AUSTRALIA: Saving cancer patients from starvation

It is like watching someone starve to death: sometimes slowly, sometimes so quickly as to be shocking in its suddenness but always dreadfully painful to the sufferers and their relatives.

Half the people dying with cancer lose weight and their muscles waste away until a significant proportion of their body mass has gone. This is the impact of a condition called cancer cachexia, from the Greek meaning 'bad condition'.

So serious is the effect of cachexia on those with the disease that one in five deaths is thought to be due to the weight loss alone rather than the cancer itself, says Dr Paul Lewandowski.

Lewandowski heads a team of medical researchers at Deakin University in Melbourne working on a treatment for the debilitating loss in weight and muscle wasting condition. He says cachexia not only has an impact on quality of life for cancer patients but it also inhibits the effectiveness of cancer treatments such as chemotherapy and radiotherapy.

"One in three of us will contract cancer during our lifetimes and one in six will suffer from cachexia yet there is currently no effective treatment and it is often an unrecognised health issue," Lewandowski says.

The researchers - the team also includes PhD students Edward Hinch and Vannessa Vaughan, Deakin University postdoctoral fellow Melanie Sullivan-Gunn, and Barwon Health's regional director of palliative care, Associate Professor Peter Martin - are testing two readily available therapies, separately and in combination, which they believe could delay the onset of cachexia.

One is fish oil containing an omega 3 fatty acid and the other is a drug called oxypurinol, a 'new generation' version of the anti-gout medication alopurinol that has been used for more than 50 years.

"Cachexia commonly affects older patients whose quality of life is dramatically reduced. They don't feel like eating and can't exercise because they are constantly tired and lethargic," Lewandowski says. "Our hope is that the treatment we are working on will delay the onset of cachexia or slow down its progression and this could buy time for other cancer therapies to have an effect."

He says scientists do not fully understand the cause and development of cancer cachexia although an imbalance of chemicals known as free radicals in the cancer patient's body is thought to play a major role. Restoring the balance of free radicals is the focus of the Deakin study.

Free radicals occur naturally in the body and are not harmful at low levels. Under normal circumstances, Lewandowski says they are kept under control by antioxidants but, with cachexia, the balance is tipped and the free radicals cause serious damage to the body's DNA and proteins.

'"Protein production drops significantly while at the same time protein breakdown is dramatically increased. Muscle wasting is the inevitable outcome."

He says oxypurinol suppresses a free radical-producing enzyme believed to be overactive in patients with cachexia. The omega 3 fatty acid, known as EPA, has two modes of action: it reduces inflammation, and in some cases slows tumour growth, while also increasing the activity of the antioxidant enzyme so reducing free radical levels in the body.

"My research group has an interest in dietary anti-oxidants and how they can be used in nutritional therapy to treat conditions where there are increased levels of free radicals," Lewandowski says. "With conditions such as cancer cachexia there is an increase in free radicals but to try to come up with therapies we need to understand some of the underlying mechanisms."

The researchers began their investigations using mice they could infect with colon cancer. They had two strains of the cancer, one that did not cause cachexia in the little animals and the other that did, so the first could serve as a control in the experiments.

"We wanted to develop a mouse model because that way we can produce cachexia in a reliable fashion," Lewandowski says. "It is very important when testing novel therapies that we know how the disease behaves and we like to have the model as proof of concept to begin with before we undertake a human trial so we can be confident the therapies we've tested are working reliably."

Mice with the aggressive cachexia-causing colon cancer began to lose weight after 17 days and by day 29 they had lost up to 25% of their original body weight, along with a significant drop in their muscle mass and in the size of the heart as well.

"To test how effective the therapy is we monitored the body weight of the animal and at the end of the trial, when the mice had been killed, we also measured the weight of their organs," Lewandowski says.

"In one experiment, we waited until cachexia was occurring in the animals and then started treating them. But the really positive results occurred when we gave them oxypurinol or EPA before we induced the cancer.

"That was when we saw significant improvements in delaying the onset of weight loss while the final body weight of the animals was significantly greater than of those that did not have the therapy."

He says neither the cancer nor the two chemical substances had any significant effect on the appetites of the mice and they consumed the same amount of food before and during the trials. Testing EPA and oxypurinol separately and in combination showed that EPA seemed more effective on its own and in combination than just oxypurinol by itself.

Having completed the experiments with mice, the researchers plan to start a three-month trial later this year or early next with a pilot group of 20 volunteer patients suffering from cachexia. The patients will take fish oil supplements while undergoing other treatments for their cancer.

"I don't know if we will be able to cure the cachexia but if we can slow its onset that would be a good outcome," Lewandowski says.

geoff.maslen@uw-news.com