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Cachectic process

Cancer cachexia is a multifactorial process resulting in increased energy expenditure, anorexia, protein breakdown and severe weight loss.
Pro-inflammatory cytokines increase protein and fat breakdown, increase energy expenditure and cause anorexia.
The pro-inflammatory cytokine interleukin-6 activates the acute phase protein response (APPR). This results in increases in the concentration of C-reactive protein, fibrinogen and a-1-antitrypsin and decreases in the concentration of albumin, prealbumin and transferrin.
Hormone levels of cortisol and glucagon are increased and insulin is decreased.
Muscle protein is degraded as levels of proteolysis inducing factor (PIF) and ubiquitin-proteasome rise. These changes happen even before weight loss is observed.

Cancer-induced weight loss - from molecular mechanisms to practical solutions

Delegates heard from Dr Maurizio Muscaritoli, associate professor of internal medicine, Department of Clinical Medicine, University La Sapienza, Rome, Italy, about the huge impact that cancer has on people's lives. 'It affects one out of every four people and causes five million deaths worldwide. Cancer-induced weight loss is often the presenting symptom and is experienced by 80% of cancer patients. One million people die each year because of cancer-induced weight loss'.

'Proteolytic activity in the muscle of gastric cancer patients is 500 per cent more than in healthy controls⁵ and studies have shown that muscle ubiquitin-mRNA levels are raised in gastric cancer patients even when patients have lost little or no weight⁶. This indicates that the molecular mechanisms involved in cachexia are operating very early on during neoplastic disease.'

Presenting two case studies which showed that cachectic patients with pancreatic cancer and bladder cancer benefited from specialised, EPA-containing nutritional supplements, Dr Muscaritoli concluded that both oncologists and nutritionists should start considering cancer cachexia as an early phenomenon.' Specialised nutritional and metabolic support should become part of the standard of care for cancer patients, and should be started early after diagnosing cancer, even before the onset of body weight loss,' he said.

Cancer patients more active on ProSure^®

As cancer specialists and dietitians from around the world increasingly recognise the importance of optimising nutrition in patients with advanced disease, there was a much-needed focus on palliative care at the 25th European Society for Parenteral and Enteral Nutrition (ESPEN) Congress in Cannes, France, September 20-23, 2003. See ESPEN.org.

Cancer patients who take the eicosapentaenoic acid (EPA)-enriched nutritional supplement, ProSure^®, do not just gain weight, they are also more physically active. This is what Professor Ken Fearon, Edinburgh Royal Infirmary, Scotland, told a packed lecture entitled New therapeutic advances in the management of cancer-induced weight loss. He presented some of the first objective data to show that it is possible to use nutritional methods to influence the quality of life of cancer patients with cachexia.

In a sub-group of patients from the large placebo controlled trial of ProSure^® in advanced pancreatic cancer, those who took the EPA-enriched supplement for eight weeks had significantly higher physical activity scores than at the start of the study. But no comparable increase was seen in those who took a placebo. In the ProSure^® group, the mean Physical Activity Level (PAL) increased from 1.3 at baseline (a score typically seen in someone who is mainly bed-bound) to 1.5 (p=0.005) – a normal score for someone who has a largely sedentary lifestyle.³

'What we're looking for is better function from patients and we know from these data that we're starting to achieve it,' Professor Fearon told delegates. 'Two of the biggest concerns for patients facing terminal illness are financial concerns and the impact of their cancer on their quality of life. We can't solve patients' financial problems, but we can affect their physical activity – whether that means getting up and about, going to hospital for treatment, or visiting their family. Physical activity is a very effective tool for measuring the effectiveness of what we're doing.'

The multicentre study of EPA-enriched nutritional supplementation in a total of 200 pancreatic cancer patients showed a significant link between plasma EPA levels and weight gain and lean body mass⁶. Professor Fearon hoped that oncologists and surgeons will be more positive towards cancer cachexia in the light of the new results.

'There's a perception that nothing can be done for these patients. If you can't treat their cancer, there's no point in doing anything else. But I hope these results will bring more enthusiasm to treating cachexia,' he said.

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Reference

Barber MD, Ross JA, Voss AC, Tisdale MJ, Fearon KC. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. Br J Cancer. 1999;81:80-86.
Fearon KCH, von Meyenfeldt MF, Moses AGW, et al. Effect of a protein and energy dense, n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut. 2003;52:1479-1486.
Moses AG, Slater C, Preston T, et al. Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by energy and protein dense oral supplement enriched with n-3 fatty acids. Br J Can. 2004;90:996-1002.
Falconer JS, Fearon KCH, Ross JA, et al. Acute-phase protein response and survival duration of patients with pancreatic cancer. Cancer 1995:75:2077-2082.
Bossola M, Muscaritoli M, Costelli P, et al. Increased muscle ubiquitin mRNA levels in gastric cancer patients. Am J Physiol Regul Integr Comp Physiol. 2001 May;280(5):R1518-23.
Bossola M, Muscaritoli M, Costelli P, et al. Increased muscle proteasome activity correlates with disease severity in gastric cancer patients. Ann Surg. 2003 Mar;237(3):384-9.

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