Cachexia is a complex condition characterized by progressive weight and muscle loss, fatigue, and poor functional performance.
It interferes with the routine activities of the patient and is usually resistant to normal therapies. Cancer cachexia becomes worse over time leading to an impoverished quality of life.
Cachexia - a metabolic syndrome - occurs in stages, namely, mild, moderate, and severe. These are based on the level of calorie intake, loss of weight and of muscle, and functional ability.
In the early stages, there is only a slight loss of appetite and weight. As patients move into the moderate stage, more muscle and weight loss becomes obvious, along with a decreased appetite.
In the severe stage of cachexia, muscle wasting is very evident and patients may find it extremely difficult to perform even routine tasks.
Management of Cachexia
Cachexia treatment today mainly involves effective and adequate treatment of the underlying disease. Unfortunately, caloric supplementation does not reverse cachexia. However, other treatment approaches including nutritional counseling, with or without the use of appetite stimulants such as corticosteroids and progestational agents, have been found to mitigate the effects of cachexia.
Nutritional counseling by dietitians, physicians, and nurses is highly recommended in cachexia patients. Usual recommendations include frequent and small meals, avoiding spicy foods, and eating a heavy breakfast and light dinner. Patients should not be exposed to the aroma of cooking foods, so that they may enjoy the food better. Many studies that focused on the effect of dietary counseling observed improvements in the quality of life and reduction in the side effects of therapy in cancer patients who received this intervention.
The first clinical trial using corticosteroids to stimulate appetite in individuals with end-stage cancer cachexia was performed in the 1970s at the Mayo Clinic. The trial showed that corticosteroids are capable of stimulating appetite in these patients. Other studies that were conducted to test the effect of various doses of corticosteroids have reported similar results. The corticosteroid usually used in a clinical set up is dexamethasone. Although the long-term use of corticosteroids is associated with toxicities such as peptic ulcer disease, myopathy, hyperglycemia, and adrenal suppression, these are often not relevant concerns in many patients suffering from advanced cancer cachexia, because they may not survive long enough to develop these adverse reactions.
Progestational agents such as medroxyprogesterone and megestrol have been found to help with the stimulation of appetite and weight gain in cachexia patients. These drugs were fast-acting and were also good antiemetics. Even though high doses of these agents may produce adrenal suppression, they do not cause side effects such as myopathy or peptic ulcer disease, which are usually seen with the use of corticosteroids. However, progestational agents do increase the risk of thromboembolism, in contrast to corticosteroids.
Studies using megestrol showed that increasing doses ranging from 160 to 800 mg/day were associated with increased appetite stimulation. In the US, it is considered reasonable to begin with a dose of 400 mg/d of liquid megestrol, which is relatively less expensive when compared to the tablet. This may be increased up to the maximum dosage of of 800 mg/day, depending on the presence of side-effects or the adequacy of the clinical response observed in each patient.
Many studies have evaluated the use of several other drugs such as fluoxymesterone, hydrazine sulfate, pentoxifylline, cyproheptadine, dronabinol, eicosapentaenoic acid, and etanercept for treating cancer cachexia, but showed little benefit. Cyproheptadine, the anti-serotonergic drug, was found to be a good appetite stimulant in patients having carcinoid syndrome, perhaps because it counteracts the effects of the serotonin secreted by these patients.
Although eicosapentaenoic acid has been found to improve body composition, appetite, and survival in some trials, these findings were not supported during subsequent phase III trials. Several other drugs such as thalidomide, branched-chain amino acids, oxandrolone, metoclopramide, insulin, and adenosine triphosphate were also evaluated for the management of cancer cachexia. Cytokine inhibitors are the current focus of interest as they may inhibit protein wasting and increase protein synthesis by reversing the cytokine-mediated signals from the cells responsible for cachexia.