contributed materials represent the opin-
ions of the authors and do not represent the opinions of the Association of Community
Cancer Centers or the institution with which the author is affiliated unless the contrary
is specified. Cover Image/Photodisc.com
Issues in
Nutrition
and Cancer:
UPDATE 2004
…an increasing number of cancer survivors are living with
long-term effects of disease and treatment that impair their
functioning and quality of life. While diagnosis, treatment,
and even cure-oriented research continues, it is imperative
that there be a parallel commitment to the improvement
of the status of everyday living for cancer survivors.
Development of research-based clinical interventions in
these areas holds promise for significant improvement in
functioning and quality of life for cancer survivors and
may constitute valuable rehabilitation techniques that
can be adjunctive to standard therapies.
1
—Maryl Winningham, RN, PhD
hen I was asked to coordinate this
supplement to address the inclusion
of the principles and practice of nutri-
tional oncology into an integrated
approach to cancer care, I was partic-
ularly honored since the supplement
is to be published on the celebration
of the 30th anniversary of the Association of Community
Cancer Centers (ACCC). Dr. Winningham’s comments
echo components of ACCC’s Mission: to preserve and
protect the entire continuum of quality cancer care.
2
Standardization of assessment and evidence-based
clinical interventions are imperative to optimize patient
functionality and quality of life across the cancer experi-
ence. In the following articles, we applied a framework,
defined by Courneya and colleagues,
3
for physical exercise
across the cancer experience to the broader concepts of
functionality and quality of life (Figure 1). Known as the
“Framework PEACE” (Physical Exercise Across the
Cancer Experience), this proposed framework divides the
cancer experience into six time periods: two prediagnosis
(prescreening and screening/diagnosis), and four postdiag-
nosis (pretreatment, treatment, posttreatment, and
resumption).
3
As with the original concept, it is hoped that
this framework will stimulate a more comprehensive and
in-depth inquiry into the role of functionality and quality
of life in cancer control.
QUALITY OF SURVIVORSHIP AND NUTRITION
With the successes in cancer diagnosis and treatment
accomplished over the past 70-plus years, we have a
growing population of cancer survivors. Quality of sur-
vivorship is important, whether we are talking about the
four postdiagnosis periods for a given survivor or the two
prediagnosis periods for the family members who want
and need to address aspects of lifestyle as they affect risks
for developing cancer, as well as the prognosis of that
cancer should it develop.
For many people, quality of survivorship is as
important as the duration of survivorship, whether one is
addressing acute (e.g., having enough energy to go out and
get the morning paper), intermediate (e.g., getting back to
work or usual activity) or chronic time frames (e.g., chron-
ic sequelae of body composition loss and fatigue years
after completion of therapy as in lymphoma
4
or lung can-
cer
5
). In addition, it can be postulated that those patients
who maintain better nutritional status and body composi-
tion during and after primary therapy are better and more
willing candidates for therapy should the cancer recur.
PREVENTION, PHYSICAL ACTIVITY, AND
HEALTH
Cancer is a disease process that affects not only the indi-
vidual patient but also his or her family members and sig-
nificant others. Often when a parent is diagnosed with a
cancer, the question is asked, “What can we do so that my
daughter/son doesn’t have to go through this?” Any
answer to questions about what one can do to prevent
cancer or improve prognosis must include a discussion
about the components of nutrition and physical activity,
with the goal of optimizing body composition and metab-
olism. While we do not specifically address the issues of
nutrition and exercise in cancer prevention in any of the
following articles, the discussion of this quality of sur-
vivorship would be incomplete without a brief summary
of what is known about nutrition, exercise, and body
composition in terms of cancer risk and prognosis.
The proposed Health Determinants and Health
Outcomes Set of the Healthy People 2010
6
program
includes eight indicators representative of health determi-
nants: physical environment, poverty, high school gradua-
tion, tobacco use, weight, physical activity, health insur-
ance, and cancer detection. These indicators have been
chosen because they represent some of the most powerful
determinants of health for which meaningful action can be
taken at multiple jurisdictional levels, ranging from the
national and state levels to individuals and families in
neighborhoods and communities.
Two indicators address health outcomes. The first
focuses on prevention of mortality associated with inten-
tional and unintentional injuries, while the second address-
es the extent to which illness, injury, or disability prevents
people from performing important social roles. The
2 Issuis ix Nuriiriox axo Caxcii: Uioari :cc¡ March/April 2004
Issues in Nutrition and Cancer:
An Overview for Clinicians
by Faith D. Ottery, MD, PhD
W
indicator set, therefore, recognizes that just as society has
an effect on health, so too the health of the population has
an effect on the functioning and productivity of society.
Since the 1940s body weight, body fat distribution,
and adult weight gain have been linked to the development
of endometrial, postmenopausal breast, colon, esophageal,
and renal carcinoma incidence and breast carcinoma prog-
nosis.
7-9
Studies also point to a possible role for physical
activity in cancer incidence, because of the interrelation-
ship between weight and physical activity. Considerable
data indicate a 40 to 50 percent reduction in colon carcino-
ma incidence in active compared to sedentary individuals
and a 30 to 40 percent reduction in breast carcinoma inci-
dence among women engaging in three or more hours per
week of regular vigorous activity. Somewhat more limited
and less consistent data associate prostate and lung
carcinoma with inactivity.
7, 10,11
In the context of the growing interest in “metabolic
syndrome” or hyperinsulinemia as a determinant of com-
promised health in terms of obesity, type II diabetes melli-
tus, and cardiovascular risk, data now suggest a role for
this syndrome in risk for breast, colorectal, and prostate
cancer and for their prognosis.
12-18
Current evidence sug-
gests that obesity, lack of physical activity, alcohol con-
sumption, and a typical high-energy Western diet are all
associated with the development of insulin resistance and
hyperinsulinemia and may stimulate the growth of
tumors, particularly breast and colorectal tumors.
12,14-16,19
Hyperinsulinemia has also been associated with mortality
in breast cancer patients.
20
Elevated waist-to-hip ratio,
representing a higher abdominal fat distribution, is a mark-
er of insulin resistance and hyperinsulinemia
22,23
and has
been associated with both incidence of and mortality
of several chronic diseases, including heart disease,
hypertension, diabetes mellitus, and cancer.
24-26
The articles that compose this supplement address
areas of clinical importance in caring for cancer sur-
vivors—from those undergoing current therapy to those
for whom chemotherapy or radiation are somewhat dis-
tant memories. The topics discussed in the following arti-
cles are part of the “food for thought” as ACCC celebrates
its 30th Anniversary and clearly support the mission state-
ment and the vision that form the foundation of the
Association.
Faith D. Ottery, MD, PhD, is the founding president
of the Society for Nutritional Oncology Adjuvant
Therapy (NOAT) and current chair of the Rehabilitation
Committee of the Multinational Association of Supportive
Care in Cancer (MASCC). Her research focuses on the
complex interplay of nutrition and exercise that forms the
basis of many of the seminal publications in the field of
nutritional oncology. She trained in medical oncology
and was a practicing surgical oncologist at Fox Chase
Cancer Center from 1987-1994. She is director of medical
affairs in oncology, HIV, and geriatrics for Savient
Pharmaceuticals, Inc.
REFERENCES
1
Winningham M. Strategies for managing cancer-related fatigue
syndrome: A rehabilitation approach. Cancer. 2001;92:988-997.
2
Association of Community Cancer Centers. http://www.accc-
cancer.org/about/vision.asp. Accessed January 2004.
3
Courneya KS and Friedenreich CM. Framework PEACE: An
organizational model for examining physical exercise across the
cancer experience. Ann Behav Med. 2001;23:263-272.
4
Oldervoll LM, Kaasa S, Knobel H, Loge JH. Exercise reduces
fatigue in chronic fatigued Hodgkin’s disease survivors – results
from a pilot study. Eur J Cancer. 2003;39:57-63.
5
Langendijk JA, et al. Quality of life after curative radiothera-
py in Stage I non-small-cell lung cancer. Int J Radiat Oncol
Biol Phys. 2002;53(4):847-53.
6
Institute of Medicine. Available at: http://www.nap.edu.html/
healthy3. Accessed January 2004.
I
O
Issuis ix Nuriiriox axo Caxcii: Uioari :cc¡ March/April 2004 3
Cancer
Control
Outcomes
Prevention Detection Buffering Coping
Rehabilitation Health Promotion
Survival
Prescreening Screening Pretreatment Treatment Post-treatment Resumption
Palliation
Prediagnosis Postdiagnosis
Diagnosis
Cancer-related Time Period
➝ ➝ ➝





Figure 1. An organizational
model for examining
Physical Exercise Across
the Cancer Experience
(Framework PEACE)
4 Issuis ix Nuriiriox axo Caxcii: Uioari :cc¡ March/April 2004
7
Scientific Program Committee. Physical activity across the can-
cer continuum: Report of a workshop. Review of existing knowl-
edge and innovative designs for future research. Cancer. 2002;
95:1134-43.
8
Ballard-Barbash R. Energy balance, anthropometrics, and can-
cer. In: Heber D, Blackburn GL, Go VLM, editors. Nutritional
Oncology. San Diego. Academic Press, Inc. 1999:137-153.
9
National Center for Health Statistics, Center for Disease
Control. Cardiovascular fitness In: National Health and
Nutrition Examination Survey. Survey questionnaires, examina-
tion components, and laboratory components. Available at:
http://www.cdc.gov/nchs/data/meccomp.pdf. 39-43. Accessed
January 2004
10
Colditz GA, Cannuscio CC, Frazier AL. Physical activity and
reduced risk of colon cancer: Implications for prevention. Cancer
Causes Control. 1997;8:649-667.
11
McTiernan A, Ulrich CM, Yancey D, et al. The physical
activity for total health (PATH) study: Rationale and design.
Med Sci Sports Exerc. 1999;31(9):1307-12.
12
Borugian MJ, Sheps SB, Kim-Sing C, et al. Waist-to-hip ratio
and breast cancer mortality. Am J Epidemiology. 2003;158:963-
968.
13
Bruning PF, Bonfrer JM, van Noord PA et al. Insulin resistance
and breast-cancer risk. Int J Cancer. 1992;52:511-16.
14
Del Giudice ME, Fantus IG, Ezzat S, et al. Insulin and related
factors in premenopausal breast cancer risk. Breast Cancer Res
Treat. 1998;47:111-20.
15
Borugian MJ, Sheps SB, Whittemore AS, et al. Carbohydrates
and colorectal cancer risk among Chinese in North America.
Cancer Epidemiol Biomarkers Prev. 2002;11:187-93.
16
Giovannucci E. Insulin and colon cancer. Cancer Causes
Control. 1995;6:164-79.
17
Barnard RJ, Aronson WJ, Tymchuk CN, et al. Prostate cancer:
Another aspect of the insulin-resistance syndrome? Obes Rev.
2002;3(4):303-8.
18
Hsing AW, Gao YT, Chua S Jr, et al. Insulin resistance and
prostate cancer risk. J Natl Cancer Inst. 2003;95(1):67-71.
(Comment: J Natl Cancer Inst. 2003;95(14):1086-7; author reply
1087.)
19
Reaven GM. Banting Lecture 1988. Role of insulin resistance in
human disease. Nutrition. 1997;13(1):65;discussion 64, 66.
20
Goodwin PJ, Ennis M, Pritchard KI, et al. Fasting insulin and
outcome in early-stage breast cancer: Results of a prospective
cohort study. J Clin Oncol 2002;20:42-51.
21
Nilsen TI, Vatten LJ. Prospective study of colorectal cancer
risk and physical activity, diabetes, blood glucose, and BMI:
exploring the hyperinsulinemia hypothesis. Br J Cancer.
2001;84;417-422.
22
Stoll BA. Obesity and breast cancer. Int J Obes Relat Metab
Disord. 1996;20:389-92.
23
Hollmann M, Runnebaum B, Gerhard I. Impact of waist-to-
hip ratio and body-mass—index on hormonal and metabolic
parameters in young, obese women. Int J Obes Relat Metab
Disord. 1997;21:476-83.
24
Folsom AR, Kaye SA, Seller TA, et al. Body fat distribution
and 5-year risk of death in older women. JAMA. 1993;269: 483-7.
25
Folsom AR, Kushi LH, Anderson KE, et al. Associations of
general and abdominal obesity with multiple health outcomes in
older women: The Iowa Women’s Health Study. Arch Intern
Med. 2000;160:2117-28.
26
Friedenreich CM, Courneya KS, Bryant HE. Case-control
study of anthropometric measures and breast cancer. Int J
Cancer. 2002;99:445-52.
Issuis ix Nuriiriox axo Caxcii: Uioari :cc¡ March/April 2004 5
ancer cachexia is a profound metabolic
process characterized by the breakdown of
skeletal muscle, as well as abnormalities in
fat and carbohydrate metabolism. The diag-
nosis of cachexia is made by a history of
substantial weight loss in the context of
advanced disease and a physical examination demonstrat-
ing muscle wasting. The prognostic significance of weight
loss in cancer patients is well established, with weight loss
strongly associated with shortened survival and poor
response to therapy from the earliest disease stages
through to advanced cancer. The negative nitrogen balance
underlying cancer cachexia leads to a significant wasting of
skeletal muscle and other lean tissues. This lean tissue loss
reduces patient mobility, jeopardizes respiratory function,
is related to reduced immunity, and is associated with
poor performance status and outcome. Stabilizing muscle
loss or regaining lean tissue mass must, therefore, be
considered primary targets of cachexia therapy.
Research on the biology of skeletal muscle and its
regulatory anabolic and catabolic factors is many decades
old. Skeletal muscle is terminally differentiated. Thus, it is
not cell division and cell death that contribute to muscle
mass, but mainly synthesis and degradation of proteins
within existing cells. These metabolic processes have been
described in considerable biochemical detail and are
known to be precisely controlled.
A host of factors stimulating muscle protein synthesis
and degradation has been characterized. These fall into
three major categories: muscular work/mechanical activi-
ty, endocrine factors, and nutrients. Muscle mass and
function are dependent on this simple triad. In any given
person and within any given physiological state, these
three categories of influences combine to define muscle
mass. A fourth category of stimuli exists: a series of cata-
bolic factors that mainly occur during disease or injury,
including tumor-derived factors.
1
FACTORS INFLUENCING MUSCLE LOSS AND
GAIN
The plasticity of skeletal muscle—its ability to adapt—
covers a broad range.
