Prevalence and Prognostic Implications
The prevalence of anorexia and weight loss in most oncology practices is quite high. Tchekmedyian and others explored the prevalence of cancer-associated weight loss and anorexia in an out-patient oncology setting.2 Over half of the 644 ambulatory oncology patients who were surveyed suffered from a failing appetite, decreased oral intake, or weight loss of greater than 5% pre-morbid weight.These prevalence rates may be even higher if one surveys non-ambulatory patients with late-stage disease.
In addition to being prevalent, this syndrome is associated with a poor prognosis. In a multiinstitutional, retrospective assessment of 3,047 cancer patients from 12 clinical trials, loss of more than 5% of pre-illness weight was associated with a shortened survival.3 This predictive capability of weight loss occurred independently of stage of disease, tumor histology, and performance status.There was also a trend towards lower rates of tumor response with chemotherapy in patients with weight loss. Further data have suggested that emaciation may be a direct cause of death. In a retrospective study of autopsies in 486 cancer patients, a wasted, emaciated state was the only identifiable cause of death in 1% of the patients.4
Pathophysiology of Cancer - related Anorexia and Weight Loss
Reduced Caloric In take
Poor oral intake contributes to the weight loss observed in cancer patients. In one study of lung cancer patients, it was demonstrated that caloric intake was significantly lower (approximately 300kcal/day) in weight-losing patients than in patients who did not experience weight loss.5 The decreased nutrient intake and resulting weight loss can be attributed to a variety of factors, including alterations in taste and smell; chemotherapyor radiation-induced anorexia, esophagitis, nausea, and vomiting; decreased oral intake secondary to dysphagia or abdominal pain; and early satiety due to an abdominal mass, ascites, or splenic enlargement. Malabsorption resulting from tumor involvement of the gastrointestinal tract or prior intestinal resection may also contribute to weight loss.
Alterations in Basal Energy Expenditure and Body Composition
Decreased caloric intake alone does not account for the profound weight loss observed in cancer patients. Superimposed on insufficient oral intake are complicated metabolic abnormalities that lead to an increase in basal energy expenditure, which results in an energy imbalance with subsequent weight loss.6 Elevations in basal energy expenditure have been observed in patients with lung cancer – even those with early-stage cancer7 – blood malignancies, and sarcomas.5,8,9 In one series of 100 patients with newly diagnosed lung cancer, 74% had elevations in basal energy expenditure.5 This finding is in contrast to what occurs in a starving state, where basal energy expenditure drops with food deprivation.
The changes observed in basal energy expenditure underscore the fact that cancer-associated weight loss, characterized by a disproportionate loss of lean tissue, is a distinct entity from starvation. In a study of 50 cancer patients, Cohn and others assessed body composition with a variety of sophisticated techniques and compared results with those observed in age- and sexmatched controls.11 Weight-losing cancer patients appeared to have lost both fat and lean tissue, but the loss of lean body tissue, particularly skeletal muscle, was the more striking feature. This pattern is in contrast to starvation, in which fat is lost and lean tissue is better preserved.10 In addition, only starvation – not cancerrelated cachexia – can be reversed with caloric supplementation.12
Alterations in Nutrient Metabolism
Changes in nutrient metabolism may play a role in cancer-related anorexia and weight loss. Many patients have a variety of metabolic abnormalities such as hyperglycemia, hypertriglyceridemia, and an exaggerated insulin response to glucose load.13 These changes may result from increased cytokine release in the setting of malignancy.14,15 Protein metabolism is altered as well, with increased protein breakdown resulting in enhanced amino acid release from skeletal muscle, despite the underlying reduction in muscle mass.16
The Role of Cytokines and Other Mediators
A number of studies have focused on the mechanisms underlying the metabolic changes observed in cancerrelated anorexia and weight loss. Based on these studies, there may be an important role for cytokines as well as several tumor-derived substances.