Costs and Benefits of Nutrition Support in Cancer
Costs and Benefits of Nutrition Support in Cancer
Anorexia and weight loss are very common in patients with cancer
[1-3]. As an extension to a previously reported study , we
analyzed the prevalence of decreased appetite, decreased food
intake, and weight loss in 644 consecutive mostly ambulatory cancer
patients at our outpatient cancer care center in Long Beach, California.
We also determined whether patients were underweight, overweight,
or within their calculated body weight range, utilizing standard
tables as previously published . Patient characteristics are
shown in Table 1 and the results of the study are outlined in
More than half of the patients had decreased appetite or food
intake, about half were underweight, and three quarters had some
degree of weight loss. More than a third of patients had weight
loss of 10% or more from their pre-illness usual body weight.
These findings were true for patients at all stages of disease,
and overall, 59% of patients had weight loss of more than 5%.
Anorexia and weight loss is also common in AIDS patients [5-8].
In these patients, weight loss is more prominent during periods
of intercurrent secondary infections [9,10].
Significant weight loss is associated with a poorer prognosis
in both cancer and AIDS patients [11,12]. The loss of weight is
almost always associated with anorexia and decline in caloric
intake, with a reduced frequency and amount of food intake. The
cause of anorexia and weight loss may be related to the action
of various cytokines, such as tumor necrosis factor, gamma interferon,
and interleukins 1 and 6, which have effects both on the central
nervous system and peripheral sites, such as liver, adipose tissue,
and muscle [13,14].
From a quality of life perspective, the clinical significance
of anorexia in cancer and AIDS patients is that it is associated
with physical discomfort and a decline in functional status. Patients
complain of profound lack of appetite, nausea, fatigue, changes
in body image with progressive generalized wasting, and ongoing
decline in their ability to carry on their usual daily activities.
In patients with cancer anorexia, we have shown that changes in
appetite correlate well with changes in food intake, weight, and
quality of life . Utility measures applied to patients whose
health state is impaired by anorexia would be helpful in quantitating
the importance of this problem.
One approach to measuring nutrition-related concerns and the importance
of these concerns to patients with cancer or AIDS is that of Cella
et al through an anorexia/cachexia subscale added to the Functional
Assessment of Cancer Therapy (FACT) Quality of Life scale .
To better determine the significance of nutrition-related problems
to patients, a last item asks "how much do these additional
concerns affect your quality of life? "
As indicated in other articles in these proceedings (eg, those
by Jane Weeks and Jeanne Mandeblatt), quality of life measures
are not true utility measures. Although the former provide clinically
valid and helpful information, the latter would be ideal for quantitating
the impact of nutritional interventions on quality-adjusted life-years
(QALYs). Since it is generally accepted that nutrition support
per se does not prolong survival time of patients with advanced
cancer, any favorable impact on QALYs would depend on improvements
in the quality of life.
A brief history should include pre-illness weight, height, rate
of weight loss prior to evaluation, estimates of caloric and protein
intake, and presence of anorexia, nausea, vomiting, diarrhea,
dysphagia, or other specific ingestive, metabolic, or absorptive
problems . Ideal body weight can be calculated using standard
tables and compared to actual weight . Albumin levels are
usually performed as part of routine chemistry panels, and are
helpful in defining the severity of undernutrition.
Laboratory parameters specifically designed to study the nutritional
status of patients with cancer or AIDS-related anorexia and weight
loss are unnecessary, adding expense but little helpful information
to the assessment. A commonly ordered laboratory test is prealbumin,
which has a short half-life of 24 hours. Although low prealbumin
levels will confirm that the patient is undernourished and has
poor intake, the clinician ought to question whether it provides
any additional information that warrants the expense incurred
with the test.
It is our practice to have all patients at risk of malnutrition
evaluated by the team dietitian. During the first encounter, the
dietitian determines further the patient's nutritional status
and needs, and provides the patient with appropriate counseling.