Muscle mass falls to a minimum when:
s
Contractile work is limited or absent
s
Nutrients (especially amino acids for building muscle
protein and necessary co-factors) are unavailable
s
Anabolic hormones, such as insulin and testosterone,
are at low levels or when muscle is resistant to their
action
s
Catabolic factors related to stress (i.e., cortisol) or
disease (i.e., proinflammatory cytokines) are present.
Muscle mass rises to its maximum when:
s
Contractile work is frequent, especially resistance-type
activity (i.e., weight-lifting)
s
Nutrients (especially amino acids for building muscle
protein and necessary co-factors) are not limiting
s
Anabolic hormones, such as insulin and testosterone,
are at optimal levels and muscle is sensitized to their
action
s
Catabolic factors related to stress (i.e., cortisol) or
disease (i.e., proinflammatory cytokines) are absent.
ANABOLIC COMPETENCE—THE SPORTS
MEDICINE APPROACH
The commonly used approach in sports for building
maximal muscle mass is well known: resistance training
(weight-lifting); nutritional supplements, especially pro-
tein; and a variety of natural and synthetic hormones to
provide the three strong anabolic signals to which muscles
can respond. These signals are synergistic, not just addi-
tive in their action, which can lead to spectacular gains of
muscle in some individuals. While some of the interven-
tions have been controversial, the model does demon-
strate the importance of integrating the approaches.
The approach used in sports training is highly devel-
oped. Detailed progressive weight-training programs,
addressing specific muscle groups are available in any
sports training manual, as well as in physical therapy
texts. The amino acid requirements for maximal muscle
growth are at least partially understood, and these are
commercially available as amino acid and protein supple-
New Approaches in Reversing
Cancer-relatedWeight Loss
by Vickie E. Baracos, PhD
IN BRIEF
Should those of us involved in anticancer therapy
of patients adopt the mindset of our sports medicine
colleagues? The few available trials suggest that in
cancer patients, resistance training, adequate protein,
and amino acid or amino acid derivative supplemen-
tation can each individually promote net gain of lean
body mass and associated function. If these observa-
tions are borne out, it seems possible to conjecture
that a combination therapy involving several or all of
these may hold the promise of much more important
gains—as seen in healthy people.
C
6 Issuis ix Nuriiriox axo Caxcii: Uioari :cc¡ March/April 2004
ments in various combinations and forms. While these
were initially used based on anecdotal evidence, there is
an increased research database supporting the use of some
and refuting others. Elegant work has been done on the
appropriate timing of protein feeding, relative to the
timing and type of exercise bouts.
2
Synthetic anabolic
steroids derived and developed from the basic structure of
testosterone have been intensified in their anabolic action
on skeletal muscle, while minimizing other effects, such as
liver damage and male pattern hair growth.
3,4
Creatine
supplementation in the diet is used as an adjunct in this
recipe, as creatine phosphate serves as an essential phos-
phate donor for the synthesis of ATP, a critical energy
source for initiating muscle activity.
5-17
Evidence of the success of this integrated muscle-
building program can be seen in gymnasiums, bodybuild-
ing competitions, and football fields. The sports model is
simple, and—insofar as it involves diet and activity—can
be generally inexpensive and can be used by patients
directly or coordinated by the clinician. Use of pharmaco-
T
he goal of nutritional intervention in patients
with cancer is to prevent or reverse the progres-
sive weight loss and inanition that is seen in up
to 80 percent of patients at some point in their disease
or treatment. Unfortunately, even this simple goal
is rarely achieved, and there has been little or no
progress in impacting the gold standard of survival by
simply addressing nutritional interventions. Clinicians
who use nutritional therapies alone to combat weight
loss in cancer patients experience three common frus-
trations: 1) lack of consistent reversal of weight loss
with intervention, 2) lack of repletion of lean tissue or
muscle, and 3) lack of translation of any change in
weight or nutritional parameters into improved
oncology outcomes.
This relative lack of success can be presumed to be
because of a one-dimensional approach that does not
integrate nutrition into a program of comprehensive
cancer care. A paradigm of integrated intervention has
been developed that supports anabolism or anabolic
competence, defined as that state which optimally
supports protein synthesis and lean body mass.
1
This
paradigm also addresses the more global problems of
muscle and organ function, immune competence,
functionality, and quality of life. This approach is illus-
trated in Figure 1 and demonstrates the importance of
addressing the three primary components of interven-
tion: nutrition, the hormonal milieu (including both
classic hormones and cytokines), and exercise.
Until recently, treatment of cancer cachexia has
focused on the provision of macro- and micronutrients
to reverse weight loss, with little clinical attention
to the composition of body tissues lost or repleted.
During the past decade, the level of understanding of
the etiology of muscle catabolism in cancer cachexia,
as well as intermediary markers of muscle breakdown
and lipid mobilization, have served to re-focus
research into interventional options for cancer cachex-
ia that target the functional aspects of body composi-
tion (lean tissue)—instead of simply focusing on ener-
gy reserves (adipose tissue). This appreciation is
addressed by Vicki Baracos, PhD. A more comprehen-
sive review of the understanding and management of
cancer cachexia has recently been published by
Baracos and her colleagues in Canada.
2
REFERENCES
1
Langer CJ, Hoffman JP, Ottery FD. Clinical significance of
weight loss in cancer patients: Rationale for the use of ana-
bolic agents in the treatment of cancer-related cachexia.
Nutrition. 2001;17(suppl 1):S1-S20.
2
MacDonald N, Easson AM, Mazurak VC, et al.
Understanding and managing cancer cachexia. J Am Coll
Surg. 2003;197:143-161.
Integrated Interventions in Nutritional Oncology
Nutritional
Milieu
Exercise
Hormonal
Milieu
Optimal
Composition
&
Physiologic
Function
©
Ottery,1997
Figure 1. The Three Primary Components
of Nutritional Intervention
logic intervention, such as anabolic agents, is to be regard-
ed as a medical intervention, with appropriate dosing and
monitoring in the context of the underlying disease.
APPLYING THE SPORTS MEDICINE MODEL TO
PATIENTS WITH WASTING SYNDROMES
Fatigue is the most distressing phenomenon experienced
by cancer patients.
18
Vogelzang and colleagues used a sur-
vey designed to characterize the epidemiology of cancer-
related fatigue from the perspectives of the patient (n =
419, median age 65), primary caregiver (n = 200), and
oncologist (n = 197).
18
The principal cancer diagnoses
were breast in females and genitourinary in males. Cancer
treatment included chemotherapy (59 percent), radiation
therapy (63 percent), or both (24 percent); 20 percent of
patients received their last treatment within 6 weeks, 31
percent within 7 to 52 weeks, and 49 percent more than
one year ago.
More than three-fourths of patients (78 percent)
experienced fatigue, defined as a general feeling of debili-
tating tiredness or loss of energy, during the course of
their disease and treatment, 32 percent daily, and 32 per-
cent reported fatigue significantly affecting their daily
routines. Caregivers reported observing fatigue in 86 per-
cent of the index patients, and oncologists perceived that
76 percent of their patients experienced fatigue. Patients
felt that fatigue adversely affected their daily lives more
than pain (61 percent vs. 19 percent). Most oncologists
(80 percent) believed fatigue is overlooked or undertreat-
ed, and most patients (74 percent) considered fatigue a
symptom to be endured. Fifty percent of patients did not
discuss treatment options with their oncologists, and only
27 percent reported that their oncologists recommended
any treatment for fatigue.
Given this background, it is important to consider
that fatigue is multifactorial in etiology. However, the sig-
nificant catabolic loss of muscle is an important target for
interventional consideration. It is possible to argue that we
already have the knowledge necessary to improve muscle
mass and consequently patient function and mobility—
that is, we know the sports-training approach that results
in increased muscle mass. What seems to be lacking is the
translation of this knowledge into practice. Are the “new”
integrated approaches to supporting anabolism to wasting
syndromes simply the application of well-established con-
cepts? Should those of us involved in anticancer therapy
of patients adopt the mindset of our sports medicine col-
leagues? This integrated approach of nutrition, resistance
and aerobic exercise, and appropriate hormonal support
has already been adopted by researchers in muscle wasting
in the elderly,
19-21
in patients with wasting syndromes
associated with AIDS,
22,23
and chronic obstructive
pulmonary disease.
24-26
Clinical researchers in cancer cachexia and anorexia
can learn from the related research work of their col-
leagues in other disciplines. Some results from clinical
trials looking at reversal of muscle wasting in noncancer
disease may be immediately translatable to cancer popula-
tions. Research in the sports medicine area has led the
way with interventions, including creatine, amino acids,
and anabolic agents, in combination with exercise pro-
grams tailored to develop muscle mass and optimize per-
formance. Clinical research on wasting in the elderly has a
relatively long history and has been the focus of activity
in large research centers. AIDS and COPD cachexia
research has been enhanced by targeted funding and is
also quite active at this time.
RESISTANCE MUSCLE TRAINING TO BUILD
MUSCLE MASS AND STRENGTH
Currently literature on exercise training and muscle
anabolism is very extensive, and a review of this literature
is outside the scope of this article. (See page 11.) However,
exercise training is shown clearly to stimulate muscle pro-
tein synthesis and to develop muscle mass and functional
status. A key point emerging from the research is that our
concept of who can exercise should be revisited. Various
patients considered too frail and ill to exercise have been
shown to benefit from exercise. Schulte and Yarasheski
19
provide a pertinent example in frail elderly (76 to 92 years
of age) who participated in up to three months of
weightlifting. Study participants showed increased
biosynthesis of myosin heavy chain and mixed muscle
proteins, as do younger people. This finding suggests that
the protein synthetic machinery adapts rapidly to
increased contractile activity and that the adaptive
responses are maintained, even in frail elders.
In addition, evidence from recent publications indi-
cates that repeated exercise may enhance the fitness,
strength, and quality of life of cancer patients. The stud-
ies have addressed patients with a variety of different
cancers. In one study, men with prostate cancer who
were scheduled to receive androgen deprivation therapy
were randomly assigned to an intervention group that
participated in a resistance exercise program three times
per week for 12 weeks or to a waiting list control
group.
27
Men in the resistance intervention group
demonstrated fewer fatigue-related problems with
Issuis ix Nuriiriox axo Caxcii: Uioari :cc¡ March/April 2004 7
Clinical researchers in cancer
cachexia and anorexia can learn
from the related research work
of their colleagues in other
disciplines. Some results from
clinical trials looking at reversal
of muscle wasting in noncancer
disease may be immediately
translatable to cancer
populations.
8 Issuis ix Nuriiriox axo Caxcii: Uioari :cc¡ March/April 2004
activities of daily living and had a higher quality of life
and higher levels of upper-body and lower-body muscu-
lar fitness than men in the control group.
Dimeo and coworkers
28
have produced a surprising
series of reports on exercise in patients undergoing
chemotherapy, including high-dose chemotherapy with
stem cell rescue. These patients are generally very sick in
the aftermath of chemotherapy, yet they are able and will-
ing to exercise. These daily physical training programs
reduce the treatment-related loss of physical performance
in patients with hematological malignancies undergoing
chemotherapy. The lack of reported negative effects and
the consistency of the observed benefits lead to the con-
clusion that physical exercise may
provide a low-risk therapy that can
improve patients’ capacity to perform
activities of daily living and improve
their quality of life.
29
BEYOND EXERCISE: AN
INTEGRATED APPROACH
In addition to the exercise interven-
tions that have been studied in
patients with cancer, the use of other
interventions that may be used by
patients needs to be addressed by cli-
nicians caring for patients with can-
cer. Clinicians should question
patients with an open mind regarding any aspect of com-
plementary medicine. If the issue is not raised by the
clinician, the patient or family may fail to include the
information in any medical review.
Creatine. Creatine is a very commonly-used supple-
ment among athletes who believe creatine builds muscle
and increases muscle energy, enabling them to train longer
and perform at a higher level. The sports medicine litera-
ture is replete with trials that demonstrate that healthy
individuals taking creatine achieve a significant increase in
lean body mass in comparison with placebo and may also
improve muscle function.
5-17
Increase in muscle mass may
be secondary to the athlete’s ability to maintain a program
of physical activity, although it remains possible that crea-
tine may have a direct effect on muscle protein synthesis.
A creatine trial including normally active older men
(59 to 72 years of age) used a double-blind, placebo-con-
trolled design with repeated measures and showed
improved muscle performance with seven days of admin-
istration trial.
20
These data indicate that seven days of
creatine supplementation was effective at increasing sever-
al indices of muscle performance, including functional
tests in older men without adverse side effects. Creatine
supplementation may be a useful therapeutic strategy for
older adults to attenuate loss in muscle strength and
performance of functional living tasks.
If the sports medicine data on creatine are applicable
without intense exercise programs, perhaps creatine may
also be used adjunctively to rebuild the muscles of cancer
patients. Currently, evidence on this straightforward
proposition is not available, as there are few crossover
studies from sports medicine to wasting disorders and
additional research is clearly needed. Creatine is regarded
as a safe supplement for healthy people and is available
over the counter in health food stores, as only minor
adverse effects have been reported. Mild abnormalities in
renal function may occur.
12
Creatine has not been tested
in cancer patients, and if considered, should be used with
with caution in individuals with renal impairment or with
fragile electrolyte balance.
Anabolic Agents. Testosterone was identified and
characterized more than 70 years ago and recognized
shortly thereafter as a hormone that stimulated muscle
growth. Many clinical studies report that testosterone and
its analogs support muscle growth,
30-36
yet anabolic
steroids have only achieved a tentative hold in medical
practice aside from their use in clearly demonstrated
hypogonadal states. Physicians have been slow to act on
the possible applications of anabolic steroids in patients
with catabolic losses of muscle mass. In part, this lack of
use stems from the tainted association with illicit use of
these compounds, as well as lack of clinical studies until
the past decade. In addition, the long-term effects of
androgens, which may include virilizing in women, liver
damage in both sexes, and adverse changes in serum
lipids, have discouraged their use. More recent studies
with attenuated androgens, also known as anabolic agents,
have limited some of these concerns. In view of the pro-
found suffering associated with wasting and chronic ill-
ness, and in view of the very substantial improvements in
the efficacy and side-effect profile of these compounds, a
re-evaluation of the role of anabolic steroids in these
conditions is currently underway.
Testosterone levels are commonly reduced in patients
with severe illness. For example, a hypogonadal state is
often present in patients with advanced lung cancer.
31,35
Testosterone replacement is simply accomplished, but the
androgen status of cancer patients has been assessed only
on a few highly selected patients. Studies on healthy males
indicate that supraphysiologic injections of testosterone
or its analogs induce muscle synthesis with short-term
use. Testosterone replacement in elderly men, men under-
going knee replacement, and AIDS patients is associated
with improved muscle size and function.
