Anorexia-Cachexia Syndrome


Background

Anorexia-cachexia syndrome is defined as progressive weight loss associated with malignancy and is characterized by loss of appetite (anorexia), skeletal muscle wasting, and reduced adipose tissue.1,2 Cachexia is considered to be the involuntary loss of more than 10% of the original weight3, often appears concurrently with anorexia, and can be considered a syndrome. Although the exact mechanism of this syndrome remains poorly understood, the pathogenesis is thought to be multifactorial, with cytokines and tumor-related factors playing an important role.4
Primary anorexia-cachexia in cancer is a metabolic syndrome caused directly by the tumor
Secondary anorexia-cachexia represents a combination of factors such as malnutrition caused by impaired oral intake, impaired absorption of nutrients, and loss of proteins through body fluids
Infections may also contribute to anorexia-cachexia syndrome, as does loss of muscle mass due to prolonged inactivity.2 Increased protein catabolism is thought to be a significant element of this syndrome.5 Anorexia-cachexia syndrome is associated with weight loss and malnourishment, as often seen in late-stage disease, and usually associated with poor prognosis and early death.2,6  Nearly 80% of patients with advanced cancer may experience this syndrome, and it may account for up to 20% of deaths.7

Alteration in taste is one of the most common symptoms associated with cancer and chemotherapy treatments and is often a significant contributor to anorexia-cachexia syndrome.  Patients receiving chemotherapy may experience sensations of unpleasant taste (dysgeusia), loss of taste (ageusia), or decreased taste sensation (hypogeusia). Dysgeusia, the most commonly reported change,8 may be due to diffusion of drug into the oral cavity.
Berteretche et al reported that 62% of patients complained of taste disorders associated with chemotherapy treatments9
Rehwaldt et al,10  in a study of 42 patients receiving chemotherapy, found that taste changes most frequently reported by patients were metallic taste (78%), no sense of taste (68%), and bitter taste (57%)10
Comeau et al11 found the most common complaints include a metallic taste, enhanced taste of bitter flavors, and a reduced taste of sweet flavors11

Little is known about the chronic effects of chemotherapy on taste, although the literature suggests that dysgeusia is reversible, with taste sensation returning to normal in the ensuing months.8,10 Taste dysfunction seems to occur with equal frequency between oral and intravenous chemotherapy.

Simple dietary changes as well as the addition of certain spices and flavorings can make food taste better and less offensive. Figure 1 suggests techniques for managing taste change in patients with cancer.
Figure 1. Strategies for Management of Taste Alterations
Eat small, frequent meals and healthy snacks
Use plastic utensils if food tastes metallic
Substitute poultry, fish, eggs, cheese, beans, and other protein sources for red meats
Season foods with tart flavors, such as lemon wedges, citrus fruits, vinegar, and marinades to overpower bad or off tastes (if patient does not have mucositis)
Marinate meats or fish to change the taste
Suck on sugar-free lemon candy, gum, or mints to eliminate metallic or bitter taste
Add spices such as onions, garlic, basil, and sauces to foods
Practice regular mouth care before eating to remove bad taste and refresh the mouth
Eat foods cold or at room temperature
Drink water with foods
Based on information from Rehwaldt et al10 and National Cancer Institute.12

Etiology and Risk Factors

In a 1980 multi-institutional, retrospective review of 3047 clinical protocol cancer patients from the Eastern Cooperative Oncology Group, weight loss of more than 5% of premorbid weight prior to the initiation of chemotherapy was predictive of early mortality. Weight loss was independent of disease stage, tumor histology, and patient performance status in its predictive value. A higher frequency of weight loss was found in patients with solid tumors, such as GI malignancies, compared with those with hematologic malignancies.13

Potential etiologic factors in the development of anorexia-cachexia syndrome include the following1-7:
Alteration in taste or smell
Alteration in gastrointestinal function
Early satiety
Mucositis
Diarrhea
Obstruction
Nausea/vomiting
Psychological abnormalities
Depression
Grief
Anxiety
Pain
Cancer treatment
Radiation therapy
Chemotherapy
Surgery

Assessment

Clinicians have used objective parameters such as body mass index, weight loss, and biochemical changes to assess nutritional status in both healthy individuals and patients with cancer. Subjective global assessment (SGA) assesses nutritional status based on the features of a history (weight change, dietary intake change, GI symptoms that have persisted for greater than 2 weeks, and functional capacity) and physical examination (loss of subcutaneous fat, muscle wasting, ankle/sacral edema, and ascites). Features are combined subjectively into a global assessment in which patients are rated as being well nourished, moderately (or suspected of being) malnourished, or severely malnourished. The patient completes a brief self-assessment and the remainder of the SGA is completed by a health care professional such as a nurse, dietitian, or physician (download pdf of SGA tool). Subjective global assessment has been found to have a high degree of interrater reliability.14-15

Risk factor assessment and nutritional screening are essential for early identification of patients at risk. A complete history should be obtained, including pre-illness and current dietary habits, current disease status, medications, functional status, income level, social and psychological factors, cognitive function, and possible side effects of treatment.

