National Cancer Institute
Last Modified: August 10, 2002
Inability to maintain nutritional status is a particularly common problem forpersons with cancer. The disease process and its treatment can lead to severeprotein-calorie malnutrition, which is the single most common paraneoplasticsyndrome or secondary diagnosis in the cancer patient. It is a major cause ofmorbidity and mortality. Protein-calorie malnutrition exists when the intakeof macronutrients is inadequate to meet metabolic requirements. Progressivewasting, weakness, debilitation, compromised immune function, potential therapyintolerance, and ultimately death may result.
Anorexia, the loss of appetite or desire to eat, is the most common symptom inpeople with cancer that may occur early in the disease process or later as thetumor grows and metastasizes. 1 Anorexia is present in 15% to 25% of allcancer patients at the time of diagnosis and is almost universal in patientswith widely metastatic disease. 2 3 Anorexia is the most common cause ofdecreased nutrient intake triggering malnutrition and progressive inanition(progressive deterioration with muscle wasting and body compositional change)in malignancy.
Cachexia is a clinical wasting syndrome evidenced by weakness and a marked andprogressive loss of body weight, fat, and muscle. 4 Anorexia and cachexiafrequently occur together, but cachexia may occur in individuals who areingesting adequate calories and protein but experience malabsorption ofnutrients. It has been estimated that one half of all people with cancerexperience cachexia, two thirds while in a terminal phase of the disease. 5 In addition, investigators have found no association between cachexia and tumorsize, type, or extent. 6 It has been observed that cancer cachexia differsfrom simple starvation. 7 Individuals adapt to starvation by decreasing theirbasal metabolic rate, whereas in cancer patients, the basal metabolic rate isnot adaptive and may be increased, decreased, or normal. 8 Although the exactmechanisms causing cancer cachexia are unknown, several theories regarding itspathogenesis point to a complex mix of tumor, host, and treatment variables,which make this syndrome difficult to study.
The prognostic impact of weight loss and malnutrition has been documented sincethe 1930s 9 in benign disease and later in malignant disease. 10 11 12 13 It hasbeen estimated that up to 20% of people with cancer may die of the effects ofcancer-included or treatment-related inanition. Additionally, the impact ofmalnutrition on health care costs is substantial. 14 15
Many nutritional problems in the person with cancer stem from a local tumoreffect. 1 Enlarging tumors in the gastrointestinal tract, for example, cancause obstruction, nausea and vomiting, impaired digestion, delayed transit,and malabsorption. Ovarian and genitourinary cancers may be associated withascites leading to early satiety, progressive protein malnutrition (especiallywith fluid loss at surgery or paracentesis), and fluid and electrolyteimbalances. Pain related to tumor bulk or location may be associated withsevere anorexia and decreased oral intake. Central nervous system tumors thatcause confusion or somnolence may affect nutritional status because lack ofattention may lead to decreased intake.
In addition to local tumor effects (from either the tumor itself or thepatient's response to the tumor), nutritional problems can also stem frommetabolic alterations. 2 Marked alteration in normal metabolism ofcarbohydrate, protein, and lipid can occur. Tumor cells may derive significantenergy from metabolism of glucose to lactate (Cori cycle) rather than from morecomplete oxidation of carbon dioxide and water (Krebs cycle). 3 Additionally,conversion of lactate to glucose for gluconeogenesis by the liver consumes sixATP molecules per lactate-glucose cycle, producing energy-inefficient cycling. Tumor cells have an increased requirement for glucose as an energy source,either through altered enzymatic activity or due to relative hypoxia induced bypoor tumor vascularization. Differences in the contribution of Cori cycleactivity have been seen in patients who lose weight and in those with stableweight. 2 Inhibition of phosphoenolpyruvate carboxykinase by hydrazinesulfate may decrease excess Cori cycle activity and improve glucose tolerancein cancer patients, but weight loss may not be reversed. 2 Altered proteinmetabolism in patients with cancer may stem from increased uptake of aminoacids by the tumor cells compared with that of normal cells, decreased proteinsynthesis, increased protein degradation, and protein loss through fistulas orby gastrointestinal losses. In addition, decreased intake secondary toanorexia, when need is increased or normal, is often the basis of negativenitrogen balance. Altered lipid metabolism can occur as a result ofmobilization and the use of fatty acids as an additional energy source when theglucose supply of the body is exhausted by the tumor. 4 A decrease in fatmobilization has also been observed. 5 6
Mediators of primary cachexia (i.e., cachexia without a mechanical or functionetiology) can include substances with hormone-like characteristics or productsof host tissues that influence metabolism indirectly. The latter include anumber of cytokines such as tumor necrosis factor (TNF-alpha), interleukin-6,and gamma-interferon. Additionally, lipid mobilizing factors have also beenimplicated. 2 Lack of enteral stimulation may increase levels of circulatingcytokines.