33,37,38
A few studies of testosterone or anabolic agents in
treatment of weight loss and inanition in patients with
cancer have been carried out. A recently reported trial of
oxandrolone (an oral synthetic derivative of testos-
terone) concluded that weight-losing cancer patients on
this agent not only gained weight, but their weight gain
was also associated with improvement in lean body
mass, improved ECOG performance status, and quality
of life scores, including the functional component.
34,39,40
If the sports medicine data on creatine are
applicable without intense exercise programs,
perhaps creatine may also be used adjunctively
to rebuild the muscles of cancer patients.
This work is particularly interesting because it also
demonstrated that men showed greater gains in lean
body mass. Preliminary data demonstrated that when
patients were stratified into those who lost weight,
stayed weight stable, and gained weight during oxan-
drolone treatment, the most responsive group of men
gained up to 13.9 pounds over a four-month period and
the majority of this (10.9 pounds) was lean body mass.
39
This result—net gain of lean body mass—is in striking
contrast to the often-expressed belief that cancer cachex-
ia is inevitable and that its progression is unstoppable.
A subsequent placebo-controlled study of oxan-
drolone confirmed the results of the open label study
referenced above, with significant increases in weight
and lean tissue weight at month two of a four-month
study.
34,40
These studies extend some of the earlier results
noted with the injectable anabolic androgenic steroid,
nandrolone.
41-43
These data address the potential effec-
tiveness and safety of anabolic agents in cancer-related
weight loss.
41-44
While many believe it is not possible to
maintain weight in patients with advanced malignancy,
others have established that important gains of weight
and lean tissue are possible.
In addition, in view of the evidence of hypogonadism
in patients with advanced cancer, it may be possible to ask
if there is any reason not to offer testosterone replacement
to patients with clinical evidence of androgen deficiency,
if the patient so desires.
Amino Acids. While anabolic therapy directed at the
lean tissues seems unlikely to be entirely successful with-
out provision of the amino acids required for protein
anabolism, this area of research is relatively neglected.
Only a small number of studies look at amino acid supple-
mentation in cancer patients, and the specific amino acids
supplemented are suggested by a relatively sparse literature
on amino acid utilization in tumor-bearing animals.
Supplemental oral N-acetyl-cysteine was reported to
improve quality of life and increase plasma albumin levels
and body cell mass in patients with various forms of inop-
erable cancer, suggesting that cysteine becomes a condi-
tionally dietary essential amino acid in cancer.
45
The lack
of a difference in survival between treated and control
groups indirectly suggests that supplemental cysteine did
not enhance tumor growth.
An amino acid mixture containing glutamine, argi-
nine, and β-hydroxy β-methyl butyrate (a metabolite of
leucine) promoted deposition of lean body mass in non-
small cell lung cancer patients without any reported side-
effects.
46
This proprietary product originated as a sports
supplement and is currently being assessed in a number
of larger, ongoing randomized trials. To formulate amino
acid mixtures optimized to support anabolism and func-
tion in cancer patients, formal assessments of amino acid
requirements using current methods are much needed.
CONCLUSION
The few available trials suggest that in cancer patients,
resistance training, adequate protein, and amino acid or
amino acid derivative supplementation can each individu-
ally promote net gain of lean body mass and associated
function. If these observations are borne out, it seems
possible to conjecture that a combination therapy involv-
ing several or all of these may hold the promise of much
more important gains—as seen in healthy people. In the
age of high technology and super-drugs, this potential
solution to cancer-associated wasting may simply be too
obvious or not sufficiently glamorous to have merited
attention. On the other hand, if it were possible that these
effectors were additive or even synergistic in their actions
on muscle of cancer patients, then 10 or 20 pounds of tis-
sue gain may be realizable in the context of a multimodal-
ity strategy for promoting anabolism in individuals with
cachexia.
This approach, which stems from basic muscle
physiology, does not necessarily address the question of
tumor-derived catabolic factors. Recent work of Tisdale
and colleagues suggest that tumors secrete novel lipolysis-
inducing factors as well as potent catabolic factors specific
for skeletal muscle.
1
The nature and mechanisms of action
of these factors are beginning to be elucidated, and these
will form the basis of targeted therapies, including aspects
that may have an anticatabolic effect.
Vickie E. Baracos, PhD, is professor of protein metabo-
lism in the Department of Nutrition Science and
Oncology at the University of Alberta in Alberta,
Canada.
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Volek JS. Strength nutrition. Curr Sports Med Rep. 2003;2:189-93.
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12
Juhn MS, Tarnopolsky M. Potential side effects of oral creatine
supplementation: A critical review. Clin J Sport Med.
1998;8(4):298-304.
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Kreider RB. Effects of creatine supplementation on perform-
ance and training adaptations. Mol Cell Biochem. 2003;244:89-94.
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van Loon LJ, Oosterlaar AM, Hartgens F, et al. Effects of cre-
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atine loading and prolonged creatine supplementation on body
composition, fuel selection, sprint and endurance performance
in humans. Clin Sci (Lond). 2003;104:153-62.
15
Rawson ES, Volek JS. Effects of creatine supplementation and
resistance training on muscle strength and weightlifting per-
formance. J Strength Cond Res. 2003;17:822-31.
16
Branch JD. Effect of creatine supplementation on body com-
position and performance: A meta-analysis. Int J Sport Nutr
Exerc Metab. 2003;13:198-226.
17
Chwalbinska-Moneta J. Effect of creatine supplementation on
aerobic performance and anaerobic capacity in elite rowers in
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18
Vogelzang NJ, Breitbart W, Cella D, et al. Patient, caregiver,
and oncologist perceptions of cancer-related fatigue: Results of
a tripart assessment survey. The Fatigue Coalition. Semin
Hematol. 1997;34(3 suppl 2):4-12.
19
Schulte JN, Yarasheski KE. Effects of resistance training on
the rate of muscle protein synthesis in frail elderly people. Int J
Sport Nutr Exerc Metab. 2001;11(suppl):S111-8.
20
Gotshalk LA, Volek JS, Staron RS, et al. Creatine supplemen-
tation improves muscular performance in older men. Med Sci
Sports Exerc. 2002;34:537-543.
21
Lambert CP, Sullivan DH, Freeling SA, et al. Effects of testos-
terone replacement and/or resistance exercise on the composi-
tion of megestrol acetate stimulated weight gain in elderly men:
A randomized controlled trial. J Clin Endocrinol Metab.
2002;87:2100-2106.
22
Fairfield WP, Treat M, Rosenthal DI, et al. Effects of testos-
terone and exercise on muscle leanness in eugonadal men with
AIDS wasting. J Appl Physiol. 2001; 90:2166-2171.
23
Strawford A, Barbieri T, Van Loan M, et al. Resistance exercise
and supraphysiologic androgen therapy in eugonadal men with
HIV-related weight loss: A randomized controlled trial. JAMA.
1999;281:1282-90.
24
Creutzberg EC, Wouters EF, Mostert R, et al. A role for ana-
bolic steroids in the rehabilitation of patients with COPD? A
double-blind, placebo-controlled, randomized trial. Chest.
2003;124(5):1733-42.
25
Jagoe RT, Engelen MP. Muscle wasting and changes in muscle
protein metabolism in chronic obstructive pulmonary disease.
Eur Respir J. (suppl.) 2003;46:52s-63s.
26
Debigare R, Marquis K, Cote CH, et al. Catabolic/anabolic
balance and muscle wasting in patients with COPD. Chest.
2003;124(1):83-9.
27
Segal RJ, Reid RD, Courneya KS, et al. Resistance exercise in
men receiving androgen deprivation therapy for prostate cancer.
J Clin Oncol. 2003;21:1653-9.
28
Dimeo F, Schwartz S, Fietz T, et al. Effects of endurance train-
ing on the physical performance of patients with hematological
malignancies during chemotherapy. Support Care Cancer.
2003;11:623-8
29
Ardies CM. Exercise, cachexia, and cancer therapy: A molecu-
lar rationale. Nutr Cancer. 2002;42:143-57.
30
Basaria S, Wahlstrom JT, Dobs AS. Clinical review 138:
Anabolic-androgenic steroid therapy in the treatment of chronic
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31
Simons JP, Schols AM, Buurman WA, et al. Weight loss and
low body cell mass in males with lung cancer: Relationship with
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(Lond). 1999; 97:215-223.
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Langer CJ, Hoffman JP, Ottery FD. Clinical significance of
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2001;17(suppl 1):S1-20.
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Ferrando AA, Sheffield-Moore M, Yeckel CW, et al.
Testosterone administration to older men improves muscle func-
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34
Von Roenn JH, Tchekmedyian S, Ottery F. Oxandrolone
increases weight, lean tissue, performance status and quality of
life (QOL) scores in cancer-related weight loss (Poster 114).
14th International Symposium: Supportive Care In Cancer at
the combined meeting of The Multinational Association of
Supportive Care in Cancer and The International Society of
Oral Oncology. Boston, MA, June 23-26, 2002.
35
Tchekmedyian S, Thropay J, Von Roenn J, Ottery F. Patients
with aerodigestive tract cancer and pre-exiting weight loss:
Performance status, quality of life, and laboratory parameters
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American Society of Therapeutic Radiology and Oncology.
New Orleans, LA, October 6-10, 2002.
36
Sheffield-Moore M, Urban RJ, Wolf SE, et al. Short-term oxan-
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young men. J Clin Endocrinol Metab. 1999;84:2705-2711.
37
Amory JK, Chansky HA, Chansky KL, et al. Preoperative
supraphysiological testosterone in older men undergoing knee
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Bhasin S, Storer TW, Javanbakht M, et al. Testosterone replace-
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Tchekmedyian S, Fesen M, Price LM, et al. On-going placebo-
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Von Roenn JH, Tchekmedyian S, Cleary S, et al. State of the
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Darnton SJ, Zgainski B, Grenier I, et al. The use of an anabolic
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Von Roenn JH, Tchekmedyian S, Hoffman R, et al. Safety of
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Hack V, Breitkreutz R, Kinscherf R, et al. The redox state as a
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Am J Surg. 2002;183:471-9.
Issuis ix Nuriiriox axo Caxcii: Uioari :cc¡ March/April 2004 11
nce, in giving a nutritional presentation to
the National Surgical Adjuvant Breast and
Bowel Project, I made the comment that
the initials NSABP actually referred to
the phrase “Nutritional Stability Always
Brings Pleasure.”
In other words, significant changes—increases or
decreases—in a patient’s weight or body composition are
undesirable for anyone going through cancer treatment.
This perspective allows a consistent and integrated philo-
sophic approach to cancer care, whether one is addressing
a postmenopausal woman with breast cancer who is at risk
for significant weight gain and potential adverse oncologic
outcomes or the patients with cancers in which progressive
weight loss and cachexia may be the rule, also associated
with adverse outcomes.
The cornerstone for addressing appropriate body
composition and metabolic balance in patients with cancer
is a multimodality approach that combines nutrition,
physical activity (aerobic and resistance exercises), and
pharmacologic intervention as necessary. This integrated
approach is important from time of diagnosis through
treatment and in long-term survival.
PHYSICAL ACTIVITY AND SURVIVORSHIP
“Life is a metabolic dance between anabolic and catabolic
processes.”
1
Optimal cancer rehabilitation techniques
should focus both on the reduction of unnecessary cata-
bolic processes (such as unnecessary activity restrictions or
anemia) as well as building on anabolic processes to opti-
mize daily functioning and quality of survivorship (QOS).
Family members and clinicians frequently advise peo-
ple with cancer to rest and to reduce the amount and
intensity of their activities—both during and after treat-
ment.
1
Interestingly, these recommendations may exacer-
bate the fatigue that plagues the survivor. In fact, living
alone may actually contribute to improved functionality as
well as supporting continued independence. Physical inac-
tivity can contribute to disuse muscle atrophy, contribut-
ing to loss of cardiorespiratory fitness and to fatigue.
Catabolic losses of weight that occur as the result of
cytokine-mediated changes in metabolism or chronic use
of corticosteroids can also contribute significantly to loss
of muscle mass during cancer treatment. The combined
losses of weight and lean tissue may be synergistic and if
not reversed with cancer rehabilitation may progress
further over time due to impaired physical activity.
Structure and function of muscle and bone are
dependent on physical activity combined with appropriate
nutrition and hormonal milieu supporting anabolism. In
healthy volunteers, complete bed rest for as short as a
week has been associated with a 1-4 percent loss of muscle
mass and a number of metabolic changes including insulin
resistance and increase in extremity fat.
2-4
These changes
can be exacerbated in the setting of fever, corticosteroids,
and the proinflammatory cytokines associated with malig-
nancy. Each of these settings is also associated with mobi-
lization of bone calcium, again with implications for the
long-term survivor.
Accelerated loss of bone mineral density, with its
ensuing complications of pain and risk for compression
and other pathological or traumatic fractures, becomes
increasingly important with increased survivorship—in
terms of both numbers of survivors and duration of sur-
vivorship. Inactivity, combined with direct complications
of chemotherapy and changes in the survivor’s hormonal
milieu (orchiectomy, contraindications to hormone
replacement therapy or HRT, and corticosteroid use) all
contribute to increased risk of progressive bone deminer-
alization and osteoporosis. Resistance exercise is increas-
ingly recognized as an important therapeutic intervention
for preventing or reversing bone loss and its complica-
tions.
5-11
Studies of physical exercise in cancer initially focused
on aerobic exercise in women with breast cancer.
12
More
recently, resistance exercise has been added to the regimens
with impact on cardiorespiratory fitness, improved body
composition with increased lean tissue and decrease in fat
mass, as well as improved strength and functionality. There
is an increasing body of literature supporting the impor-
tance of physical exercise in cancer survivors with a variety
of different cancer types with demonstrated improvement
in 1) functional capacity, 2) perception and measured
Multimodality Approaches to
Optimize Survivorship Outcomes:
Body Composition, Exercise,
and Nutrition
by Faith D. Ottery, MD, PhD, Suzanne R. Kasenic, RD, and Regina S. Cunningham, PhD, RN, AOCN
®
IN BRIEF
Our perceptions of the effects of deterioration in
nutritional status and body composition must
expand beyond the realm of acute toxicity to one of
long-term and quality survivorship. The cornerstone
for addressing appropriate body composition and
metabolic balance in patients with cancer is a multi-
modality approach that combines nutrition, physical
activity (aerobic and resistance exercises), and phar-
macologic intervention as necessary. This integrated
approach is important from time of diagnosis
through treatment and in long-term survival.
