Costs and Benefits of Nutrition Support in Cancer

Patients with advanced cancer or AIDS are frequently bothered by anorexia, decreased food intake, fatigue, weight loss, muscle wasting, and a decline in functional status. Nutritional support may afford these patients a better, although not longer life. Available interventions include nutrition counseling, homemade or commercial food supplements, appetite stimulants, enteral nutrition, and parenteral nutrition. Conservative cost estimates for these interventions range from $52/month for homemade supplements to $8,400/month for home parenteral nutrition. Clinicians need to be familiar with the benefits, risks, and costs of these therapies in order to suggest appropriate options.

Introduction

Anorexia and weight loss are very common in patients with cancer [1-3]. As an extension to a previously reported study [4], we analyzed the prevalence of decreased appetite, decreased food intake, and weight loss in 644 consecutive mostly ambulatory cancer patients at our outpatient cancer care center in Long Beach, California. We also determined whether patients were underweight, overweight, or within their calculated body weight range, utilizing standard tables as previously published [4]. Patient characteristics are shown in Table 1 and the results of the study are outlined in Table 2.

More than half of the patients had decreased appetite or food intake, about half were underweight, and three quarters had some degree of weight loss. More than a third of patients had weight loss of 10% or more from their pre-illness usual body weight. These findings were true for patients at all stages of disease, and overall, 59% of patients had weight loss of more than 5%.

Anorexia and weight loss is also common in AIDS patients [5-8]. In these patients, weight loss is more prominent during periods of intercurrent secondary infections [9,10].

Clinical Significance and Mechanisms

Significant weight loss is associated with a poorer prognosis in both cancer and AIDS patients [11,12]. The loss of weight is almost always associated with anorexia and decline in caloric intake, with a reduced frequency and amount of food intake. The cause of anorexia and weight loss may be related to the action of various cytokines, such as tumor necrosis factor, gamma interferon, and interleukins 1 and 6, which have effects both on the central nervous system and peripheral sites, such as liver, adipose tissue, and muscle [13,14].

From a quality of life perspective, the clinical significance of anorexia in cancer and AIDS patients is that it is associated with physical discomfort and a decline in functional status. Patients complain of profound lack of appetite, nausea, fatigue, changes in body image with progressive generalized wasting, and ongoing decline in their ability to carry on their usual daily activities. In patients with cancer anorexia, we have shown that changes in appetite correlate well with changes in food intake, weight, and quality of life [1]. Utility measures applied to patients whose health state is impaired by anorexia would be helpful in quantitating the importance of this problem.

One approach to measuring nutrition-related concerns and the importance of these concerns to patients with cancer or AIDS is that of Cella et al through an anorexia/cachexia subscale added to the Functional Assessment of Cancer Therapy (FACT) Quality of Life scale [15]. To better determine the significance of nutrition-related problems to patients, a last item asks "how much do these additional concerns affect your quality of life? [15]"

As indicated in other articles in these proceedings (eg, those by Jane Weeks and Jeanne Mandeblatt), quality of life measures are not true utility measures. Although the former provide clinically valid and helpful information, the latter would be ideal for quantitating the impact of nutritional interventions on quality-adjusted life-years (QALYs). Since it is generally accepted that nutrition support per se does not prolong survival time of patients with advanced cancer, any favorable impact on QALYs would depend on improvements in the quality of life.

Nutritional Assessment

A brief history should include pre-illness weight, height, rate of weight loss prior to evaluation, estimates of caloric and protein intake, and presence of anorexia, nausea, vomiting, diarrhea, dysphagia, or other specific ingestive, metabolic, or absorptive problems [16]. Ideal body weight can be calculated using standard tables and compared to actual weight [16]. Albumin levels are usually performed as part of routine chemistry panels, and are helpful in defining the severity of undernutrition.

Laboratory parameters specifically designed to study the nutritional status of patients with cancer or AIDS-related anorexia and weight loss are unnecessary, adding expense but little helpful information to the assessment. A commonly ordered laboratory test is prealbumin, which has a short half-life of 24 hours. Although low prealbumin levels will confirm that the patient is undernourished and has poor intake, the clinician ought to question whether it provides any additional information that warrants the expense incurred with the test.

It is our practice to have all patients at risk of malnutrition evaluated by the team dietitian. During the first encounter, the dietitian determines further the patient's nutritional status and needs, and provides the patient with appropriate counseling.