In addition to alterations in carbohydrate, protein, and lipid metabolism,cancer cells produce peptides, oligonucleotides, and other metabolites that maybe responsible for the genesis of anorexia and cachexia. 2 For example,tumor-produced substances may alter a person's sense of taste, leading to anaversion to meat and a decreased taste sensation. Tumors may cause anorexiathrough a peripheral effect on neuroendocrine cells or neuroreceptors andthrough a direct effect on hypothalamic and other central nervous systempeptidergic and responder cells. Early satiety or a sense of fullness is afrequent symptom in anorectic cancer patients, suggesting the importance ofinhibitory signals from the gastrointestinal tract in limiting their foodintake. Tumors can also produce hormone substances, similar to those seen inparaneoplastic syndromes, which can alter nutrient intake, absorption, andmetabolism. 7
Cancer therapies and their side effects can also greatly contribute toprogressive nutritional deterioration. The therapy may have a direct effect,such as protein and fat malabsorption after a gastrectomy or pancreatectomy, orindirect effects, such as increases in metabolic demands caused by infection ora neutropenic febrile reaction (there is an increased caloric need ofapproximately 10% to 13% per degree above 37 degrees Celsius). Nutritionalproblems can be induced by each general type of antineoplastic therapy. 1 2 The nutritional literature has defined severe malnutrition in two ways:functionally (increased risk of morbidity and/or mortality) and by degree ofweight loss (greater than 2% per week, 5% per month, 7.5% per 3 months, and 10%per 6 months). 3 In the cooperative group format, nutrition toxicity does notgenerally take into account baseline deficit and includes degrees of weightloss that are much greater than the above criteria. Grading (withoutconsideration of time course) is as follows: grade 0 = less than 5.0% loss,grade 1 = 5.0%-9.9%, grade 2 = 10.0%-19.9%, grade 3 = greater than 20.0%. Grade 4 (life-threatening) is not specifically defined. Attention to weightloss at an earlier time point is required to successfully prevent deteriorationof weight, body composition, and performance status.
Head and neck surgery may directly cause difficulty in chewing and swallowingor may be associated with substantial psychosocial stresses related to thedegree of surgical resection. Esophageal surgery may cause gastric stasis andfat malabsorption secondary to vagal sectioning. Fat and proteinmalabsorption, dumping syndrome with reactive hypoglycemia, and early satietymay occur following gastric surgery. Pancreatic surgery may also cause proteinand fat malabsorption, as well as vitamin and mineral deficiencies, anddiabetes mellitus. Small bowel and colon surgery may cause protein and fatmalabsorption, vitamin and mineral deficiencies, diarrhea, and excessive fluidand electrolyte losses. Surgery involving the urinary tract can lead toacid-base imbalances and electrolyte abnormalities. Additionally,complications of surgery with nutritional implications may include infection,fistulae (internal or enterocutaneous), and short-bowel syndrome. Patients mayactively decrease their oral intake after a diverting or end colostomy todecrease the ostomy output. This should be addressed in any patient with amarked decrease in oral intake after such surgery.
Chemotherapy can cause anorexia, nausea and/or vomiting, diarrhea orconstipation, stomatitis/mucositis, taste alterations or aversions, andinfectious complications. Symptoms that have an impact on nutrition and thatlast longer than 2 weeks are especially significant. The frequency andseverity of these side effects depend on the class of drug, the dose, the drugcombination, and whether the chemotherapy is part of a combined modalityprogram. Nutritional status may be strongly affected with prolonged treatmentof febrile neutropenia where metabolic needs may increase 25% with atemperature of 39 degrees Celsius.