O
12 Issuis ix Nuriiriox axo Caxcii: Uioari :cc¡ March/April 2004
fatigue, 3) lessening requirements for medications for
nausea or pain, 4) psychological or emotional aspects of
improved self-esteem, mood, sense of control, overall
sense of well-being, reduced depression and anxiety, and
5) immunologic function as assessed by increased natural
killer cell activity.
13-19
The specific physical aspects of cancer rehabilitation
can include one or more of the following: deficit-related
physical and occupational therapy; individual or group
exercise programs; institutional, gym, home-based, or
nature-based programs; aerobic (walking, cycling, swim-
ming, dancing), stretching, and resistance exercise (elasti-
cized resistance bands, light-to-moderate weight lifting).
CORTICOSTEROIDS: CHRONIC
MUSCULOSKELETAL SEQUELAE
Corticosteroids have a number of physiologic effects that
contribute to broad use in patients receiving cancer thera-
py as well as in treatment of survivor co-morbidities.
Antiemetic, anti-inflammatory, and antineoplastic roles
are common as well as used in terminal palliative care for
its central effects to improve sense of well-being and
short-term improvements in affect and appetite.
In the context of the current discussion, it is important
to consider the effects of glucocorticosteroids on lean tis-
sue and the skeleton. The development of muscle weak-
ness and atrophy is a well-known complication of therapy
with exogenous glucocorticosteroids, and is probably the
most common form of drug-induced myopathy encoun-
tered in clinical practice.
20-22
The clinical presentation of
steroid-induced muscle weakness is characterized by an
insidious onset and is usually painless. The proximal mus-
cles of the arms and legs are affected first with the lower
extremities demonstrating the earliest signs of weakness.
There is a relative sparing of distal musculature, and
smooth muscle does not appear to be involved. The
patient first notes difficulty climbing stairs and rising from
low chairs because hip girdle and thigh weakness, but by
the time this occurs marked muscle atrophy is evident. In
addition to effects on muscle, glucocorticoids also con-
tribute significantly to bone demineralization and risk
for progressive osteoporosis.
In review of the published literature, exercise is
increasingly included as integral to any intervention
addressing prevention or treatment of musculoskeletal
complications of corticosteroids, regardless of the
underlying disease state utilizing chronic corticosteroids.
Prevention and treatment of corticosteroid-induced
osteoporosis is based upon general measures such as calci-
um and vitamin D supplementation, adequate protein
intake, regular physical exercise, hormonal replacement
therapy and upon specific means like therapies used in
primary osteoporosis. Bisphosphonates, which are potent
bone resorption inhibitors, have been shown to increase
bone mineral density and to decrease fracture rate.
SYNERGY OF NUTRITION AND EXERCISE IN
SURVIVORSHIP
Support of whole-body anabolism is based on an integrated
approach of nutrition, exercise, and support of an appropri-
ate hormonal milieu. Probably the most important aspects
of a synergistic multimodality approach are 1) awareness,
2) assessment, and 3) appropriate intervention.
Lack of awareness regarding the impact of nutrition
and body compositional changes on acute and chronic
aspects of survivorship as well as a lack of awareness of
cost-effective interventional options are the two greatest
impediments to success in addressing acute and chronic
sequelae of cancer therapy. Table 1 addresses the specifics
of this approach. Components as simple as the intake of
adequate protein in chemotherapy toxicity and loss of
muscle mass and function in individuals on bed rest to the
chronic sequelae of malnutrition and body compositional
change have long been underappreciated in the armamen-
tarium of the oncologist and are now beginning to play a
role as we address issues of survivorship.
Since the inception of the Association of Community
Cancer Centers (ACCC) 30 years ago, the Association
has set standards of integrated quality oncology care.
Evolution of standardized assessment, as well as recent
research in multimodality intervention, offer new insight
that is immediately applicable to the oncology team.
Today the role of exercise, specialty nutriceutricals
containing omega-3 fatty acids
23
(ProSure
®
, Resource
Support
®
) or β-hydroxy β-methylbutyrate (HMB) with
glutamine and arginine
24
(Juven
®
), anticatabolic agents
such thalidomide
25
(Thalomide
®
), and now anabolic
agents such as oxandrolone
26-28
(Oxandrin
®
) demonstrate
increases in total weight or slowing of weight loss, increase
in lean tissue weight, all of which are with associated func-
tional and quality of life improvements. A newly launched
NCI-sponsored study addressing an integrated approach
of nutrition, exercise and pharmacologic intervention
(oxandrolone vs. megestrol acetate) characterizes the new
model of multimodality approaches for improving quality
of cancer survivorship.
Faith D. Ottery, MD, PhD, is current chair of the
Rehabilitation Committee of the Multinational Association
of Supportive Care in Cancer and director of medical affairs
in oncology, HIV, and geriatrics for Savient Pharma-
ceuticals, Inc. Suzanne R. Kasenic, RD, is oncology nutri-
tionist at Fox Chase Temple Cancer Center in Philadelphia,
Pa. Regina S. Cunningham, PhD, RN, AOCN
®
is chief
nursing officer and director of Ambulatory Services at the
Cancer Institute of New Jersey in New Brunswick, N.J.
REFERENCES
1
Winningham ML. Strategies for managing cancer-related fatigue
syndrome: A rehabilitation approach. Cancer. 2001;92(4 Suppl):
988-997.
2
Shangraw RE, Stuart CA, Prince MJ, et al. Insulin responsiveness of
protein metabolism in vivo following bedrest in humans. Am J
Physiol. 1988; 255(4 pt 1):E548-58.
3
Stuart CA, Shangraw RE, Prince MJ, et al. Bed-rest-induced insulin
resistance occurs primarily in muscle. Metab. 1988;37(8):802-6.
4
Stuart CA, Shangraw RE, Peters EJ, et al. Effect of dietary protein
on bed-rest-related changes in whole-body-protein synthesis. Am J
Clin Nutr. 1990;52(3):509-14.
5
Braith RW, Magyari PM, Fulton MN, et al. Resistance exercise
training and alendronate reverse glucocorticoid-induced osteoporosis
in heart transplant recipients. J Heart Lung Transplant. 2003;22(10):
1082-90.
6
Fiechtner JJ. Hip fracture prevention. Drug therapies and lifestyle
modifications that can reduce risk. Postgrad Med. 2003;114(3):22-28.
7
Mitchell MJ, Baz MA, Fulton MN, et al. Resistance training
prevents vertebral osteoporosis in lung transplant recipients.
I
O
continued on page 14
Issuis ix Nuriiriox axo Caxcii: Uioari :cc¡ March/April 2004 13
Table 1. Practical Assessments in Prevention and Treatment of
Chronic Sequelae of Cancer Therapy
Variable Assessment Intervention
Nutritional Status
Weight, weight history Scale, PG-SGA*
Nutritional intake Patient history, PG-SGA, Nutritional intervention
protein/calorie counts
s
Define macronutrient goals
Protein 0.7 g/lb of ideal weight (1.5 g/kg)/day
Calories 16-18
+
kcal/lb current weight
s
Micronutrient—multivitamin and vitamin,
mineral as indicated
s
Consideration of commercial nutritional
supplements
s
Consideration of specialty nutriceuticals:
HMB or omega-3
Pharmacologic intervention
s
Antiemetics, analgesics, antidepressants;
orexigenic, anticatabolic/antimetabolic or
anabolic agents; others
Nutrition impact Patient history, PG-SGA Behavioral intervention
symptoms
s
Address taste and smell sensory changes
s
CAM: ginger, ice, behavioral
Pharmacologic intervention
s
Antiemetics, analgesics, antidepressants;
orexigenic, anticatabolic/antimetabolic or
anabolic agents; others
Catabolic/metabolic Vitals, concommitant Pharmacologic intervention
stresses meds, PG-SGA
s
Anticatabolic/antimetabolic or anabolic agents,
others
Physical examination: Focused physical exam, Behavioral intervention
muscle, fat, fluid PG-SGA
s
Mixed modality exercise (aerobic,
resistance/strength)
Pharmacological intervention
s
Orexigenic, anticatabolic/antimetabolic or
anabolic agents; diuretics
Body Composition/Bone Behavioral intervention
Mineral Density
s
Mixed modality exercise (aerobic,
resistance/strength)
Pharmacological intervention
s
Orexigenic, anticatabolic/antimetabolic or
anabolic agents; diuretics; vitamins A and D,
calcium, magnesium; bisphosphonates,
parathyroid hormone, other
Physical examination: PG-SGA,
muscle, fat, fluid anthropometrics
Body composition Bioelectrical impedance analysis (BIA)
assessment Dual energy X-ray absorptiometry (DEXA)
Functionality Behavioral intervention
s
Mixed modality exercise (aerobic, strength-
resistance bands, weight lifting)
continued on page 14
14 Issuis ix Nuriiriox axo Caxcii: Uioari :cc¡ March/April 2004
Transplantation. 2003;76(3):557-62.
8
Winett RA, Carpinelli RN. Potential health-related benefits of
resistance training. Prev Med. 2001;33(5):503-13.
9
NIH Consensus Development Panel on Osteoporosis Prevention,
Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and
therapy. JAMA. 2001;285(6):785-95.
10
Kerr D, Ackland T, Maslen B, et al. Resistance training over 2 years
increases bone mass in calcium-replete postmenopausal women.
J Bone Miner Res. 2001;16(1):175-81.
11
Hurley BF, Roth SM. Strength training in the elderly: Effects on
risk factors for age-related diseases. Sports Med. 2000;30(4):249-68.
12
Winningham ML. Effects of a bicycle ergometry program on func-
tional capacity and feelings of control with breast cancer.
Unpublished doctoral dissertation. The Ohio State University,
Columbus, Ohio. 1983.
13
Courneya KS, Friedenriech CM. Relationship between exercise
during treatment and current quality of life among survivors of
breast cancer. J Psychosoc Oncol. 1997;15:35-57.
14
Nelson JP. Perceived health, self-esteem, health habits, and per-
ceived benefits and barriers to exercise in women who have and who
have not experienced stage I breast cancer. Oncol Nurs Forum.
1991;18:1191-1197.
15
Schwartz AL, Mori M, Gao R, et al. Exercise reduces daily fatigue
in women with breast cancer receiving chemotherapy. Med Sci Sports
Exerc. 2001;33:718-723.
16
Kolden GG, Strauman TJ, Ward A, et al. A pilot study of group
exercise training (GET) for women with primary breast cancer:
Feasibility and health benefits. Psychooncol. 2002;11:447-456.
17
Fairey AS, Courneya KS, Field CJ, et al. Effects of exercise training
on fasting insulin, insulin resistance, insulin-like growth factors, and
insulin-like growth factor binding proteins in postmenopausal breast
cancer survivors: A randomized controlled trial. Cancer Epidemiol
Biomarker Prev. 2003;12:721-727.
18
Dimeo F, Bertz H, Finke J, et al. An aerobic exercise program for
patients with haematological malignancies after bone marrow trans-
plantation. Bone Marrow Transplantation. 1996;18:1157-1160.
19
Na YM, Kim MY, Kim YK, et al. Exercise therapy effect on natural
killer cell cytotoxic activity in stomach cancer patients after curative
surgery. Arch Phys Med Rehab. 2000;81:777-779.
20
Mastaglia FL. Adverse effect of drugs on muscle. Drugs.
1982;24:304-321.
21
Braith RW, Welsch MA, Mills RM, et al. Resistance exercise pre-
vents glucocorticoid-induced myopathy in heart transplant recipi-
ents. Med Sci Sports Exerc. 1998;30:483-489.
22
Horber FF, Hoppeler H, Scheidegger JR, et al. Impact of physical
training on the ultrastructure of midthigh muscle in normal subjects
and in patients treated with glucocorticoids. J Clin Invest.
1987;79:1181-119
23
Fearon KC, Von Meyenfeldt MF, Moses AG, et al. Effect of a
protein and energy dense N-3 fatty acid enriched oral supplement
on loss of weight and lean tissue in cancer cachexia: A randomised
double blind trial. Gut. 2003;52(10):1479-86.
24
May PE, Barber A, D’Olimpio JT, et al. Reversal of cancer-related
wasting using oral supplementation with a combination of beta-
hydroxy-beta-methylbutyrate, arginine, and glutamine. Am J Surg.
2002;183:471-9.
25
Khan ZH, Simpson EJ, Cole AT, et al. Oesophageal cancer and
cachexia: the effect of short-term treatment with thalidomide on
weight loss and lean body mass. Aliment Pharmacol Ther.
2003;17:677-82.
26
Von Roenn JH, Tchekmedyian S, Hoffman R, et al. Safety of
Oxandrolone in Cancer-related Weight Loss (Poster N2 #3013) 39
th
ASCO meeting, Chicago, Ill. May 31-June 3, 2003.
27
Tchekmedyian S, Fesen M, Price LM, et al. On-going placebo-con-
trolled study of oxandrolone in cancer-related weight loss (Abstract
1039, Discussed Poster Presentation). 45
th
ASTRO meeting, Salt
Lake City, Utah. October 19-23, 2003. In: Int J Radiat Oncol Biol
Phys. 2003;57(2 suppl):S283-4.
28
Von Roenn JH, Tchekmedyian S, Cleary S, et al. State of the Art in
Cachexia Therapy: Anabolic Steroids. Oral Presentation. 2
nd
Interna-
tional Cachexia Conference, December 4-6, 2003, Berlin, Germany.
Functionality continued Pharmacological intervention
s
Antiemetics, analgesics, antidepressants; or
exigenic, anticatabolic/antimetabolic or anabolic
agents; diuretics; vitamins A and D, calcium,
magnesium, bisphosphonates, parathyroid
hormone, other
Assessment of activities ECOG/Zubrod, Karnofsky,
of daily living PG-SGA
Assessment of change How fast? How often?
from individual’s norm How long to recover?
Borg scale of perceived
exertion
Endurance 6-minute walk
Strength Rise from chair, other,
handgrip strength
*The Patient-Generated Subjective Global Assessment (PG-SGA) tool and worksheets are for patient or clinician use. They can be
found on ACCC’s web site at www.accc-cancer.org/publications/pgsga.pdf, and www.accc-cancer.org/publications/pgsgaworksheet.pdf.