Counseling: The benefits of initial and follow-up evaluations
and counseling by a registered dietitian, preferably in the context
of a team approach, can be enormous, although difficult
to quantify . The main benefits relate to patient satisfaction,
nutrition improvement or maintenance, compliance with team or
institutional management protocols and guidelines, and a judicious
use of risky and expensive treatments. The costs of nutritional
counseling are modest when compared to other interventions. (Table
Food Supplements: Liquid concentrated food supplements
provide high concentrations of calories and proteins as well as
low-volume nutrients, and are reviewed elsewhere . Instant
Breakfast and milk provide an inexpensive and usually well-tolerated
alternative. Commercial products may be more convenient and better
tolerated in those patients with lactose intolerance. Dietitians
will help patients select products on the basis of tolerance and
palatability. These products are particularly helpful when patients
cannot maintain an adequate intake through a regular diet, but
are able to swallow and have a relatively intact gastrointestinal
Appetite Stimulants: Several drugs have been tested to
see if they will stimulate the appetite of patients with AIDS
or cancer and anorexia [8,13,18]. Two drugs (megestrol acetate
[Megace] and dronabinol [Marinol]) have been approved by the Food
and Drug Administration recently for use in patients with AIDS
and weight loss. In addition, corticosteroids have been used in
cancer patients with end-stage disease for short-term (3 to 4
weeks) effects on appetite and well-being. Anabolic steroids are
also often utilized for this purpose, especially in AIDS patients,
although proof of their efficacy is lacking.
Megestrol Acetate: This orally active progesterone hormone
derivative is available in the form of an oral suspension and
was recently approved for use in patients with AIDS-related weight
loss. In these patients, two randomized placebo-controlled clinical
trials indicate that megestrol acetate can stimulate appetite,
food intake, and weight gain with associated patient-reported
improvement in an overall sense of well-being and quality of life
parameters [19,20]. Maximum weight change is seen in 2 to 6 weeks
in about one quarter of patients, but it is not achieved until
after 10 weeks of therapy in more than one third of patients .
The effects on appetite and weight are dose-related and sustained
as long as the medication is continued. Four previously published
randomized double-blind, placebo-controlled trials in patients
with advanced cancer, anorexia, and weight loss, demonstrated
substantial appetite enhancement in patients receiving megestrol
The benefits of megestrol acetate are related mainly to a favorable
symptomatic effect that results in improved appetite, food intake,
sense of well-being, and quality of life parameters. This hormone
derivative is well-tolerated and side effects are infrequent and
probably dose dependent. Side effects reported include impotence,
vaginal spotting, and deep vein thrombosis.
In the largest AIDS trial, impotence was a reported side effect
in 3% of placebo patients and in 4%, 6%, and 14% of megestrol
acetate patients receiving 100 mg/d, 400 mg/d, and 800 mg/d, respectively.
Deep vein thrombosis was reported in one patient out of 232 receiving
megestrol acetate. Although thrombotic complications have been
infrequent, a trend for a dose-related increase in thromboembolic
events has been reported in cancer patients . The weight-gain
seen with megestrol acetate is due to increased body mass, and
is not due to edema [19,23]. Charges according to drug dose are
shown in Table 3.
Dronabinol: This marijuana derivative has been in use as
an antiemetic and was recently tested in a randomized double-blind
placebo-controlled trial in patients with AIDS-related anorexia
and weight loss . Patients receiving dronabinol reported improved
appetite and mood compared to placebo. There was no significant
effect on body weight. Adverse events consisted of euphoria, somnolence,
dizziness, and confusion. No randomized clinical trials have been
so far reported in patients with cancer. Charges correlated with
dosage are listed in Table 3.
Prednisone: This and other corticosteroids have
been used for some time by oncologists as appetite and mood enhancers
in patients with end-stage disease and very poor short-term prognosis.
Randomized trials in cancer patients have shown a short-lived
(usually 4 weeks) period of appetite enhancement, without weight-gain
[27-30]. Corticosteroids are generally contraindicated in patients
with AIDS because of their immunosuppressive effects, and therefore
have not been tried as appetite enhancers in this disease. Side
effects of corticosteroids are common and can be serious. They
include immune suppression, dysphoria, insomnia, hyperglycemia,
muscle weakness, cushingoid features, edema, hypokalemia, and
gastrointestinal intolerance. Charges for prednisone are low and
are shown in Table 3; however, the true cost of using this drug
may be higher than that shown in Table 3 because of the need for
laboratory tests to monitor glucose and potassium levels, and
expenses related to potential complications.
Other compounds such as cyproheptadine and hydrazine sulfate
have been tried and shown to be ineffective in patients with cancer-induced
anorexia/cachexia [31-33]. Anabolic steroids are often prescribed
in patients with AIDS-related weight loss. However, there are
no formal clinical trial data to support their use in cancer or
AIDS-related weight loss unless there is endocrinologic evidence
of male hypogonadism. This subject is worthy of further study,
and the cost of androgenic hormones is generally modest.