Anorexia and Cachexia

Diagnostic criteria
Management
Nutrition as it relates to end-of-life care
Suggested reading

Many patients with advanced cancer undergo a wasting syndrome associated with cancer anorexia/cachexia and asthenia. In a study that looked at symptoms in cancer patients being entered on a palliative care service, anorexia/cachexia and asthenia were more common problems than was pain or dyspnea. Patients who exhibit such symptoms generally have a short survival time, respond poorly to cytotoxic agents, and suffer from increased toxicity from these agents.

In addition, cancer anorexia/cachexia is oftentimes associated with weakness, fatigue, and a poor quality of life. This problem not only affects the patient but also frequently has an impact on family members, as the patient is no longer able to participate fully in eating as a social activity.

Diagnostic criteria

Although some authors have tried to define criteria for diagnosing cancer cachexia, in general, it is not difficult to identify affected patients. In North Central Cancer Treatment Group (NCCTG) research trials involving over 2,300 patients, very simple criteria for anorexia/cachexia have been used:

A 5-lb weight loss in the preceding 2 months and/or an estimated daily caloric intake < 20 calories/kg
A desire by the patient to increase his or her appetite and gain weight
The physician’s opinion that weight gain would be beneficial for the patient

Management

Nutritional counseling, as provided by written materials, dietitians, physicians, and/or nurses, has been recommended, although its value has not been well demonstrated. Recommendations typically include eating frequent, small meals (as opposed to large meals), consuming larger quantities of food in the morning than in the evening, and avoiding spicy foods. Patients may do better if they are not exposed to the aroma of cooking. Although the benefits of such nutritional counseling are clearly limited, it does appear reasonable to provide.

Appetite stimulants

Corticosteroids were the first agents to undergo placebo-controlled, double-blind evaluation for possible use in cancer cachexia. The first such trial, conducted in the 1970s by Moertel and colleagues at the Mayo Clinic, demonstrated that corticosteroids can stimulate appetite in patients with advanced, incurable cancer. Several subsequent placebo-controlled trials, using various steroid preparations and doses, have confirmed these results.

Dexamethasone (3-8 mg/d) is a reasonable option for clinical use. Known detriments to corticosteroid use include the well-known toxicities associated with chronic administration, including myopathy, peptic ulcer disease, infection, and adrenal suppression. Many patients with advanced cancer anorexia/cachexia, however, do not survive long enough to suffer from these toxicities.

Progestational agents Several placebo-controlled, double-blind clinical trials have demonstrated that progestational agents, such as megestrol acetate and medroxyprogesterone acetate, can lead to appetite stimulation and weight gain in patients with anorexia/cachexia. These trials also demonstrated that the effect of these drugs is seen in a matter of days and that they also are effective antiemetics.

Although high doses of progestational agents can cause adrenal suppression because of their mild corticosteroid-type activity (a phenomenon not well understood by many clinicians), they do not appear to cause many of the side effects attributable to classic corticosteroids (such as peptic ulcer disease, myopathy, and opportunistic infections). On the other hand, progestational agents increase the risk of thromboembolic phenomena㻡 side effect that is not seen with classic corticosteroids.

A dose-response study with megestrol acetate demonstrated a positive correlation between appetite stimulation and increased megestrol acetate doses, as doses ranged from 160 to 800 mg/d. Nonetheless, given that appetite stimulation has been demonstrated with megestrol acetate doses as low as 240 mg/d, much lower doses are used by many physicians, primarily based on cost considerations.

In the United States, a liquid formulation of megestrol acetate is considerably less expensive than the tablet form, and, milligram for milligram, the liquid preparation is more bioavailable. It is reasonable to start with 400 mg/d of liquid megestrol acetate, titrating this dose upward (maximum, 800 mg/d) or downward based on clinical response or the emergence of side effects.