Interventions, Benefits, Risks, and Costs

Counseling: The benefits of initial and follow-up evaluations and counseling by a registered dietitian, preferably in the context of a team approach, can be enormous, although difficult to quantify [17]. The main benefits relate to patient satisfaction, nutrition improvement or maintenance, compliance with team or institutional management protocols and guidelines, and a judicious use of risky and expensive treatments. The costs of nutritional counseling are modest when compared to other interventions. (Table 3)

Food Supplements: Liquid concentrated food supplements provide high concentrations of calories and proteins as well as low-volume nutrients, and are reviewed elsewhere [17]. Instant Breakfast and milk provide an inexpensive and usually well-tolerated alternative. Commercial products may be more convenient and better tolerated in those patients with lactose intolerance. Dietitians will help patients select products on the basis of tolerance and palatability. These products are particularly helpful when patients cannot maintain an adequate intake through a regular diet, but are able to swallow and have a relatively intact gastrointestinal tract.

Appetite Stimulants: Several drugs have been tested to see if they will stimulate the appetite of patients with AIDS or cancer and anorexia [8,13,18]. Two drugs (megestrol acetate [Megace] and dronabinol [Marinol]) have been approved by the Food and Drug Administration recently for use in patients with AIDS and weight loss. In addition, corticosteroids have been used in cancer patients with end-stage disease for short-term (3 to 4 weeks) effects on appetite and well-being. Anabolic steroids are also often utilized for this purpose, especially in AIDS patients, although proof of their efficacy is lacking.

Megestrol Acetate: This orally active progesterone hormone derivative is available in the form of an oral suspension and was recently approved for use in patients with AIDS-related weight loss. In these patients, two randomized placebo-controlled clinical trials indicate that megestrol acetate can stimulate appetite, food intake, and weight gain with associated patient-reported improvement in an overall sense of well-being and quality of life parameters [19,20]. Maximum weight change is seen in 2 to 6 weeks in about one quarter of patients, but it is not achieved until after 10 weeks of therapy in more than one third of patients [19]. The effects on appetite and weight are dose-related and sustained as long as the medication is continued. Four previously published randomized double-blind, placebo-controlled trials in patients with advanced cancer, anorexia, and weight loss, demonstrated substantial appetite enhancement in patients receiving megestrol acetate [21-24].

The benefits of megestrol acetate are related mainly to a favorable symptomatic effect that results in improved appetite, food intake, sense of well-being, and quality of life parameters. This hormone derivative is well-tolerated and side effects are infrequent and probably dose dependent. Side effects reported include impotence, vaginal spotting, and deep vein thrombosis.

In the largest AIDS trial, impotence was a reported side effect in 3% of placebo patients and in 4%, 6%, and 14% of megestrol acetate patients receiving 100 mg/d, 400 mg/d, and 800 mg/d, respectively. Deep vein thrombosis was reported in one patient out of 232 receiving megestrol acetate. Although thrombotic complications have been infrequent, a trend for a dose-related increase in thromboembolic events has been reported in cancer patients [25]. The weight-gain seen with megestrol acetate is due to increased body mass, and is not due to edema [19,23]. Charges according to drug dose are shown in Table 3.

Dronabinol: This marijuana derivative has been in use as an antiemetic and was recently tested in a randomized double-blind placebo-controlled trial in patients with AIDS-related anorexia and weight loss [26]. Patients receiving dronabinol reported improved appetite and mood compared to placebo. There was no significant effect on body weight. Adverse events consisted of euphoria, somnolence, dizziness, and confusion. No randomized clinical trials have been so far reported in patients with cancer. Charges correlated with dosage are listed in Table 3.

Prednisone: This and other corticosteroids have been used for some time by oncologists as appetite and mood enhancers in patients with end-stage disease and very poor short-term prognosis. Randomized trials in cancer patients have shown a short-lived (usually 4 weeks) period of appetite enhancement, without weight-gain [27-30]. Corticosteroids are generally contraindicated in patients with AIDS because of their immunosuppressive effects, and therefore have not been tried as appetite enhancers in this disease. Side effects of corticosteroids are common and can be serious. They include immune suppression, dysphoria, insomnia, hyperglycemia, muscle weakness, cushingoid features, edema, hypokalemia, and gastrointestinal intolerance. Charges for prednisone are low and are shown in Table 3; however, the true cost of using this drug may be higher than that shown in Table 3 because of the need for laboratory tests to monitor glucose and potassium levels, and expenses related to potential complications.

