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Nutrition in Cancer Care (PDQ®): Supportive care - Health Professional Information [NCI] - Tumor-induced Effects on Nutritional Status

Nutritional status can be compromised in direct response to tumor-induced alterations in metabolism. Also known as cachexia, this condition is one of advanced protein-calorie malnutrition and is characterized by involuntary weight loss, muscle wasting, and decreased quality of life.[1,2] Tumor-induced weight loss occurs frequently in patients with solid tumors of the lung, pancreas, and upper gastrointestinal tract and less often in patients with breast cancer or lower gastrointestinal cancer. Although anorexia may also be present, the energy deficit alone does not explain the pathogenesis of cachexia. Several factors have been proposed.[3] Mediators including cytokines, neuropeptides, neurotransmitters, and tumor-derived factors are postulated to contribute to this syndrome.[4] Products of host tissues, such as tumor necrosis factor-α, interleukin-1, interleukin-6, interferon-γ, and leukemia inhibitor factor, as well as tumor products that have a direct catabolic effect on host tissues, such as lipid-mobilizing factor and proteolysis-inducing factor (not established as definite in humans), have all been identified as mediators of this complex syndrome.[3] Altered metabolism of fats, proteins, and carbohydrates is evident in cancer patients with cachexia. Tumors may induce impaired glucose uptake and glucose oxidation, leading to an increased glycolysis.[5] Weight loss can occur from a decrease in energy intake, an increase in energy expenditure, or a combination of the two. Although anorexia is a common symptom of cancer patients, studies have shown that increased caloric intake either by the oral route or by supplementation with total parenteral nutrition has failed to counteract the wasting process. This supports the theory that the aberrant metabolic rate is the direct response by the tumor and the immune system to disrupt the pathways that regulate the homeostatic loop of body-weight regulation.[4]

Current studies suggest that the basal metabolic rate serves as a possible prognostic indicator of survival. As cancer progresses, the basal metabolic rate declines and cachexia occurs, reducing long-term survival.[6] Although alterations in overall basal metabolic rates have not been observed by some,[7] increased basal metabolic rates have been reported in pediatric,[8] breast,[9] lung,[8] malnourished,[10] and other [11] cancer patient populations; however, the discrepancy may be related to the stage of cancer progression.[12] Nutritional support therapies aimed at preserving lean muscle mass and subcutaneous adipose stores despite this altered metabolic rate may ultimately improve patients' quality of life and impact overall survival.

Although an individual's nutritional status may be compromised initially by the diagnosis of cancer, thorough nutritional screening procedures and the timely implementation of nutritional therapies may markedly improve the patient's outcome. Symptoms and side effects may sometimes be managed by a combination of dietary and pharmacologic interventions.

Several approaches to the treatment of cancer cachexia have been reported, and a variety of agents have been studied for their effects on appetite and weight. The decision to use pharmacological treatment to improve a patient's appetite should be based on the patient's desires, current medical condition, and life expectancy. Table 1 lists several medications that have been proposed to treat the symptoms of cancer cachexia.[13] However, the management of cachexia remains a complex challenge, and integrated multimodal treatment targeting the different factors involved has been proposed. In a phase III study, patients were randomly assigned to receive megestrol acetate, eicosapentaenoic acid, L-carnitine, thalidomide, or megestrol acetate plus L-carnitine and thalidomide. Interim analysis of 125 patients suggested the most effective treatment would be a combination regimen. The optimal combination is the goal of ongoing research.[14]

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