Radiation therapy is associated with both acute and late sequelae that affectnutritional status. Irradiation of the head and neck area can induce or beassociated with anorexia, taste alterations or aversions, dry mouth, mucositis,gingivitis, dysphagia, trismus, dental caries, and abscess formation. Thoracicirradiation may be associated with esophagitis (radiation-induced esophagealmucositis, candidiasis, or viral infections), dysphagia, esophageal reflux, andnausea and vomiting. Diarrhea, nausea and vomiting, enteritis, proctitis, orfistula formation are possible side effects caused by abdominal or pelvicirradiation. Use of a pelvic sling, tissue expander in the pelvis, or othermethods for removing the small bowel from a pelvic irradiation field may beincluded as part of surgery to decrease these complications. Radiation therapymay also be associated with fatigue, which may result in decreased appetite andmotivation to eat. Late sequelae include strictures, chronic radiationenteritis, malabsorption, or gastrointestinal obstruction.
Immunotherapy (e.g., biologic response modifiers) may be associated with fever,fatigue, and weakness, which can lead to decreased appetite and increased needfor protein and calories. Again, febrile reactions are associated with anapproximate 10% increase in metabolic requirements per degree above 37 degreesCelsius.
Dining is a major focus of social activity. Anorexia and food aversionscontribute to social isolation when people cannot participate in communalactivities associated with eating. Multiple psychological and social factorscan affect a person's desire and willingness to eat. The stress of coping withthe cancer diagnosis and its treatment can have a major role. Depression,anxiety, anger, and fear are common emotions experienced by persons with cancerand can contribute to anorexia. A sense of loss of control or helplessness mayalso have a role in nutritional intake. Refusing to eat despite strongrecommendations or pleading by family members, friends, or health professionalsmay be one way in which a patient (who may feel no option to refuseantineoplastic therapy) feels able to exercise some control in life. Learnedfood aversions may also contribute to decreased oral intake, nausea, and/orvomiting. 1 Individuals who have experienced unpleasant symptoms after eatinga specific food may begin to avoid this food or food group.
Factors such as living alone, inability to cook or prepare meals, or even towalk to the kitchen as a result of physical limitations can contribute toeating disorders. A thorough evaluation of the home situation by a socialworker or visiting nurse may identify easily correctable factors thatcontribute to poor eating habits.
Establishing the cancer diagnosis and initiating treatment often require thepatient to spend large amounts of time away from normal routines, includingmeals. Cultural food preferences may not be accessible in treatment settingsor may not be well tolerated because of treatment side effects. A person whoenjoys hot, spicy food and has esophagitis may dislike the taste of bland foodand eat very little. Taste alterations can psychologically affect a person'sappetite and desire for food.
Unfortunately, lack of adequate nutritional intake leads to progressivenutritional deterioration, representing to the patient and family, progressionof the cancer process. The wasting is a constant reminder to the patient,family, and health care team of the cancer diagnosis and expected poorprognosis. This can significantly influence quality of life, socialinteraction, and outlook. Additionally, with progressive wasting, and itsassociated fatigue, the person generally decreases social interaction. Becauseof the role food and eating have in society, this can serve as a significantisolation factor for a person with cancer.
