COLUMBUS, OhioPatients with cancer cachexia have been
successfully treated in a small clinical trial with the oral
administration of a high-calorie nutritional supplement combined with
eicosapentaenoic acid (EPA), a polyunsaturated fatty acid derived
from fish oil, Kenneth C. H. Fearon, FRCS, said at the Society for
Nutritional Oncology Adjuvant Therapy (NOAT) annual congress.
This combination of supplements resulted in net weight gain rather
than simple weight stabilization. The dietary supplements are
now the subject of a randomized trial of 80 patients, said Dr.
Fearon, a reader in surgery, Royal Infirmary of Edinburgh. His
groups goal is to address the metabolic changes that underlie
the weight loss and muscle wasting of patients with cachexia while
also providing them with conventional nutritional support.
In a study of 20 cachectic patients with advanced pancreatic
cancer, patients were asked to drink two cans per day of an oral
supplement combined with EPA, Dr. Fearon said. The EPA was in
the form of mixed marine triglycerides. Each 8-oz can of the oral
supplement contained 310 kcal, 16 g of protein and 1.09 g of EPA.
Drinking two cans a day, therefore, resulted in a dietary increase of
about 600 kcal, 32 g of protein, and 2 g of EPA. The total fat
increase was 6.5 g.
This drink was an addition to the patients diet and did not
take the place of other calories. The oral supplement is not
After 3 weeks of taking this supplement, average weight gain was 1
kg. The patients dramatically increased their lean body
weight, Dr. Fearon said. He emphasized that water retention was
not responsible for the weight gain. After 7 weeks, average weight
gain was 2.5 kg. Patients noted a significant trend of increase
in appetite, he said.
The nutritional supplement also seemed to inhibit the hypermetabolism
that is a frequent component of cachexia. By arresting anorexia and
metabolic change, it led to a reversal of cachexia.
This type of result has never been achieved before with oral
supplements, Dr. Fearon said. NOAT president Daniel Nixon, MD,
agreed. This is the very first time lean body mass has been put
back on a cachectic patient, he said during the question period.
A Multifactorial Problem
Cachexia, which means poor condition in Greek, is characterized by
weight loss, anorexia, early satiety, fatigue, anemia, and edema.
Body fat mass is reduced 85%, and muscle protein is reduced 75%.
Cachexia differs from simple starvation, however, in that
non-muscle mass is relatively unaffected, Dr. Fearon said. In
simple starvation, muscle mass and non-muscle mass waste similarly.
The weight loss of cachexia is caused by increased energy
expenditure, reduced food intake, or a combination of the two.
Cachexia is a multifactorial problem that needs a
multifactorial approach, Dr. Fearon said. The precise
metabolic alterations that underlie weight loss and muscle wasting
are poorly understood, he said. The dominant mechanism in
cachexia, which seems to vary among patients and tumor types, is a
raging question in medical science, he added.
In animal models, the action of cytokines has been implicated in the
development of cachexia. The University of Edinburgh group
hypothesizes that the metabolic abnormalities seen in cachexia are
caused by pro-inflammatory cytokines interacting with neuroendocrine
catabolic factors. The cytokines may be produced by the tumor cells
themselves or by the tumor host. However, investigators have been
unable to target one dominant cytokine.
An acute-phase protein response (APPR) is a biomarker for the
production of pro-inflammatory cytokines and for the hypermetabolism
seen in cachexia. Earlier studies by Dr. Fearons group showed
that an APPR is a useful predictor of survival in patients with
unresectable pancreatic cancer. The group hypothesized that the
metabolic disturbances associated with an APPR might be a worthwhile
therapeutic target (Falconer JS et al: Cancer 75:2077-2082, 1995).
Fifty years of research had shown that giving cachectic
patients more food to eat failed to reverse weight loss, Dr.
Fearon said. His group set out to improve the efficacy of
conventional nutritional food support.
A Series of Experiments
In one experiment, he said, the group gave fish oil capsules to 18
pancreatic cancer patients who had lost, on average, 16% of their
body weight. The capsules, known as MaxEPA, contained EPA and
docosahexaenoic acid. The administration of 12 g/day of MaxEPA was
shown to stabilize weight loss or even result in weight gain in the
majority of patients (Wigmore SJ et al: Nutrition 12(suppl
After this experiment, the University of Edinburgh group hypothesized
that EPA was the anticachectic agent in fish oil. It appears that EPA
acts, in part, by downregulating the pro-inflammatory cytokine
release and the APP response.
The group then did another series of experiments showing that
patients who received high-purity EPA for a month had a significant
decrease in their levels of serum C-reactive protein, an acute-phase
The next step, the one that resulted in the current experiment, was
to give additional calories along with the EPA in order to facilitate