Use of EPA Improves Cachexia in Patients With Pancreatic Cancer

PHILADELPHIA—Pancreatic 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 obstruction—so they often avoid eating. These patients also experience early satiety and have a markedly elevated resting energy expenditure, he said. “To show you what we’re 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 it’s not necessarily from tumor burden. Most are gone within 6 months.”

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 acid (DHA).

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 improved slightly.

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 good impact.”

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 patient’s 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.”