Studies have reported a positive impact of exercise (e.g., walking or mildaerobic) on the sense of well-being, nausea and vomiting, and nutritionalintake. 2 Patients forced to rely on artificial feeding methods (includingforced oral feeding as well as enteral or parenteral feeding) can experiencedepression, body image changes, and stress related to problems with feedingtubes and equipment. 3 Problems related to nutrition have been identified bycancer patients as the most important factor in affecting their sense ofwell-being, more important than sexuality and continued employment. 4
The history and physical examination are the most important components ofassessment of nutritional status. This should include weight history (current,usual, and ideal); assessment of oral intake changes (type and duration);symptoms impacting on nutrition (including anorexia, nausea and vomiting,diarrhea, constipation, stomatitis/mucositis, dry mouth, taste/olfactoryabnormalities, and pain); medications that may affect intake or metabolicrequirements; other medical conditions that may affect nutritional intake ornutrition intervention options; and performance status evaluation. The personwith cancer should be asked about changes in intake compared with what isnormal for them and the duration of the change if present. Physicalexamination entails a general assessment of physical condition, includingevidence of weight loss, loss of subcutaneous fat, muscle wasting, presence ofsacral or tibial edema, or ascites. Standardized staging criteria for degreeof nutritional deficit or risk have been developed and validated. 1 2 Knownas the Subjective Global Assessment (SGA) of nutritional status, thisevaluation tool has been validated in a number of patient populations includingsurgical, human immunodeficiency virus (HIV), and acquired immunodeficiencysyndrome (AIDS) populations. 2 3 With appropriate training, the method issensitive, specific, and has little interobserver variability. A modificationspecifically developed for oncology patients is currently being piloted.
Obtaining a quantitative as well as qualitative dietary history can be helpfulin dietary assessment, especially as a means of demonstrating to the personwith cancer and his or her family or caregiver, that changes can be made toincrease calorie, protein, and micronutrient intake. Useful data also includespecific likes, dislikes, and intolerances of the person with cancer. Thelatter may help to determine the need for specific supplemental enzymes(lactase, other disaccharidases, or pancreatic enzymes).
Anthropometric measurements such as skin fold thickness and midarm musclecircumference are not useful in clinical situations. However, clinicalpalpation of the tricep muscle can often provide an excellent estimate ofnutrition, since extensors tend to lose muscle faster than flexors. 4 Thismethod of nutritional assessment is limited by both the technique andinterobserver variability. Laboratory evaluations that may contribute tonutritional evaluation or appropriate nutritional intervention includeassessment of visceral protein status (serum transferrin or albumin), renal andliver function, pancreatic endocrine function (glucose), serum electrolytes andminerals (calcium, magnesium, and phosphorus), and hematologic evaluation(total lymphocyte count and red cell indices). Although not routinely used,delayed cutaneous hypersensitivity testing (skin test antigens) may be helpfulto gauge systemic immune function.
Determination of nitrogen balance by 24-hour urinary urea nitrogen (UUN) ishelpful in nutritional intervention regimens, particularly in the use ofenteral or parenteral nutrition. The aim of nutritional intervention is tominimize the degree of negative nitrogen balance (i.e., excessive loss of bodyprotein not compensated by adequate nutritional intake). Nitrogen balance isdefined as nitrogen intake (in grams) minus nitrogen output (in grams) and canbe estimated from (protein intake/6.25) - (UUN+4). If nitrogen intake is lessthan output, the patient is considered to be in negative nitrogen balance, witha net loss of body protein. This contributes to progressive muscle wasting,fatigue, and immune compromise.
Options for supportive nutritional care of the person with cancer aredetermined by one or more of the following:
It is believed that maintenance of body composition and adequate nutritionalstatus can help people with cancer feel and look better and can maintain orimprove performance status and daily functional status. It may also help themtolerate therapy. 1 The type of nutritional intervention used will depend onthe basis of the nutritional risk or deficit. Problems caused by local tumoreffects may subside when the tumor responds to therapy. Those nutritionalimpact symptoms related to side effects of therapy must be proactivelyaddressed to ensure adequate symptom control measures. (Refer to the PDQsummaries on Constipation, Impaction, and Bowel Obstruction; Pain; Nausea andVomiting; and Oral Complications for more information.)
A major cause of anorexia in patients with cancer is food odor. Patientssuffering from anorexia should not be in a room where the odors of foodpreparation can be detected. Foods with reduced odors are preferable forpatients with cancer. This explains why cancer patients will often eat best atbreakfast, since many breakfast foods have little odor.