The PG-SGA addresses the global status of the patient from this integrated perspective—weight loss and weight loss history, nutritional
intake, nutrition impact symptoms, ECOG performance status in patient terms, metabolic/catabolic stresses, and physical examination
focused on body composition. From the standpoint of functionality, ECOG or Karnofsky performance status assessments are impor-
tant prognostic indicators, but greater insight may be obtained in terms of functionality and QOS with questions addressing change in
functioning as it impacts that survivor.
Variable Assessment Intervention

The proposed Health Determinants and Health Outcomes Set of the Healthy People 20106 program includes eight indicators representative of health determinants: physical environment. we applied a framework. posttreatment. In the following articles. and resumption). injury. Winningham’s comments echo components of ACCC’s Mission: to preserve and protect the entire continuum of quality cancer care. exercise.g. Ottery. it is hoped that this framework will stimulate a more comprehensive and in-depth inquiry into the role of functionality and quality of life in cancer control. the discussion of this quality of survivorship would be incomplete without a brief summary of what is known about nutrition.g. ranging from the national and state levels to individuals and families in neighborhoods and communities. and even cure-oriented research continues. defined by Courneya and colleagues. health insurance. getting back to work or usual activity) or chronic time frames (e. high school graduation..Issues in Nutrition and Cancer: An Overview for Clinicians by Faith D. it is imperative that there be a parallel commitment to the improvement of the status of everyday living for cancer survivors. physical activity. we have a growing population of cancer survivors. or disability prevents people from performing important social roles. it can be postulated that those patients who maintain better nutritional status and body composition during and after primary therapy are better and more willing candidates for therapy should the cancer recur. with the goal of optimizing body composition and metabolism. Quality of survivorship is important.3 As with the original concept. Dr. the question is asked. RN. Development of research-based clinical interventions in these areas holds promise for significant improvement in functioning and quality of life for cancer survivors and may constitute valuable rehabilitation techniques that can be adjunctive to standard therapies. while the second addresses the extent to which illness. QUALITY OF SURVIVORSHIP AND NUTRITION With the successes in cancer diagnosis and treatment accomplished over the past 70-plus years. tobacco use. quality of survivorship is as important as the duration of survivorship. as well as the prognosis of that cancer should it develop. These indicators have been chosen because they represent some of the most powerful determinants of health for which meaningful action can be taken at multiple jurisdictional levels. and four postdiagnosis (pretreatment.2 Standardization of assessment and evidence-based clinical interventions are imperative to optimize patient functionality and quality of life across the cancer experience. poverty. PHYSICAL ACTIVITY. intermediate (e. chronic sequelae of body composition loss and fatigue years after completion of therapy as in lymphoma4 or lung cancer5). MD. and body composition in terms of cancer risk and prognosis.. PREVENTION. PhD …an increasing number of cancer survivors are living with long-term effects of disease and treatment that impair their functioning and quality of life. “What can we do so that my daughter/son doesn’t have to go through this?” Any answer to questions about what one can do to prevent cancer or improve prognosis must include a discussion about the components of nutrition and physical activity. weight. Known as the “Framework PEACE” (Physical Exercise Across the Cancer Experience). whether we are talking about the four postdiagnosis periods for a given survivor or the two 2 . Often when a parent is diagnosed with a cancer. While diagnosis. treatment. having enough energy to go out and get the morning paper).3 for physical exercise across the cancer experience to the broader concepts of functionality and quality of life (Figure 1).. In addition. treatment.1 —Maryl Winningham. For many people. The first focuses on prevention of mortality associated with intentional and unintentional injuries. PhD W prediagnosis periods for the family members who want and need to address aspects of lifestyle as they affect risks for developing cancer. whether one is addressing acute (e. and cancer detection. While we do not specifically address the issues of nutrition and exercise in cancer prevention in any of the following articles. Two indicators address health outcomes. I was particularly honored since the supplement is to be published on the celebration of the 30th anniversary of the Association of Community Cancer Centers (ACCC). this proposed framework divides the cancer experience into six time periods: two prediagnosis (prescreening and screening/diagnosis).g. AND HEALTH Cancer is a disease process that affects not only the individual patient but also his or her family members and significant others. The I  N  C: U  March/April 2004 hen I was asked to coordinate this supplement to address the inclusion of the principles and practice of nutritional oncology into an integrated approach to cancer care.

Knobel H.20 Elevated waist-to-hip ratio. esophageal.39:57-63. colon. http://www.23 and has been associated with both incidence of and mortality of several chronic diseases. and adult weight gain have been linked to the development of endometrial. 5Langendijk JA. lack of physical activity. 2002. Available at: http://www.14-16. The topics discussed in the following articles are part of the “food for thought” as ACCC celebrates its 30th Anniversary and clearly support the mission statement and the vision that form the foundation of the Association.org/about/vision. Exercise reduces fatigue in chronic fatigued Hodgkin’s disease survivors – results from a pilot study.asp. 2001. and renal carcinoma incidence and breast carcinoma prognosis. because of the interrelationship between weight and physical activity. 3Courneya KS and Friedenreich CM. 2003. and prostate cancer and for their prognosis. Inc.Figure 1.12-18 Current evidence suggests that obesity. Her research focuses on the complex interplay of nutrition and exercise that forms the basis of many of the seminal publications in the field of nutritional oncology. 2Association of Community Cancer Centers. Ann Behav Med. Accessed January 2004. Considerable data indicate a 40 to 50 percent reduction in colon carcinoma incidence in active compared to sedentary individuals and a 30 to 40 percent reduction in breast carcinoma incidence among women engaging in three or more hours per week of regular vigorous activity. type II diabetes mellitus. particularly breast and colorectal tumors.23:263-272.53(4):847-53. including heart disease. data now suggest a role for this syndrome in risk for breast. Quality of life after curative radiotherapy in Stage I non-small-cell lung cancer. and cancer.12. and cardiovascular risk. Int J Radiat Oncol Biol Phys. so too the health of the population has an effect on the functioning and productivity of society. PhD. Somewhat more limited and less consistent data associate prostate and lung carcinoma with inactivity. Ottery. Framework PEACE: An organizational model for examining physical exercise across the cancer experience. Kaasa S. ➝ Cancer Control Outcomes Prevention ➝ Detection ➝ Buffering ➝ Coping ➝ ➝ Survival 3 .19 Hyperinsulinemia has also been associated with mortality in breast cancer patients. Strategies for managing cancer-related fatigue syndrome: A rehabilitation approach. alcohol consumption.7-9 Studies also point to a possible role for physical activity in cancer incidence. MD.html/ healthy3.nap.edu. therefore.accccancer. 4Oldervoll LM. colorectal. is a marker of insulin resistance and hyperinsulinemia22. She is director of medical affairs in oncology. et al. is the founding president of the Society for Nutritional Oncology Adjuvant Therapy (NOAT) and current chair of the Rehabilitation Committee of the Multinational Association of Supportive Care in Cancer (MASCC).7. OI Faith D. representing a higher abdominal fat distribution. Since the 1940s body weight. 2001. 6Institute of Medicine. 10. recognizes that just as society has an effect on health.24-26 The articles that compose this supplement address areas of clinical importance in caring for cancer surI  N  C: U  March/April 2004 vivors—from those undergoing current therapy to those for whom chemotherapy or radiation are somewhat distant memories. postmenopausal breast. She trained in medical oncology and was a practicing surgical oncologist at Fox Chase Cancer Center from 1987-1994.11 In the context of the growing interest in “metabolic syndrome” or hyperinsulinemia as a determinant of compromised health in terms of obesity. Accessed January 2004. HIV. Loge JH. REFERENCES 1Winningham M. Cancer. hypertension. An organizational model for examining Physical Exercise Across the Cancer Experience (Framework PEACE) Diagnosis Rehabilitation ➝ Health Promotion ➝ Palliation Prescreening Screening Pretreatment Treatment Post-treatment Resumption Prediagnosis Postdiagnosis Cancer-related Time Period indicator set. diabetes mellitus. body fat distribution.92:988-997. Eur J Cancer. and a typical high-energy Western diet are all associated with the development of insulin resistance and hyperinsulinemia and may stimulate the growth of tumors. and geriatrics for Savient Pharmaceuticals.

Associations of general and abdominal obesity with multiple health outcomes in older women: The Iowa Women’s Health Study. et al. Center for Disease Control. 11McTiernan A. 13Bruning PF. et al. 21Nilsen TI. Int J Obes Relat Metab Disord. Breast Cancer Res Treat. Ezzat S. and BMI: exploring the hyperinsulinemia hypothesis. et al.52:511-16. Academic Press. Fantus IG. author reply 1087. Bonfrer JM. Insulin resistance and prostate cancer risk. 66.269: 483-7. Banting Lecture 1988. In: Heber D. Cancer. Pritchard KI. et al. Review of existing knowledge and innovative designs for future research. Sheps SB. et al. Another aspect of the insulin-resistance syndrome? Obes Rev. Carbohydrates and colorectal cancer risk among Chinese in North America. Role of insulin resistance in human disease. Kim-Sing C. 2002. and cancer. Physical activity across the can- 17Barnard RJ. J Clin Oncol 2002. San Diego. Cardiovascular fitness In: National Health and Nutrition Examination Survey. Arch Intern Med.47:111-20. Blackburn GL. 1999. 1996. 22Stoll BA. 24Folsom AR. Prospective study of colorectal cancer risk and physical activity. 1997. Physical activity and reduced risk of colon cancer: Implications for prevention. Energy balance. Waist-to-hip ratio and breast cancer mortality.pdf. 2003. 4 I  N  C: U  March/April 2004 . 2000.11:187-93. 2001.99:445-52. 1993. Kaye SA. et al. Impact of waist-tohip ratio and body-mass—index on hormonal and metabolic parameters in young. Cancer Causes Control. et al. Ulrich CM. Cancer Epidemiol Biomarkers Prev. Chua S Jr. 1998.gov/nchs/data/meccomp. Aronson WJ. Tymchuk CN. JAMA. 14Del Giudice ME. Insulin resistance and breast-cancer risk. 95:1134-43. 1995. 39-43.158:963968.20:389-92. van Noord PA et al. Accessed January 2004 10Colditz GA.21:476-83. Body fat distribution and 5-year risk of death in older women. Nutrition. Anderson KE. Ennis M.31(9):1307-12. and laboratory components. Nutritional Oncology.8:649-667. Available at: http://www. 23Hollmann M. Med Sci Sports Exerc. Gerhard I. 9National Center for Health Statistics. Prostate cancer: cer continuum: Report of a workshop. 2002. Br J Cancer. 20Goodwin PJ. Inc. 26Friedenreich CM. 1997. Courneya KS. examination components. anthropometrics. Int J Cancer. et al. Fasting insulin and outcome in early-stage breast cancer: Results of a prospective cohort study. 8Ballard-Barbash R. blood glucose. 15Borugian MJ. Vatten LJ.3(4):303-8.) 19Reaven GM. 18Hsing AW.6:164-79.95(1):67-71. diabetes. Insulin and related factors in premenopausal breast cancer risk. 2002.discussion 64. 25Folsom AR. 12Borugian MJ.13(1):65. Kushi LH. 1999:137-153. obese women. et al. Bryant HE.417-422. (Comment: J Natl Cancer Inst. Go VLM. Yancey D. Survey questionnaires. Whittemore AS. 16Giovannucci E. 2003. Int J Cancer. Gao YT. editors.20:42-51. 1997. Am J Epidemiology. The physical activity for total health (PATH) study: Rationale and design.7Scientific Program Committee. Int J Obes Relat Metab Disord. Frazier AL. Sheps SB.160:2117-28.95(14):1086-7. Cannuscio CC. Case-control study of anthropometric measures and breast cancer. 2003. Cancer Causes Control. Seller TA. Runnebaum B. Obesity and breast cancer. 1992.84. 2002. Insulin and colon cancer. J Natl Cancer Inst.cdc.

Thus. weight-lifting) Nutrients (especially amino acids for building muscle protein and necessary co-factors) are not limiting Anabolic hormones. These metabolic processes have been described in considerable biochemical detail and are known to be precisely controlled.e... Muscle mass and function are dependent on this simple triad. Detailed progressive weight-training programs.e. The prognostic significance of weight loss in cancer patients is well established. This lean tissue loss reduces patient mobility.e.e. These signals are synergistic. as well as in physical therapy texts. s s s C ancer cachexia is a profound metabolic process characterized by the breakdown of skeletal muscle. and amino acid or amino acid derivative supplementation can each individually promote net gain of lean body mass and associated function. cortisol) or disease (i. The amino acid requirements for maximal muscle growth are at least partially understood. the model does demonstrate the importance of integrating the approaches. as well as abnormalities in fat and carbohydrate metabolism. Research on the biology of skeletal muscle and its regulatory anabolic and catabolic factors is many decades old. adequate protein. proinflammatory cytokines) are absent. especially protein. In any given person and within any given physiological state. A host of factors stimulating muscle protein synthesis and degradation has been characterized. such as insulin and testosterone. and nutrients. it is not cell division and cell death that contribute to muscle mass. especially resistance-type activity (i. including tumor-derived factors. jeopardizes respiratory function. ANABOLIC COMPETENCE—THE SPORTS MEDICINE APPROACH The commonly used approach in sports for building maximal muscle mass is well known: resistance training (weight-lifting).1 FACTORS INFLUENCING MUSCLE LOSS AND GAIN The plasticity of skeletal muscle—its ability to adapt— covers a broad range. are at optimal levels and muscle is sensitized to their action Catabolic factors related to stress (i. and is associated with poor performance status and outcome.. these s Muscle mass rises to its maximum when: Contractile work is frequent. cortisol) or disease (i. proinflammatory cytokines) are present. The negative nitrogen balance underlying cancer cachexia leads to a significant wasting of skeletal muscle and other lean tissues. Stabilizing muscle loss or regaining lean tissue mass must. not just additive in their action. The approach used in sports training is highly developed. with weight loss strongly associated with shortened survival and poor response to therapy from the earliest disease stages through to advanced cancer. is related to reduced immunity. A fourth category of stimuli exists: a series of catabolic factors that mainly occur during disease or injury. and a variety of natural and synthetic hormones to provide the three strong anabolic signals to which muscles can respond. PhD IN BRIEF Should those of us involved in anticancer therapy of patients adopt the mindset of our sports medicine colleagues? The few available trials suggest that in cancer patients. addressing specific muscle groups are available in any sports training manual. which can lead to spectacular gains of muscle in some individuals.. resistance training. nutritional supplements. Skeletal muscle is terminally differentiated. and these are commercially available as amino acid and protein supple5 I  N  C: U  March/April 2004 . These fall into three major categories: muscular work/mechanical activity.e. three categories of influences combine to define muscle mass. Muscle mass falls to a minimum when: s Contractile work is limited or absent s Nutrients (especially amino acids for building muscle protein and necessary co-factors) are unavailable s Anabolic hormones. The diagnosis of cachexia is made by a history of substantial weight loss in the context of advanced disease and a physical examination demonstrating muscle wasting.New Approaches in Reversing Cancer-related Weight Loss by Vickie E. be considered primary targets of cachexia therapy. but mainly synthesis and degradation of proteins within existing cells. such as insulin and testosterone. therefore. it seems possible to conjecture that a combination therapy involving several or all of these may hold the promise of much more important gains—as seen in healthy people. While some of the interventions have been controversial.. Baracos. endocrine factors. are at low levels or when muscle is resistant to their action s Catabolic factors related to stress (i. If these observations are borne out.

