PHILADELPHIAPancreatic cancer patients usually lose 25% of
their body mass within 4 months of diagnosis and die within 6 months.
But early work from Scotland on supplementation with eicosapentaenoic
acid (EPA) seems to suggest that the fatty acid may stabilize weight
and add months to the lives of pancreatic cancer patients.
David Whitcomb, MD, PhD, chief of gastroenterology, hepatology and
nutrition, University of Pittsburgh Medical Center, reviewed the
studies at the Society for Nutritional Oncology Adjuvant Therapy
annual congress. Dr. Whitcomb, who did not take part in the studies,
said he has been encouraged by his own clinical experience with EPA.
Cachexia is a marked feature of pancreatic cancer, he said.
Patients have both a loss of body mass and a loss of muscle. In
addition to not eating, they will have an accelerated catabolism, and
that leads to an early demise.
One of the reasons for the cachexia, he said, is anorexia. Pancreatic
cancer patients may be depressed, anxious, tired, and in pain,
particularly when they eat. They have maldigestion because their
pancreatic enzymes are not being delivered. They have problems with
gastric emptying and bowel obstructionso they often avoid
eating. These patients also experience early satiety and have a
markedly elevated resting energy expenditure, he said. To show
you what were dealing with, 85% to 90% of pancreatic cancer
patients have cachexia at the time of diagnosis, Dr. Whitcomb
said. Patients typically expire soon afterward, and its
not necessarily from tumor burden. Most are gone within 6
Yet in one of a series of phase I studies of EPA supplementation in
pancreatic cancer performed at the University of Edinburgh, several
patients with unre-sectable pancreatic cancer who received EPA lived
longer (Barber MD et al: Br J Cancer 81:80-86, 1999).
In Scotland, as in most parts of the world, Dr. Whitcomb pointed out,
pancreatic cancer patients receive supportive care rather than
chemotherapy or radiation therapy, so the patients in these studies
did not experience chemotherapy-induced nausea.
Twenty patients with unresectable pancreatic adenocarcinoma received
EPA supplementation. They had significant weight gain at both 3 weeks
and 7 weeks. Their weight suddenly stabilized and in some
instances increased with an EPA-supplemented diet, Dr. Whitcomb
said. Some patients were still alive 18 months after the study
started, he added.
EPA is a 20-carbon fatty acid and a major component in fish
oil. It seems to be important in a variety of things, including
membranes, receptors, and enzyme function. In pancreatic cancer, it
appears to have additional anticachectic actions for reasons not
completely understood but that may have to do with protein
catabolism, he said.
The hypotheses of the Scottish studies was that fish oil and EPA
would stabilize weight by suppressing metabolic
changes in cancer, and that the provision of additional calories with
EPA might allow weight gain in these patients. The nutritional
supplement was a solution containing 300 kilocalories, a balance of
protein, carbohydrates, and fat made up of EPA and docosahexaenoic
After 3 weeks of supplementation, the patients, who had been losing
2.9 kg a month, had a median weight gain of 1 kg. By 7 weeks, the
median weight gain was 2 kg. It was not edema, Dr.
Whitcomb said. The percentage of total body water was almost
completely unchanged. There was a gain in lean body mass and a slight
increase in fat mass.
At the beginning of the study, patients had a negative nitrogen
balance and later they had a positive nitrogen balance. On
average, there was marked improvement, he said.
There was also some improvement in resting energy expenditure and
food intake. Patients who had elevated proteolysis-inducing factor
(PIF) at the beginning, after 3 weeks had a marked PIF reduction.
Levels of the cytokines inter-leukin-6 (IL-6) and tumor-necrosis
factor (TNF) also fell with EPA treatment.
The supplementation also had a beneficial effect on insulin
resistance after meals as well as on the resting and fasting state,
he said. Many of the patients Karnofsky performance status also
In these early phase I studies, the supplements were well tolerated.
There were no major side effects identified, and, most
important, there was a change in pattern from significant weight loss
to significant weight gain, Dr. Whitcomb said. So in
patients on a rapid downhill course and well advanced in their
disease, a dietary supplement that is enriched in EPA seems to have a
A Personal Experience
On a personal note, Dr. Whitcomb revealed that he had treated a
relative with metastatic pancreatic cancer, who later died of the
disease, and had supplemented the patients diet with EPA.
For a time, it helped, he said. He had a marked
improvement in weight, and lived 10 months past his diagnosis. He
died of widespread tumor burden and fever, but he did not die of
cachexia and was able to take other chemotherapy. So with the
scientific data and the personal data, I think this is something that
warrants further investigation.