Cancer cachexia is a wasting syndrome in which fat and muscle are lost because of the presence of a tumor. Patients lose weight and appetite, and become weak and tired. Even when nutrition is adequate, skeletal muscle breakdown occurs, along with abnormal fat and carbohydrate metabolism. Nutritional supplementation is rarely helpful. Basic management after attempts to treat the underlying disease requires classification of possible contributing causes, including psychologic issues, eating problems, oral diseases, swallowing difficulties, stomach problems, bowel issues, malabsorption, fatigue, pain, and metabolic and functional conditions. MacDonald and associates suggest four classes of variables that potentially can contribute to cancer cachexia: anabolic deficits, catabolic drivers, human relationships with food, and nutritional deficiencies.

The former two classes are characterized by decreased quantity of and response to anabolic factors such as insulin, thyroid hormone, and testosterone, and an increase in quantity of or response to catabolic agents such as glucagon, cortisol, and proinflammatory cytokines. The body's reaction to cancer includes catabolic processes common to injury and infection mediated by proinflammatory cytokines. Common catabolic mechanisms have been found in many tumors, but there may be additional mechanisms exclusive to specific cancer types and patients. The mechanism for decreased responsiveness to anabolic factors is less clear.

Clinical therapeutic agents for cancer cachexia are being explored, but studies often are limited to a single tumor group and require corroboration. Because improved nutrition may enhance tumor growth, potential therapies must act through mechanisms that do not support tumor progression (see the accompanying table). Progestational agents such as megestrol and medroxyprogesterone acetate are easy to use and improve appetite. The anti-inflammatory effects of cardiovascular drugs (e.g., statins, angiotensin-converting enzyme inhibitors) are being studied. Macrolide antibiotics possess anti-inflammatory properties and stimulate gastric motility. Creatine, a commonly used supplement presumed to enhance muscle strength, is safe, but its efficacy in treating cancer cachexia needs further study. Anabolic agents (i.e., androgens) may be useful in cancer patients with low testosterone (except in patients with hormone-dependent tumors), but their exact therapeutic role is uncertain. Amino acid supplementation, including cysteine, may increase lean body mass. Omega-3 fatty acids such as eicosapentaenoic acid, can reduce inflammation and proteolysis. Nutritional counseling and exercise are also useful therapeutic activities.

The authors conclude that the terminal phase of cancer cachexia may be eased if patients are helped to understand the reasons for weight loss. Clarification of the causes of weight loss relieves caregivers, who associate feeding with caring. Hunger and thirst are actually rare in terminally ill cancer patients.