Nutrition. defined as that state which optimally supports protein synthesis and lean body mass.17(suppl 1):S1-S20. et al.Integrated Interventions in Nutritional Oncology T he goal of nutritional intervention in patients with cancer is to prevent or reverse the progressive weight loss and inanition that is seen in up to 80 percent of patients at some point in their disease or treatment. Understanding and managing cancer cachexia. Elegant work has been done on the appropriate timing of protein feeding. This approach is illustrated in Figure 1 and demonstrates the importance of addressing the three primary components of intervention: nutrition. as creatine phosphate serves as an essential phosphate donor for the synthesis of ATP. and there has been little or no progress in impacting the gold standard of survival by simply addressing nutritional interventions. Ottery FD. This appreciation is addressed by Vicki Baracos. immune competence. Mazurak VC. such as liver damage and male pattern hair growth. and exercise. while minimizing other effects. as well as intermediary markers of muscle breakdown and lipid mobilization. and 3) lack of translation of any change in weight or nutritional parameters into improved oncology outcomes. Clinical significance of weight loss in cancer patients: Rationale for the use of anabolic agents in the treatment of cancer-related cachexia. Easson AM.2 Synthetic anabolic steroids derived and developed from the basic structure of testosterone have been intensified in their anabolic action on skeletal muscle. Use of pharmacoI  N  C: U  March/April 2004 . While these were initially used based on anecdotal evidence.197:143-161. A more comprehensive review of the understanding and management of cancer cachexia has recently been published by Baracos and her colleagues in Canada. treatment of cancer cachexia has focused on the provision of macro. and—insofar as it involves diet and activity—can be generally inexpensive and can be used by patients directly or coordinated by the clinician. bodybuilding competitions.4 Creatine 6 supplementation in the diet is used as an adjunct in this recipe. a critical energy source for initiating muscle activity. Hoffman JP. J Am Coll Surg. 2001. Figure 1. Until recently. Clinicians who use nutritional therapies alone to combat weight loss in cancer patients experience three common frustrations: 1) lack of consistent reversal of weight loss with intervention. 2003. The Three Primary Components of Nutritional Intervention Nutritional Milieu Optimal Composition & Physiologic Function Exercise Hormonal Milieu ©Ottery.2 REFERENCES 1Langer CJ. Unfortunately. functionality. 2MacDonald N. the level of understanding of the etiology of muscle catabolism in cancer cachexia. and football fields. During the past decade. relative to the timing and type of exercise bouts. 5-17 Evidence of the success of this integrated musclebuilding program can be seen in gymnasiums.and micronutrients to reverse weight loss. even this simple goal is rarely achieved. The sports model is simple. the hormonal milieu (including both classic hormones and cytokines). This relative lack of success can be presumed to be because of a one-dimensional approach that does not integrate nutrition into a program of comprehensive cancer care. 2) lack of repletion of lean tissue or muscle. there is an increased research database supporting the use of some and refuting others. with little clinical attention to the composition of body tissues lost or repleted. PhD. have served to re-focus research into interventional options for cancer cachexia that target the functional aspects of body composition (lean tissue)—instead of simply focusing on energy reserves (adipose tissue). and quality of life.3.1 This paradigm also addresses the more global problems of muscle and organ function.1997 ments in various combinations and forms. A paradigm of integrated intervention has been developed that supports anabolism or anabolic competence.

concept of who can exercise should be revisited. strength. Schulte and Yarasheski19 provide a pertinent example in frail elderly (76 to 92 years of age) who participated in up to three months of weightlifting.23 and chronic obstructive pulmonary disease.18 The principal cancer diagnoses were breast in females and genitourinary in males. exercise training is shown clearly to stimulate muscle protein synthesis and to develop muscle mass and functional status. Some results from clinical trials looking at reversal of muscle wasting in noncancer disease may be immediately translatable to cancer populations.24-26 Clinical researchers in cancer cachexia and anorexia can learn from the related research work of their colleagues in other disciplines. with appropriate dosing and monitoring in the context of the underlying disease. 32 percent daily. evidence from recent publications indicates that repeated exercise may enhance the fitness. amino acids. defined as a general feeling of debilitating tiredness or loss of energy. Are the “new” integrated approaches to supporting anabolism to wasting syndromes simply the application of well-established concepts? Should those of us involved in anticancer therapy of patients adopt the mindset of our sports medicine colleagues? This integrated approach of nutrition. In one study. and oncologists perceived that 76 percent of their patients experienced fatigue. Clinical research on wasting in the elderly has a I  N  C: U  March/April 2004 relatively long history and has been the focus of activity in large research centers. and most patients (74 percent) considered fatigue a symptom to be endured. 19 percent).) However. and oncologist (n = 197). Patients felt that fatigue adversely affected their daily lives more than pain (61 percent vs. even in frail elders. during the course of their disease and treatment. and anabolic agents. the significant catabolic loss of muscle is an important target for interventional consideration. What seems to be lacking is the translation of this knowledge into practice. Most oncologists (80 percent) believed fatigue is overlooked or undertreated. Research in the sports medicine area has led the way with interventions. in combination with exercise programs tailored to develop muscle mass and optimize performance. (See page 11. and quality of life of cancer patients. This finding suggests that the protein synthetic machinery adapts rapidly to increased contractile activity and that the adaptive responses are maintained. Study participants showed increased biosynthesis of myosin heavy chain and mixed muscle proteins. is to be regarded as a medical intervention. median age 65).19-21 in patients with wasting syndromes associated with AIDS.logic intervention. Some results from clinical trials looking at reversal of muscle wasting in noncancer disease may be immediately translatable to cancer populations. as do younger people. Given this background.22. A key point emerging from the research is that our Clinical researchers in cancer cachexia and anorexia can learn from the related research work of their colleagues in other disciplines. and 32 percent reported fatigue significantly affecting their daily routines. 31 percent within 7 to 52 weeks. it is important to consider that fatigue is multifactorial in etiology. primary caregiver (n = 200). APPLYING THE SPORTS MEDICINE MODEL TO PATIENTS WITH WASTING SYNDROMES Fatigue is the most distressing phenomenon experienced by cancer patients. It is possible to argue that we already have the knowledge necessary to improve muscle mass and consequently patient function and mobility— that is. RESISTANCE MUSCLE TRAINING TO BUILD MUSCLE MASS AND STRENGTH Currently literature on exercise training and muscle anabolism is very extensive. and appropriate hormonal support has already been adopted by researchers in muscle wasting in the elderly. radiation therapy (63 percent). Fifty percent of patients did not discuss treatment options with their oncologists. However. Various patients considered too frail and ill to exercise have been shown to benefit from exercise. and 49 percent more than one year ago. In addition. men with prostate cancer who were scheduled to receive androgen deprivation therapy were randomly assigned to an intervention group that participated in a resistance exercise program three times per week for 12 weeks or to a waiting list control group. and only 27 percent reported that their oncologists recommended any treatment for fatigue. we know the sports-training approach that results in increased muscle mass.27 Men in the resistance intervention group demonstrated fewer fatigue-related problems with 7 . Caregivers reported observing fatigue in 86 percent of the index patients.18 Vogelzang and colleagues used a survey designed to characterize the epidemiology of cancerrelated fatigue from the perspectives of the patient (n = 419. resistance and aerobic exercise. and a review of this literature is outside the scope of this article. Cancer treatment included chemotherapy (59 percent). More than three-fourths of patients (78 percent) experienced fatigue. such as anabolic agents. including creatine. AIDS and COPD cachexia research has been enhanced by targeted funding and is also quite active at this time. or both (24 percent). The studies have addressed patients with a variety of different cancers. 20 percent of patients received their last treatment within 6 weeks.

34. perhaps creatine may also be used adjunctively to rebuild the muscles of cancer patients. Creatine is regarded as a safe supplement for healthy people and is available over the counter in health food stores. men undergoing knee replacement. and adverse changes in serum lipids. For example. Many clinical studies report that testosterone and its analogs support muscle growth. 5-17 Increase in muscle mass may be secondary to the athlete’s ability to maintain a program of physical activity. perhaps creatine may also be used adjunctively to rebuild the muscles of cancer patients. Clinicians should question patients with an open mind regarding any aspect of complementary medicine. placebo-controlled design with repeated measures and showed improved muscle performance with seven days of administration trial. More recent studies with attenuated androgens. this lack of use stems from the tainted association with illicit use of these compounds. These patients are generally very sick in the aftermath of chemotherapy. In view of the profound suffering associated with wasting and chronic illness. also known as anabolic agents. Studies on healthy males indicate that supraphysiologic injections of testosterone or its analogs induce muscle synthesis with short-term use.31. a hypogonadal state is often present in patients with advanced lung cancer. Testosterone levels are commonly reduced in patients with severe illness. although it remains possible that creatine may have a direct effect on muscle protein synthesis. but their weight gain was also associated with improvement in lean body mass. In addition. the use of other interventions that may be used by patients needs to be addressed by clinicians caring for patients with cancer. Testosterone was identified and characterized more than 70 years ago and recognized shortly thereafter as a hormone that stimulated muscle growth. Currently.20 These data indicate that seven days of creatine supplementation was effective at increasing several indices of muscle performance.40 I  N  C: U  March/April 2004 . Creatine supplementation may be a useful therapeutic strategy for older adults to attenuate loss in muscle strength and performance of functional living tasks. These daily physical training programs reduce the treatment-related loss of physical performance in patients with hematological malignancies undergoing chemotherapy. Dimeo and coworkers 28 have produced a surprising series of reports on exercise in patients undergoing chemotherapy. as only minor 8 the possible applications of anabolic steroids in patients with catabolic losses of muscle mass.39. as well as lack of clinical studies until the past decade. A recently reported trial of oxandrolone (an oral synthetic derivative of testosterone) concluded that weight-losing cancer patients on this agent not only gained weight. Anabolic Agents. and AIDS patients is associated with improved muscle size and function. but the androgen status of cancer patients has been assessed only on a few highly selected patients.35 Testosterone replacement is simply accomplished. liver damage in both sexes. as there are few crossover studies from sports medicine to wasting disorders and additional research is clearly needed. Mild abnormalities in renal function may occur. including the functional component. yet they are able and willing to exercise. Creatine. If the issue is not raised by the clinician. should be used with with caution in individuals with renal impairment or with fragile electrolyte balance. the long-term effects of androgens. a re-evaluation of the role of anabolic steroids in these conditions is currently underway. 33. Testosterone replacement in elderly men. and if considered. The lack of reported negative effects and the consistency of the observed benefits lead to the conclusion that physical exercise may provide a low-risk therapy that can improve patients’ capacity to perform activities of daily living and improve their quality of life.activities of daily living and had a higher quality of life and higher levels of upper-body and lower-body muscular fitness than men in the control group.30-36 yet anabolic steroids have only achieved a tentative hold in medical practice aside from their use in clearly demonstrated hypogonadal states. If the sports medicine data on creatine are applicable without intense exercise programs. the patient or family may fail to include the information in any medical review. In part.12 Creatine has not been tested in cancer patients. BEYOND EXERCISE: AN INTEGRATED APPROACH In addition to the exercise interventions that have been studied in patients with cancer. Creatine is a very commonly-used supplement among athletes who believe creatine builds muscle and increases muscle energy. and in view of the very substantial improvements in the efficacy and side-effect profile of these compounds. A creatine trial including normally active older men (59 to 72 years of age) used a double-blind. including functional tests in older men without adverse side effects. The sports medicine literature is replete with trials that demonstrate that healthy individuals taking creatine achieve a significant increase in lean body mass in comparison with placebo and may also improve muscle function. have limited some of these concerns.37. and quality of life scores.38 A few studies of testosterone or anabolic agents in treatment of weight loss and inanition in patients with cancer have been carried out. Physicians have been slow to act on If the sports medicine data on creatine are applicable without intense exercise programs. evidence on this straightforward proposition is not available.29 adverse effects have been reported. enabling them to train longer and perform at a higher level. including high-dose chemotherapy with stem cell rescue. which may include virilizing in women. have discouraged their use. improved ECOG performance status.