Other compounds such as cyproheptadine and hydrazine sulfate have been tried and shown to be ineffective in patients with cancer-induced anorexia/cachexia [31-33]. Anabolic steroids are often prescribed in patients with AIDS-related weight loss. However, there are no formal clinical trial data to support their use in cancer or AIDS-related weight loss unless there is endocrinologic evidence of male hypogonadism. This subject is worthy of further study, and the cost of androgenic hormones is generally modest.

Enteral Nutrition

Enteral nutrition via nasogastric, gastrostomy, or jejunostomy tube feedings may be indicated in patients who are unable to swallow or who have obstructions or dysfunctions that prevent them from safely transferring liquid or solid food into the upper gastrointestinal tract. It is important that the decisions about tube feedings be made by the nutrition support team after proper evaluation and counseling of the patient. This will avoid initiating enteral nutrition in instances where a more conservative approach may be successful [34,35]. Gastrostomy tube feedings have been reported to offer an advantage in terms of nutrition parameters, quality of life, and functional status in patients who are receiving combined modality treatments for head and neck cancer, or upper gastrointestinal malignancies [36-38].

Decisions in these patients need to be individualized, however, because many patients will do well if instructed and helped from the onset of therapy by a skilled dietitian. If the reason for tube feedings is anorexia per se, without obstruction, strong consideration should be given first to counseling, food supplements, and appetite enhancers because they can be quite effective, less risky, and certainly much less expensive.

The main serious risk of enteral feeding is aspiration, a complication more likely to occur where there is impaired gastric emptying or tube misplacement, or when the patient is fed in the supine position. Additional side effects include diarrhea or constipation, nausea, vomiting, abdominal cramps, bloating, and distention [35]. The costs of home enteral feeding are presented in Tables 3 and 4. Cancer accounts for the majority of new cases of home enteral nutrition (Figure 1) [39], and it is estimated that the yearly cost for home enteral nutrition nationally is $357 million [39].

Parenteral Nutrition

Parenteral nutrition is indicated in patients who cannot be fed via the gastrointestinal tract. Outside this indication, its use in the setting of advanced cancer or AIDS is controversial. It has recently been reported that cancer patients, however, account for the majority of home parenteral nutrition cases in the United States (Figure 1) [39].

Ethical issues are important when consideration is given to nutritional support in end-stage cancer or AIDS. One must distinguish between hydration therapy, which is obviously less expensive, and total parenteral nutrition. The wishes of the patient and family, as well as the clinical circumstances, must be carefully balanced in order to make appropriate decisions. Parenteral nutrition is clearly not advisable as an adjunct to cancer therapy, and should be used judiciously because of the limited benefits, and high risks and expenses it imposes [40,41]. It is, in fact, unclear whether any additional life or quality of life is gained with parenteral nutrition in patients with advanced cancer.

Risks: Parenteral nutrition is associated with serious risks, including complications of intravenous device placement and maintenance (pneumothorax, venous thromboembolism, hemorrhage, exit site infection, bacteremia, and sepsis), and side effects of intravenous nutrition (electrolyte imbalance, hepatic dysfunction, fluid imbalance) [42]. Parenteral nutrition requires close supervision, catheter care, frequent laboratory tests, and consequently multiple ongoing human resources are required, including physician, pharmacist, and nurse. The costs of home parenteral nutrition are shown in Tables 3 and 4. As shown in Figure 1, cancer accounts for the majority of new cases of home parenteral nutrition, and it is estimated that the yearly cost of home parenteral nutrition is $780 million [39]. The yearly cost for hospital parenteral nutrition is estimated at $6 billion [43].

Conclusions

Figure 2 represents a method for choosing between alternative therapies directed to a common goal (ie, improving health-related quality-adjusted life-years [HR-QALYs]). From a healthcare standpoint, an intervention may be indicated, provided it improves the length of life and/or its quality. A therapy will be beneficial and acceptable if the combination of its effects on HR-QALYs warrants its use and supports the expense it requires [44]. As a point of reference, a cost of $42,000 to $80,300 per life-year has been quoted in patients receiving renal dialysis [45]. When choosing between two or more alternative therapies, it is helpful to determine which therapy offers the most favorable ratio of cost vs quality-adjusted survival. The case of nutrition support in cancer and AIDS offers an opportunity to apply this type of analysis. Since in most instances the length of survival is not affected, quality of life is the one dimension that determines the benefits obtained.

The conclusion to be drawn is that, in order to make rational decisions, the effects of nutrition support interventions on quality of life must be measured and reported; and similarly, the cost of such interventions must be known. The clinician and patient may then choose from available nutrition support maneuvers by evaluating their effects on quality of life, and their costs.

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