Assessment Tools

Three tools that may be used to screen for malnutrition are as follows1:
Body mass index (BMI)
Serum albumin level
Percentage of weight loss
A useful screening tool in the oncology patient is the Subjective Global Assessment (SGA) of Nutritional Status (download pdf of SGA tool) . This tool estimates the nutritional status based on history (weight, current dietary intake, GI symptoms, functional status, and physical demands) and physical examination (muscle features, fat, and fluid status). The results determine whether the patient is well nourished, has moderate or suspected malnutrition, or has severe malnutrition.15

A listing of patient- and nurse-suggested self-care techniques for adapting to and coping with taste changes is included as an appendix in an article by Rehwaldt et al.10 Offering this self-care list to patients who have experienced or are at risk for treatment- or disease-related taste changes may serve as an intervention assessment tool. The list also provides a checklist for discussion with patients regarding techniques that do or do not work for each individual patient.

Pharmacologic and Nonpharmacologic Treatment and Supportive Care

Current pharmacologic and nonpharmacologic treatment (Figure 2) is directed toward reversing the syndrome and improving quality of life. Primary pharmacologic management of cancer cachexia has included the administration of orexigenic (appetite stimulants), anticatabolic (antimetabolic and anticytokine), and anabolic agents (primarily hormonal).5  Although many of these agents have been used in the treatment of anorexia-cachexia, benefits are usually of short-term duration, with no influence on lean body mass or survival.17,18 A study by Navari and colleagues19 found that
A combination of olanzapine, a drug used to treat schizophrenia and other psychoses, and megestrol acetate was effective in treating cancer-related anorexia in a group of 80 patients
20 of the 39 patients randomized to receive olanzapine + megestrol acetate had significant improvements in weight gain, appetite, nausea, and quality of life measures
Of the 37 patients who received megestrol acetate alone, 21 experienced weight gain, but there was no significant change in appetite, nausea, or quality of life

A larger, randomized trial is planned.19

Figure 2. Pharmacologic and Nonpharmacologic Treatment to Increase Appetite2,4,5,16,17
Pharmacologic measures
Appetite stimulants: megesterol acetate and medroxyprogesterone
Corticosteroids: dexamethasone or prednisone
Tetrahydrocannabinol: dronabinol
Anabolic agents: oxandrolone
Nonpharmacologic measures
Physical exercise
Relaxation exercises
Dietary counseling

Most patients with anorexia-cachexia syndrome have advanced cancer; therefore, supportive strategies should emphasize a palliative approach. Figure 3 lists strategies for managing weight loss in patients with cancer.
Figure 3. Strategies for Managing Weight Loss in Patients With Cancer
Increase calories and protein by encouraging consumption of foods packed with macronutrients, vitamins, and minerals
Consider using meal replacements either with or between meals
Limit beverages at meals to avoid early satiety; however, to avoid dehydration, ensure that adequate fluids are being consumed between meals
Serve foods at room temperature and encourage good oral hygiene
Schedule meals as you would medicine, encouraging small, frequent meals throughout the day
Consider the need for an appetite stimulant
Be proactive! Preventing weight loss is more effective than promoting weight gain
Based on information from Grande-Cameron and Lynch,2 Palombine.20

It has been suggested that chemotherapy may play a role in the management of cancer-related anorexia-cachexia syndrome. Some clinical trials have demonstrated that based on tumor response, patients may experience improvement in appetite following treatment. Additionally, it has been reported in some studies that the administration of chemotherapy may suggest a trend in improvement in asthenia, thus providing a palliative benefit to patients with metastatic disease who have this syndrome.21

Anecdotal reports of dietary supplements, including amino acids such as leucine and arginine, may support their use, but randomized clinical trials are lacking.2,17,20 One report on the efficacy of omega-3 fatty acids (fish oil) suggests that this does not appear effective at reducing anorexia or cachexia experienced by patients with advanced cancer. Bruera et al22 randomized 60 patients with advanced cancer to receive either fish oil capsules or placebo daily for 2 weeks. At the start of the study and at completion, patients were assessed for appetite, tiredness, nausea, well-being, caloric intake, nutritional status, and function. The average daily dose of fish oil contained 1.8 grams of eicosapentaenoic acid (EPA) and 1.2 grams of docosahexaenoic acid (DHA), 2 of the main active ingredients in fish oil. At the end of the trial, none of the measured symptomatic or nutritional parameters were significantly different between the group receiving fish oil and that receiving placebo.22

Clinical Practice Guidelines

Oncology Nursing Society Putting Evidence Into Practice® (PEP): Anorexia http://ons.org/Research/PEP/media/ons/docs/research/outcomes/anorexia/guidelines.pdf
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology™, Palliative Care http://www.nccn.org/  [Free, registration required]

Patient Resources

Oncology Nursing Society – The Cancer Journey: Anorexia
http://www.thecancerjourney.org/side/se-2   

American Cancer Society. Caring for the Patient with Cancer at Home: Poor Appetite
http://www.cancer.org/treatment/treatmentsandsideeffects/physicalsideeffects/dealingwithsymptomsathome/caring-for-the-patient-with-cancer-at-home-poor-appetite