Long-term creatine supplementation does not significantly affect clinical markers of health in athletes. Amino Acids. Med Sci Sports Exerc.This work is particularly interesting because it also demonstrated that men showed greater gains in lean body mass. suggesting that cysteine becomes a conditionally dietary essential amino acid in cancer.34. ongoing randomized trials.8:286-297. Rasmussen CJ. 5Huso ME. Calif. In: Becker KL (ed. it seems possible to conjecture that a combination therapy involving several or all of these may hold the promise of much I  N  C: U  March/April 2004 more important gains—as seen in healthy people. 2003. 1998. 92(suppl):1669-1677. While anabolic therapy directed at the lean tissues seems unlikely to be entirely successful without provision of the amino acids required for protein anabolism. Nat Rev Cancer. In the age of high technology and super-drugs. Effects of oral creatine and resistance training on myogenic regulatory factor expression. et al. An amino acid mixture containing glutamine. Curr Sports Med Rep. Los Altos. stayed weight stable. 2001. in view of the evidence of hypogonadism in patients with advanced cancer. et al. 12Juhn MS. this area of research is relatively neglected. and β-hydroxy β-methyl butyrate (a metabolite of leucine) promoted deposition of lean body mass in nonsmall cell lung cancer patients without any reported sideeffects.30:73-82.34:332-343.244:95-104.: Lange. Effects of creatine supplementation on performance and training adaptations. arginine. 6Kreider RB. if the patient so desires. Recent work of Tisdale and colleagues suggest that tumors secrete novel lipolysisinducing factors as well as potent catabolic factors specific for skeletal muscle. A subsequent placebo-controlled study of oxandrolone confirmed the results of the open label study referenced above.45 The lack of a difference in survival between treated and control groups indirectly suggests that supplemental cysteine did not enhance tumor growth. Rosene JM. others have established that important gains of weight and lean tissue are possible. with significant increases in weight and lean tissue weight at month two of a four-month study. does not necessarily address the question of tumor-derived catabolic factors. 3rd ed. CONCLUSION The few available trials suggest that in cancer patients. This approach. Clin J Sport Med. To formulate amino acid mixtures optimized to support anabolism and function in cancer patients. 7Volek JS. 1998. Mol Cell Biochem.1 The nature and mechanisms of action of these factors are beginning to be elucidated. and gained weight during oxandrolone treatment. and these will form the basis of targeted therapies. nandrolone. 2003. Melton C. Only a small number of studies look at amino acid supplementation in cancer patients. strength. then 10 or 20 pounds of tissue gain may be realizable in the context of a multimodality strategy for promoting anabolism in individuals with cachexia. Med Sci Sports Exerc.8(4):298-304.46 This proprietary product originated as a sports supplement and is currently being assessed in a number of larger. adequate protein.9 pounds) was lean body mass. if it were possible that these effectors were additive or even synergistic in their actions on muscle of cancer patients. Clinical use and abuse of androgens and antiandrogens.) Principles and Practice of Endrocinology and Metabolism. Goldfien A. is professor of protein metabolism in the Department of Nutrition Science and Oncology at the University of Alberta in Alberta. 2003. Effects of cre9 . Oral creatine supplementation and athletic performance: A critical review. Effects of creatine supplementation on muscle power. Johnston CS. Creatine supplementation influences substrate utilization at rest. 3Meyers FH. 11Izquierdo M. Canada. If these observations are borne out. the most responsive group of men gained up to 13. Baracos. 2001:1181-1187. et al. Ibanez J. Strength nutrition.244:89-94. Potential side effects of oral creatine supplementation: A critical review. J Appl Physiol. Cancer. endurance. 13Kreider RB. Gonzalez-Badillo JJ. 2002. Cachexia in cancer patients. The gonadal hormones & inhibitors. 10Juhn MS. which stems from basic muscle physiology. Tarnopolsky M. et al. 1980:393-416. and amino acid or amino acid derivative supplementation can each individually promote net gain of lean body mass and associated function. 93:2018-2022. OI Vickie E. resistance training. On the other hand. Review of Medical Pharmacology. and sprint performance. Mol Cell Biochem.40 These studies extend some of the earlier results noted with the injectable anabolic androgenic steroid. this potential solution to cancer-associated wasting may simply be too obvious or not sufficiently glamorous to have merited attention. it may be possible to ask if there is any reason not to offer testosterone replacement to patients with clinical evidence of androgen deficiency. formal assessments of amino acid requirements using current methods are much needed. 4Matsumoto AM.9 pounds over a four-month period and the majority of this (10.41-43 These data address the potential effectiveness and safety of anabolic agents in cancer-related weight loss. Med Sci Sports Exerc. 8Willoughby DS.2:189-93. Supplemental oral N-acetyl-cysteine was reported to improve quality of life and increase plasma albumin levels and body cell mass in patients with various forms of inoperable cancer. 2003. and the specific amino acids supplemented are suggested by a relatively sparse literature on amino acid utilization in tumor-bearing animals. Ferreira M. In addition. Management of muscle wasting in cancer-associated cachexia: Understanding gained from experimental studies. Philadelphia: Lippincott Williams & Wilkins. 1998. REFERENCES 1Tisdale MJ. 41-44 While many believe it is not possible to maintain weight in patients with advanced malignancy.35:923-9. Preliminary data demonstrated that when patients were stratified into those who lost weight. 7th ed. 2002. and sprint performance. 2Baracos VE. Clin J Sport Med. PhD. Oosterlaar AM. Hampl JS. including aspects that may have an anticatabolic effect. 14van Loon LJ. Effects of creatine supplementation on body composition. 9Kreider RB. Wilson M. Jawetz E. 2002.39 This result—net gain of lean body mass—is in striking contrast to the often-expressed belief that cancer cachexia is inevitable and that its progression is unstoppable. Hartgens F. et al.2(11):862-871. Tarnopolsky M.

J Med. Chest. and oncologist perceptions of cancer-related fatigue: Results of a tripart assessment survey. Cella D.13:198-226. 14th International Symposium: Supportive Care In Cancer at the combined meeting of The Multinational Association of Supportive Care in Cancer and The International Society of Oral Oncology. Von Roenn J. Fietz T. quality of life. Rosenthal DI. May 31-June 3. 38Bhasin S. Int J Sport Nutr Exerc Metab. Reid RD. Germany. Creatine supplementation improves muscular performance in older men.58:183-6 42Darnton SJ. 2003.282:E601-E607. Patient.84:2705-2711. 34Von Roenn JH. Ottery FD. D’Olimpio JT. et al. J Clin Endocrinol Metab. Chicago. June 23-26. The Fatigue Coalition. 36Sheffield-Moore M. et al. 44Von Roenn JH. Int J Sport Nutr Exerc Metab. 1999. Wolf SE. cachexia. and laboratory parameters with oxandrolone use (Poster 2176). 17Chwalbinska-Moneta J. Ottery F. Marquis K. arginine. 37Amory JK. Med Sci Sports Exerc. et al. et al. Clin Sci (Lond).12:283-8. Cleary S. Int J Sport Nutr Exerc Metab. 45th Annual Meeting of the American Society of Therapeutic Radiology and Oncology. A role for anabolic steroids in the rehabilitation of patients with COPD? A double-blind. Influence of nandrolone decanoate on weight loss in advanced non-small cell lung cancer. Courneya KS. Zgainski B. The use of an anabolic steroid (nandrolone decanoate) to improve nutritional status after esophageal resection for carcinoma. et al. 22Fairfield WP. 2002. Resistance exercise in men receiving androgen deprivation therapy for prostate cancer. Sullivan DH. Effects of testosterone replacement and/or resistance exercise on the composition of megestrol acetate stimulated weight gain in elderly men: A randomized controlled trial. Storer TW. Fesen M. et al. et al.34:537-543. performance status and quality of life (QOL) scores in cancer-related weight loss (Poster 114). 1998. Berlin. 2002. 2002. Javanbakht M. 2001. UT. et al. 2003. Discussed Poster Presentation). Effects of resistance training on the rate of muscle protein synthesis in frail elderly people. et al. Testosterone administration to older men improves muscle function: Molecular and physiological mechanisms. Dis Esophagus. and glutamine.87:2100-2106. 86:5108-5117. Oxandrolone increases weight. Wouters EF. 2003.281:1282-90. Schwartz S. Clinical significance of weight loss in cancer patients: rationale for the use of anabolic agents in the treatment of cancer-related cachexia. (suppl. Sheffield-Moore M. 39th Annual Meeting of the American Society of Clinical Oncology. Herrold J. Short-term oxandrolone administration stimulates net muscle protein synthesis in young men. randomized trial. et al. Chest. J Clin Endocrinol Metab. et al. 1999. Effects of testosterone and exercise on muscle leanness in eugonadal men with AIDS wasting. Freeling SA. 20Gotshalk LA. October 19-23. 2001. The redox state as a correlate of senescence and wasting and as a target for therapeutic intervention. Engelen MP. Ali I. October 6-10. 33Ferrando AA. fuel selection. December 4-6. Breitbart W. et al. Volek JS. Effects of endurance training on the physical performance of patients with hematological malignancies during chemotherapy. 40Von Roenn JH. Salt Lake City. 31Simons JP. Support Care Cancer. LA. Effect of creatine supplementation on body composition and performance: A meta-analysis. On-going placebocontrolled study of oxandrolone in cancer-related weight loss (Abstract 1039. Clin Sci (Lond). Blood. Hoffman JP. 35Tchekmedyian S. J Strength Cond Res. et al. Yarasheski KE.34(3 suppl 2):4-12. Grenier I. Tchekmedyian S. 2003. Urban RJ. resting energy expenditure. 2003. Clinical review 138: Anabolic-androgenic steroid therapy in the treatment of chronic diseases.11:623-8 29Ardies CM. 2002.57(2 Suppl):S283-4. 1981. and catabolic and anabolic hormones. 26 Debigare R.124(5):1733-42. and cancer therapy: A molecular rationale. Ottery F. 27Segal RJ. Cote CH. et al. Tchekmedyian S.124(1):83-9. caregiver. Staron RS. New Orleans. MA. Beneficial effects of an anabolic steroid during cytotoxic chemotherapy for metastatic cancer. et al.46:52s-63s. 2000. Am J Surg. In: Int J Radiat Oncol Biol Phys. 2002. Effect of creatine supplementation on aerobic performance and anaerobic capacity in elite rowers in the course of endurance training. J Clin Endocrinol Metab. 2001. Oral Presentation. Allar MJ.21:1653-9. 90:2166-2171. 25Jagoe RT. et al.42:143-57. 23Strawford A. 2003. Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. Schols AM. Muscle wasting and changes in muscle protein metabolism in chronic obstructive pulmonary disease. placebo-controlled. Kinscherf R. 46May PE. 2002. Hoffman R. et al. 2002.283:763-770. 24 Creutzberg EC. 2nd International Cachexia Conference. Nutr Cancer. Resistance exercise and supraphysiologic androgen therapy in eugonadal men with HIV-related weight loss: A randomized controlled trial. J Appl Physiol.) 2003. Chansky HA. J Clin Oncol.11(suppl):S111-8. 19 Schulte JN. 2003. Yeckel CW. lean tissue. Barber A. 2003. CJ. 2003. et al. 45Hack V. Chansky KL. 15Rawson ES. 32Langer 10 I  N  C: U  March/April 2004 . 16Branch JD. et al. 1999. Van Loan M. acute-phase response. J Am Geriatr Soc. Breitkreutz R. Treat M. Semin Hematol. 43Spiers AS. Mostert R. Wahlstrom JT. 1997.13:173-83. Safety of oxandrolone in cancer-related weight loss (Poster N2 3013). 2002. Dobs AS. 2003. et al. 97:215-223. 1986. Volek JS. DeVita SF. 1999. Buurman WA. Annual Meeting of the American Society of Therapeutic Radiology and Oncology. State of the art in cachexia therapy: Anabolic ateroids. Catabolic/anabolic balance and muscle wasting in patients with COPD. Barbieri T. 18Vogelzang NJ. et al. 30Basaria S. JAMA. Price LM.183:471-9.50:1698-1701. Effects of creatine supplementation and resistance training on muscle strength and weightlifting performance. IL. JAMA. 2003. Thropay J. sprint and endurance performance in humans.17(suppl 1):S1-20. Reversal of cancerrelated wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate. Cancer. Eur Respir J. 28Dimeo F. 39Tchekmedyian S. Weight loss and low body cell mass in males with lung cancer: Relationship with systemic inflammation. Boston.92:59-67. 2001. Tchekmedyian S. et al. Am J Physiol Endocrinol Metab. 41Chlebowski RT.12:433-45.atine loading and prolonged creatine supplementation on body composition. 2003. Exercise. Patients with aerodigestive tract cancer and pre-exiting weight loss: Performance status.17:822-31.104:153-62. Preoperative supraphysiological testosterone in older men undergoing knee replacement surgery. 21Lambert CP. Nutr.

This integrated approach is important from time of diagnosis through treatment and in long-term survival. combined with direct complications of chemotherapy and changes in the survivor’s hormonal milieu (orchiectomy. corticosteroids. and Regina S. Suzanne R. MD.5-11 Studies of physical exercise in cancer initially focused on aerobic exercise in women with breast cancer. Family members and clinicians frequently advise people with cancer to rest and to reduce the amount and intensity of their activities—both during and after treat- I  N  C: U  March/April 2004 . with its ensuing complications of pain and risk for compression and other pathological or traumatic fractures. PhD. again with implications for the long-term survivor. and the proinflammatory cytokines associated with malignancy. Physical inactivity can contribute to disuse muscle atrophy. Each of these settings is also associated with mobilization of bone calcium. Inactivity.”1 Optimal cancer rehabilitation techniques should focus both on the reduction of unnecessary catabolic processes (such as unnecessary activity restrictions or anemia) as well as building on anabolic processes to optimize daily functioning and quality of survivorship (QOS). and Nutrition by Faith D. Kasenic. RD. In healthy volunteers. contributing to loss of cardiorespiratory fitness and to fatigue.2-4 These changes can be exacerbated in the setting of fever.” In other words.12 More recently. these recommendations may exacerbate the fatigue that plagues the survivor. There is an increasing body of literature supporting the importance of physical exercise in cancer survivors with a variety of different cancer types with demonstrated improvement in 1) functional capacity. Ottery. significant changes—increases or decreases—in a patient’s weight or body composition are undesirable for anyone going through cancer treatment. Exercise. contraindications to hormone replacement therapy or HRT. PHYSICAL ACTIVITY AND SURVIVORSHIP “Life is a metabolic dance between anabolic and catabolic processes. improved body composition with increased lean tissue and decrease in fat mass. Catabolic losses of weight that occur as the result of cytokine-mediated changes in metabolism or chronic use of corticosteroids can also contribute significantly to loss of muscle mass during cancer treatment. physical activity (aerobic and resistance exercises). PhD. as well as improved strength and functionality. becomes increasingly important with increased survivorship—in terms of both numbers of survivors and duration of survivorship. 2) perception and measured 11 O nce. and corticosteroid use) all contribute to increased risk of progressive bone demineralization and osteoporosis. physical activity (aerobic and resistance exercises). The cornerstone for addressing appropriate body composition and metabolic balance in patients with cancer is a multimodality approach that combines nutrition. I made the comment that the initials NSABP actually referred to the phrase “Nutritional Stability Always Brings Pleasure. Structure and function of muscle and bone are dependent on physical activity combined with appropriate nutrition and hormonal milieu supporting anabolism. RN. also associated with adverse outcomes. AOCN® IN BRIEF Our perceptions of the effects of deterioration in nutritional status and body composition must expand beyond the realm of acute toxicity to one of long-term and quality survivorship. ment. living alone may actually contribute to improved functionality as well as supporting continued independence. and pharmacologic intervention as necessary. This perspective allows a consistent and integrated philosophic approach to cancer care. complete bed rest for as short as a week has been associated with a 1-4 percent loss of muscle mass and a number of metabolic changes including insulin resistance and increase in extremity fat.Multimodality Approaches to Optimize Survivorship Outcomes: Body Composition. Cunningham. and pharmacologic intervention as necessary. Resistance exercise is increasingly recognized as an important therapeutic intervention for preventing or reversing bone loss and its complications. Accelerated loss of bone mineral density. This integrated approach is important from time of diagnosis through treatment and in long-term survival. The combined losses of weight and lean tissue may be synergistic and if not reversed with cancer rehabilitation may progress further over time due to impaired physical activity. whether one is addressing a postmenopausal woman with breast cancer who is at risk for significant weight gain and potential adverse oncologic outcomes or the patients with cancers in which progressive weight loss and cachexia may be the rule. in giving a nutritional presentation to the National Surgical Adjuvant Breast and Bowel Project. The cornerstone for addressing appropriate body composition and metabolic balance in patients with cancer is a multimodality approach that combines nutrition. resistance exercise has been added to the regimens with impact on cardiorespiratory fitness. In fact.1 Interestingly.