Suggestions for helping people with cancer manage taste changes include thefollowing:
Suggestions for prevention of conditioned taste aversions include thefollowing:
Suggestions for lessening or alleviating either dry mouth or dysphagia includethe following:
Suggestions for stomatitis (refer to the PDQ summary on Oral Complicationsfor more information):
No matter what the nutritional deficit, the person with cancer should beencouraged to maintain a positive attitude toward treating the cause andassuring adequate intake of protein and calories. Calculating individualizedcalorie and protein requirements and explaining to the person with cancer(and/or family or caregiver) will allow specific and realistic goals. Theactual amount of protein and calories needed by each cancer patient will varydepending on the person's baseline and current nutritional status, particularnutritional deficits, and individual factors.
The protein requirement for non-weight losing individuals is approximately 0.5grams per pound of ideal body weight. For the person who has lost weight, isfebrile, or is on medications that increase protein requirements, such ascorticosteroids, it is important to aim for approximately 0.7 grams per pound. Ideal body weight (IBW) is calculated as follows:
In terms of caloric needs, the following formulas can be used:
Additional calories and increased protein intake may be required for specificpeople and situations. An oncology nutritionist (dietitian, diet technician,nurse, or physician with specialized education or training in nutrition) canoffer guidance in determining the appropriate macronutrient (calories andprotein) and micronutrient (vitamins, electrolytes, minerals) needs and optionsfor nutritional intervention.
An algorithm of nutritional options is available 1 to address nutritionproactively and to prevent or treat malnutrition and its complications.
General indications for enteral nutrition (gastric and duodenal/jejunal, withsite dependent on the intake gastrointestinal impediment) include thefollowing:
General contraindications to enteral nutrition include the following:
General indications for parenteral nutrition (complete or supplemental) includethe following:
General contraindications to parenteral nutrition include the following:
Although there remains continued controversy concerning the ultimate benefit ofnutritional support, 2 it is believed that a properly nourished cancer patientis better able to tolerate both the cancer therapy and its complications. 3 4 The delivery method chosen for nutritional support should be based on theindividual's physiologic requirements, degree of nutritional debilitation,disease process, estimated duration for the need of support, and the resourcesavailable. If the gastrointestinal tract is functioning and not adverselyaffected by the cancer treatment, enteral support is the route of choice,especially when dealing with issues of system immune function. Options forplacement of enteral feeding tubes include non-surgical (via nasal route) aswell as endoscopic, radiologic, laparoscopic, and open surgical placement. Practical issues of tube options and formulations have been reviewed. 5 6
Nutritional Support, Pharmacological Approaches 7
Pharmacologic intervention to increase oral nutritional intake can range frompain management to treatment of constipation or diarrhea, the use of gastricprokinetic agents, and the use of specific orexigenic agents (appetitestimulants). 8 Megestrol acetate (at a recommended dose of 800 mg/day) hasshown success. 9 10 Corticosteroid use in situations other than terminal careis generally not indicated because of exacerbation of progressive musclewasting. Dronabinol as an appetite stimulant has been used primarily in AIDScachexia, but has been suggested for cancer patients, with a dose of 2.5 mg/dayto 5 mg/day.
Hydrazine sulfate has been studied in three multicenter, randomized, phase IIItrials sponsored by the National Cancer Institute, however no clinical benefitswere found. These trials included 600 patients diagnosed with advanced lungcancer and advanced colon cancer. 11 12 13 The end points in these studiesincluded survival, weight gain, nutritional parameters and quality of life. The results of these three studies were negative, with no benefit seen. In thetwo studies of advanced lung cancer patients, the addition of hydrazine sulfateto a standard chemotherapy regimen resulted in somewhat worse quality of life,with no effect on weight gain or loss and a suggestion of decreased time todisease progression and survival when compared with placebo. 11 12 In thetrial evaluating hydrazine sulfate in metastatic colon cancer, the survivaltime for patients receiving the hydrazine was decreased compared with patientsreceiving placebo. 13 Compared with patients receiving placebo, patientsreceiving hydrazine sulfate demonstrated a more rapid deterioration ofperformance scores and quality of life indices, and also experienced more rapidweight loss. The incidence of severe and life threatening treatment-relatedadverse effects, particularly sensory and motor neuropathies were significantlygreater among patients who received hydrazine sulfate.
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).