A randomized, prospective clinical trial comparing the utility of megestrol acetate (800 mg/d) to dexamethasone (0.75 mg qid) demonstrated similar effects of these medications on patients?appetites but different toxicity profiles. While megestrol acetate was associated with a higher incidence of thromboembolic phenomena, dexamethasone was associated with more myopathy, cushingoid body changes, and peptic uclers.

Other agents Various other drugs have been evaluated definitively for the treatment of cancer anorexia/cachexia and have been demonstrated to provide little or no benefit. These drugs include fluoxymesterone, pentoxifylline (Trental), hydrazine sulfate, and cyproheptadine. Of note, however, the antiserotonergic drug cyproheptadine does appear to be a relatively strong appetite stimulant in patients with the carcinoid syndrome, presumably because it directly counteracts the large amounts of serotonin secreted in patients with this syndrome.

A number of other drugs have been evaluated in a pilot fashion for the treatment of cancer anorexia/cachexia. These include dronabinol (Marinol), branched-chain amino acids, metoclopramide, and eicosapentaenoic acid. Hopefully, new information will be available in the near future to shed light on the possible therapeutic roles of these agents.

Enteral/parenteral nutrition

Despite the demonstrated efficacy of corticosteroids and progestational agents in patients with cancer anorexia/cachexia, these drugs do not have a major long-term impact on the vast majority of such patients. Consequently, other treatment approaches, such as enteral or parenteral nutritional methods, have been studied extensively. Several randomized trials failed to demonstrate that these nutritional approaches improve either quantity or quality of life. As a result, experts generally agree that the routine use of parenteral or enteral nutrition cannot be justified in patients with advanced cancer anorexia/cachexia.

There are, however, rare circumstances in which parenteral nutrition may have a role to play in patients with advanced cancer. For example, patients with GI insufficiency due to surgery, radiation therapy, or abdominal carcinomatosis (without impending failure of other organs) may be appropriate candidates for parenteral nutrition.

Prophylactic therapy

Given the positive impact of corticosteroids and progestational agents on cancer anorexia/cachexia and the fact that many patients with advanced cancer die with, and/or of, inanition, the potential prophylactic use of these agents was evaluated. A double-blind trial randomized patients with newly diagnosed extensive-stage small-cell lung cancer to receive megestrol acetate or placebo along with standard chemoradiation. This trial was unable to demonstrate any beneficial effect of megestrol acetate on treatment response, quality of life, or survival.

Nutrition as it relates to end-of-life care

Anorexia and cachexia are clearly major problems in many oncology patients when they approach the final stage of life. As discussed above, appetite stimulants, such as megestrol acetate or corticosteroids, can provide some relief of this problem for some patients for a limited time. What should be done if/when these appetite stimulants do not provide relief? In general, the family members are more distressed in this situation than the patient. Questions commonly arise about giving enteral or parenteral nutrition, or about how the patient can be "forced" to consume more calories. Family members often believe that the patient would feel better, get stronger, and live longer if the patient took in more calories. This leads to the use of enteral tube feedings, TPN, and other heroic efforts by family members to have the patient consume more calories.

In this situation, a small measure of appropriate education of patients and family members can provide substantial clinical relief. That education consists of noting that the intake of more calories does not appear to provide clinical benefit in this situation. It may be helpful to relate that there is an animal tumor model whereby animals with implanted tumors, when randomized to receive parenteral nutrition or not, do worse when they get the parenteral nutrition: they experience faster-growing tumors (ie, the nutrition "feeds the tumors") and shorter survivals. It is also worthwhile to note that patients randomized to receive TPN or appetite stimulants (such as megestrol acetate) do not live any longer than do control patients.

Given this, the families can be assured that they need do no more than "gently encouage" the patient to eat, provide the intake that the patient requests, and know that "force feeding" is not in the patient𠏋 best interests.

Anorexia and Cachexia

Diagnostic criteria

Management

Nutrition as it relates to end-of-life care

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