Postgrad Med. 2003. Components as simple as the intake of adequate protein in chemotherapy toxicity and loss of muscle mass and function in individuals on bed rest to the chronic sequelae of malnutrition and body compositional change have long been underappreciated in the armamentarium of the oncologist and are now beginning to play a role as we address issues of survivorship. Cunningham. and resistance exercise (elasticized resistance bands. increase in lean tissue weight. Suzanne R. 4Stuart CA. et al.52(3):509-14. as well as recent research in multimodality intervention. all of which are with associated functional and quality of life improvements. Stuart CA.fatigue. exercise. Insulin responsiveness of protein metabolism in vivo following bedrest in humans. AOCN® is chief nursing officer and director of Ambulatory Services at the Cancer Institute of New Jersey in New Brunswick. megestrol acetate) characterizes the new model of multimodality approaches for improving quality of cancer survivorship. it is important to consider the effects of glucocorticosteroids on lean tissue and the skeleton. Am J Clin Nutr. Inc. 1988. and is probably the most common form of drug-induced myopathy encountered in clinical practice. CORTICOSTEROIDS: CHRONIC MUSCULOSKELETAL SEQUELAE Corticosteroids have a number of physiologic effects that contribute to broad use in patients receiving cancer therapy as well as in treatment of survivor co-morbidities. mood. 2001. In review of the published literature. light-to-moderate weight lifting).37(8):802-6. and 5) immunologic function as assessed by increased natural killer cell activity. Since the inception of the Association of Community Cancer Centers (ACCC) 30 years ago. Fulton MN. Baz MA. RN. 1990. Bed-rest-induced insulin resistance occurs primarily in muscle. 3) lessening requirements for medications for nausea or pain. Strategies for managing cancer-related fatigue syndrome: A rehabilitation approach. Prince MJ. and antineoplastic roles are common as well as used in terminal palliative care for its central effects to improve sense of well-being and short-term improvements in affect and appetite. adequate protein intake. Resource Support®) or β-hydroxy β-methylbutyrate (HMB) with glutamine and arginine24 (Juven®). Evolution of standardized assessment. et al. 5Braith RW. Resistance exercise training and alendronate reverse glucocorticoid-induced osteoporosis in heart transplant recipients. or nature-based programs. Prevention and treatment of corticosteroid-induced osteoporosis is based upon general measures such as calcium and vitamin D supplementation. PhD. 12 Lack of awareness regarding the impact of nutrition and body compositional changes on acute and chronic aspects of survivorship as well as a lack of awareness of cost-effective interventional options are the two greatest impediments to success in addressing acute and chronic sequelae of cancer therapy. 6Fiechtner JJ. Shangraw RE. 4) psychological or emotional aspects of improved self-esteem. REFERENCES 1Winningham ML. Fulton MN.13-19 The specific physical aspects of cancer rehabilitation can include one or more of the following: deficit-related physical and occupational therapy. 1988. Pa. Cancer. the Association has set standards of integrated quality oncology care. have been shown to increase bone mineral density and to decrease fracture rate. 3Stuart CA. Shangraw RE.92(4 Suppl): 988-997. Probably the most important aspects of a synergistic multimodality approach are 1) awareness. PhD. anticatabolic agents such thalidomide25 (Thalomide®). home-based. regardless of the underlying disease state utilizing chronic corticosteroids. MD. Table 1 addresses the specifics of this approach. The development of muscle weakness and atrophy is a well-known complication of therapy with exogenous glucocorticosteroids. In addition to effects on muscle. Kasenic. HIV. and support of an appropriate hormonal milieu. glucocorticoids also contribute significantly to bone demineralization and risk for progressive osteoporosis. stretching. Drug therapies and lifestyle modifications that can reduce risk. reduced depression and anxiety. is current chair of the Rehabilitation Committee of the Multinational Association of Supportive Care in Cancer and director of medical affairs in oncology. Am J Physiol. Resistance training prevents vertebral osteoporosis in lung transplant recipients. regular physical exercise. 7Mitchell MJ. which are potent bone resorption inhibitors. OI Faith D. The proximal muscles of the arms and legs are affected first with the lower extremities demonstrating the earliest signs of weakness.22(10): 1082-90. In the context of the current discussion. Ottery. overall sense of well-being. and 3) appropriate intervention. and now anabolic agents such as oxandrolone 26-28 (Oxandrin®) demonstrate increases in total weight or slowing of weight loss. Hip fracture prevention. 2003. cycling. There is a relative sparing of distal musculature. Metab. is oncology nutritionist at Fox Chase Temple Cancer Center in Philadelphia. Prince MJ. exercise is increasingly included as integral to any intervention addressing prevention or treatment of musculoskeletal complications of corticosteroids. et al. The patient first notes difficulty climbing stairs and rising from low chairs because hip girdle and thigh weakness. RD. Magyari PM. dancing). individual or group exercise programs. anti-inflammatory. offer new insight that is immediately applicable to the oncology team. but by the time this occurs marked muscle atrophy is evident. continued on page 14 I  N  C: U  March/April 2004 . exercise and pharmacologic intervention (oxandrolone vs. institutional. aerobic (walking. 2) assessment. et al.20-22 The clinical presentation of steroid-induced muscle weakness is characterized by an insidious onset and is usually painless. sense of control. and geriatrics for Savient Pharmaceuticals.J. Bisphosphonates. J Heart Lung Transplant. A newly launched NCI-sponsored study addressing an integrated approach of nutrition. swimming. hormonal replacement therapy and upon specific means like therapies used in primary osteoporosis. gym. N. Today the role of exercise. 2Shangraw RE. specialty nutriceutricals containing omega-3 fatty acids23 (ProSure®. and smooth muscle does not appear to be involved.114(3):22-28. 255(4 pt 1):E548-58. Peters EJ. Regina S. et al. Antiemetic. SYNERGY OF NUTRITION AND EXERCISE IN SURVIVORSHIP Support of whole-body anabolism is based on an integrated approach of nutrition. Effect of dietary protein on bed-rest-related changes in whole-body-protein synthesis.

antidepressants. fluid Body composition assessment Functionality I  N  C: U  March/April 2004 . fat. Nutritional intervention s Define macronutrient goals protein/calorie counts Protein 0. anticatabolic/antimetabolic or anabolic agents. PG-SGA* Patient history. other PG-SGA. anticatabolic/antimetabolic or anabolic agents. mineral as indicated s Consideration of commercial nutritional supplements s Consideration of specialty nutriceuticals: HMB or omega-3 Pharmacologic intervention s Antiemetics.7 g/lb of ideal weight (1. fluid Vitals. bisphosphonates. strengthresistance bands. PG-SGA.Table 1. others Patient history. orexigenic. Practical Assessments in Prevention and Treatment of Chronic Sequelae of Cancer Therapy Variable Nutritional Status Weight. analgesics. others Behavioral intervention s Mixed modality exercise (aerobic. PG-SGA Body Composition/Bone Mineral Density Physical examination: muscle. weight lifting) continued on page 14 13 Nutrition impact symptoms Catabolic/metabolic stresses Physical examination: muscle. diuretics. fat. ice. diuretics Behavioral intervention s Mixed modality exercise (aerobic. weight history Nutritional intake Assessment Intervention Scale. resistance/strength) Pharmacological intervention s Orexigenic. PG-SGA Focused physical exam. others Pharmacologic intervention s Anticatabolic/antimetabolic or anabolic agents.5 g/kg)/day Calories 16-18+ kcal/lb current weight s Micronutrient—multivitamin and vitamin. orexigenic. anticatabolic/antimetabolic or anabolic agents. parathyroid hormone. behavioral Pharmacologic intervention s Antiemetics. anthropometrics Bioelectrical impedance analysis (BIA) Dual energy X-ray absorptiometry (DEXA) Behavioral intervention s Mixed modality exercise (aerobic. concommitant meds. antidepressants. analgesics. resistance/strength) Pharmacological intervention s Orexigenic. anticatabolic/antimetabolic or anabolic agents. calcium. magnesium. vitamins A and D. PG-SGA Behavioral intervention s Address taste and smell sensory changes s CAM: ginger.

Friedenriech CM. and Therapy. diuretics. other. handgrip strength *The Patient-Generated Subjective Global Assessment (PG-SGA) tool and worksheets are for patient or clinician use. Karnofsky. Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: A randomised double blind trial. 20Mastaglia FL. 14 I  N  C: U  March/April 2004 .285(6):785-95.183:471-9. 13Courneya KS. Finke J. 2003. Effects of exercise training on fasting insulin. parathyroid hormone. other Assessment of activities of daily living Assessment of change from individual’s norm ECOG/Zubrod.33(5):503-13. Tchekmedyian S. Unpublished doctoral dissertation. Transplantation. and physical examination focused on body composition. Reversal of cancer-related wasting using oral supplementation with a combination of betahydroxy-beta-methylbutyrate. Osteoporosis prevention. PG-SGA How fast? How often? How long to recover? Borg scale of perceived exertion Endurance Strength 6-minute walk Rise from chair.accc-cancer. J Bone Miner Res. 1998. Exercise therapy effect on natural killer cell cytotoxic activity in stomach cancer patients after curative surgery. self-esteem. 27Tchekmedyian S. et al. Cancer Epidemiol Biomarker Prev.81:777-779. 1987. Ohio. et al. et al. 1982. Von Meyenfeldt MF. 18Dimeo F. health habits. Gao R. Resistance exercise prevents glucocorticoid-induced myopathy in heart transplant recipients. Kim YK. State of the Art in Cachexia Therapy: Anabolic Steroids. et al. Cleary S. et al. Columbus.18:1191-1197. Hoffman R. Med Sci Sports Exerc. Ward A. but greater insight may be obtained in terms of functionality and QOS with questions addressing change in functioning as it impacts that survivor.16(1):175-81. A pilot study of group exercise training (GET) for women with primary breast cancer: Feasibility and health benefits. Safety of Oxandrolone in Cancer-related Weight Loss (Poster N2 #3013) 39th ASCO meeting.57(2 suppl):S283-4. Strauman TJ.org/publications/pgsga.33:718-723. Drugs. An aerobic exercise program for patients with haematological malignancies after bone marrow transplantation. 2003. Roth SM. et al. Oral Presentation. and therapy. Welsch MA. insulin-like growth factors. et al. insulin resistance. The PG-SGA addresses the global status of the patient from this integrated perspective—weight loss and weight loss history. Carpinelli RN. nutrition impact symptoms. and www.18:1157-1160. 2003. 10Kerr D. et al. et al. 16Kolden GG. nutritional intake. Med Sci Sports Exerc. J Psychosoc Oncol. 2002.52(10):1479-86. 28Von Roenn JH. The Ohio State University.pdf. October 19-23.30:483-489. Chicago. ECOG or Karnofsky performance status assessments are important prognostic indicators. Tchekmedyian S.79:1181-119 23Fearon KC. 21Braith RW. 45th ASTRO meeting. anticatabolic/antimetabolic or anabolic agents. metabolic/catabolic stresses. 19Na YM. J Clin Invest. Field CJ. analgesics. arginine.24:304-321. 24May PE. 2001. 25Khan ZH. ECOG performance status in patient terms. Scheidegger JR. Mills RM. calcium.Variable Functionality continued Assessment Intervention Pharmacological intervention s Antiemetics. Hoppeler H. Relationship between exercise during treatment and current quality of life among survivors of breast cancer. D’Olimpio JT. 2001. 2003. et al. et al. 2001. Barber A. et al.org/publications/pgsgaworksheet. Mori M. Maslen B. Aliment Pharmacol Ther. Strength training in the elderly: Effects on risk factors for age-related diseases.12:721-727.30(4):249-68. Cole AT. or exigenic. 1997. 26Von Roenn JH. JAMA.15:35-57. 14Nelson JP. 11Hurley BF. Prev Med. Sports Med. 22Horber FF. 2001. et al. magnesium. Oncol Nurs Forum. and insulin-like growth factor binding proteins in postmenopausal breast cancer survivors: A randomized controlled trial. Courneya KS. Am J Surg. December 4-6. Exercise reduces daily fatigue in women with breast cancer receiving chemotherapy. Gut. Bertz H. 2000. 12Winningham ML. 2003. 8Winett RA. Impact of physical training on the ultrastructure of midthigh muscle in normal subjects and in patients treated with glucocorticoids. and perceived benefits and barriers to exercise in women who have and who have not experienced stage I breast cancer. Discussed Poster Presentation). Berlin. Perceived health. vitamins A and D.accc-cancer. 1996. From the standpoint of functionality. May 31-June 3. 2002.11:447-456. 2000. In: Int J Radiat Oncol Biol Phys. Potential health-related benefits of resistance training. Oesophageal cancer and cachexia: the effect of short-term treatment with thalidomide on weight loss and lean body mass. diagnosis. On-going placebo-controlled study of oxandrolone in cancer-related weight loss (Abstract 1039. 17Fairey AS. 15Schwartz AL. Bone Marrow Transplantation. 2003. Utah. Simpson EJ. Salt Lake City. 2nd International Cachexia Conference. Fesen M. antidepressants. et al. Adverse effect of drugs on muscle. Germany. Psychooncol. and glutamine. Arch Phys Med Rehab.76(3):557-62. Moses AG. Ackland T. Ill. bisphosphonates.pdf. Effects of a bicycle ergometry program on functional capacity and feelings of control with breast cancer. 2003.17:677-82. 2003. 1991. 1983. 9NIH Consensus Development Panel on Osteoporosis Prevention. They can be found on ACCC’s web site at www. Price LM. Diagnosis. Resistance training over 2 years increases bone mass in calcium-replete postmenopausal women. Kim MY.