American Cancer Society. Nutrition for People with Cancer http://www.cancer.org/docroot/MBC/content/MBC_6_2X_When_Things_Arent_Tasting_Right.asp?sitearea=MBC

American Dietetic Association (ADA)
Nutrition During and After Cancer Treatment
http://www.eatright.org/Public/content.aspx?id=4294967443

 
References

Koutkia P, Apovian C, Blackburn G. Nutrition support. In: Berger AM, Portenoy RK, Weissman DE, eds. Principles & Practice of Palliative Care & Supportive Oncology. Philadelphia: Lippincott Williams & Wilkins. 2002:933-955.
Grande-Cameron C, Lynch MP. Cancer cachexia. In: Brown CG, ed. A Guide to Oncology Symptom Management. Pittsburgh PA: Oncology Nursing Society. 2010:65-89.
Dahlin C, Lynch M, Szmuilowicz E, Jackson V. Management of symptoms other than pain. Anesthesiol Clin. 2006;24:39-60.
Inui A. Cancer anorexia-cachexia syndrome: current issues in research and management. CA Cancer J Clin. 2002;52:72-91.
Loprinzi C, Jatoi A. Pharmacologic management of cancer anorexia/cachexia. http://www.utdol.com/patients/content/topic.do?topicKey=~cMk0fpsgNqsAR0. Accessed January 9, 2011.
Garcia J, Polvino W. Effect on body weight and safety of RC-1291, a novel, orally available ghrelin mimetic and growth hormone secretagogue: results of a phase I, randomized, placebo-controlled, multiple-dose study in healthy volunteers. Oncologist. 2007;12:594-600.
Tisdale MJ. Cachexia in cancer patients. Nat Rev Cancer. 2002;2:862-871.
Prommer E.  Taste alterations in cancer. Proc Am Soc Clin Oncol. 22:2003. Abstract 3093. http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=23&abstractID=100505. Accessed January 9, 2011.
Berteretche MV, Dalix AM, d’Ornano AM, et al. Decreased taste sensitivity in cancer patients under chemotherapy. Support Care Cancer. 2004;12:571-576.
Rehwaldt M, Wickham R, Purl S, et al. Self-care strategies to cope with taste changes after chemotherapy [Online Exclusive]. Oncol Nurs Forum. 2009;36:E47-E56. doi: 10.1188/09.ONF.E47-E56.
Comeau TB, Epstein JB, Migas C. Taste and smell dysfunction in patients receiving chemotherapy: a review of current knowledge. Support Care Cancer. 2001;9:575-580.
National Cancer Institute. Nutrition in cancer care. 2009. http://www.nci.nih.gov/cancertopics/pdq/supportivecare/nutrition/HealthProfessional/page1. Accessed January 9, 2011.
Dewys WD, Begg C, Lavin PT, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med. 1980;69:491-497.
Detsky AS, Baker JP, O'Rourke K, et al. Predicting nutrition associated complications for patients undergoing gastrointestinal surgery. J Parenter Enteral Nutr. 1987;11:440-446.
Detsky AS, McLaughlin JR, Baker JP, et al. What is subjective global assessment of nutritional status? J Parenter Enteral Nutr. 1987;11:8-13.
Arensmeyer K. Nursing management of patients with cancer-related anorexia. http://www.oncolink.org/resources/article.cfm?c=16&s=59&ss=224&id=1006. Accessed January 9, 2011.
Adams LA, Shepard N, Caruso RA, et al. Putting evidence into practice: evidence-based interventions to prevent and manage anorexia. Clin J Oncol Nurs. 2009;13:95-102. doi: 10.1188/09.CJON.95-102.
Gordon JN, Green SR, Goggin PM. Cancer cachexia. Q J Med. 2005;98:779-788.
Navari RM, Brenner MC. Treatment of cancer related anorexia with olanzapine and megestrol acetate: a randomized trial. Support Care Cancer. 2009; Epub September 11, 2009. doi: 10.1007/s00520-009-0739-7.
Palombine J. Cancer-related weight loss. Clin J Oncol Nurs. 2006;10:831-832.
Jatoi MD. Pharmacologic therapy for the cancer anorexia/weight loss syndrome: a data-driven, practical approach. Support Oncol. 2006;4:499-502.
Bruera E, Strasser F, Palmer JL, et al. Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double-blind, placebo-controlled study. J Clin Oncol. 2003;21:129-134.

 
Key Definitions

asthenia—lack or loss of strength

body mass index (BMI)—a measure of body fat that is the ratio of the weight of the body in kilograms to the square of its height in meters

cytokines—any of a class of immunoregulatory proteins (as interleukin, tumor necrosis factor, and interferon) that are secreted by cells especially of the immune system

etiologic—causing or contributing to the cause of a disease or condition

frequency—the number of individuals in a single class when objects are classified according to variations in a set of one or more specified attributes; the number of repetitions of a periodic process in a unit of time

protein synthesis—a process in which information is taken from DNA to act as a blueprint for creating a particular protein that is in demand by the body.

satiety—the quality or state of being fed to or beyond capacity; a sense of feeling full

syndrome—a group of signs and symptoms that occur together and characterize a particular abnormality