Management of Anorexia-Cachexia in Late-Stage Lung …Anorexia is the loss of appetite or desire to eat.11,12 In acute events, anorexia usually resolves with resolution of the illness,

Management of Anorexia-Cachexia inLate-Stage Lung Cancer Patients

Catherine Del Ferraro, MSN, Ed, BSN, PHN, RN, CCRP ƒ Marcia Grant, DNSc, RN, FAAN ƒMarianna Koczywas, MD ƒ Laura A. Dorr-Uyemura, RD

Nutritional deficiencies are experienced by most adultswith advanced lung cancer during the course of theirdisease and treatment. Well-nourished individualstolerate cancer treatment with less morbidity, mortality,and increased response to treatment as comparedwith those who are malnourished. Novel anticancertherapies cause many deficits that impact nutritionaland functional status during the treatment process.Nutritional deficits include weight loss, malnutrition,and anorexia-cachexia. Anorexia-cachexia is complex,not well understood and seen in many solid tumorsin late-stage disease. Assessing adequate nutrition isone of the most challenging problems for nurses,their patients, and patient’s families. The purposeof this review was to define and describe canceranorexia-cachexia in late-stage lung cancer, throughcase presentation, and to describe palliative strategiesfor prevention, assessment, and management in thepalliative care setting. Early assessment for nutritionalimbalances must be done regularly with reevaluation forintervention effectiveness and should continuethroughout the illness trajectory. Management ofadverse effects of cancer and cancer-related treatmentis critical to improving quality of life. Palliative careand hospice nurses play a critical role in earlyassessment, education, and prevention to supportnutritional needs for patients and their families.

KEY WORDSanorexia, cachexia, cachexia-anorexia syndrome

In 2012, it is estimated there will be about 226,000new cases of lung cancer (nonYsmall cell lung can-cer [NSCLC] and small cell lung cancer [SCLC] com-

bined), and more than 160,000 estimated related deathswill occur in the United States.1 About 20% of the deathswill be caused by the effects of cancer-related anorexia-cachexia syndrome.2 Cancer anorexia-cachexia is a wast-ing syndrome that occurs in 80% of patients with incurablesolid tumors.3 This syndrome is common in specific cancertypes: gastric, 85%; pancreatic, 83%; nonYsmall cell lung,61%; small cell lung, 57%; prostate, 57%; and colon,54%.4 It involves extreme weight loss and malnutrition. Ac-cording to the data, 60% of patients with lung cancer havealready experienced a significant weight loss at diagno-sis.3,5 In addition, cancer itself may be complicated withmetabolic disorders.6 For example, paraneoplastic syn-dromes (PNPs) are rare metabolic disorders that are the re-sult of remote clinical effects of cancer.7 They are not dueto the physical effects of the cancerous tumors but arecaused by substances produced by the tumors acting ontissues in the body.7

Nutritional screening and assessment are recommendedat initial diagnosis, before cancer treatment begins, andshould continue throughout care.5 Agreement exists amongclinicians that cachexia related to cancer occurs inmost pa-tients with advanced lung cancer, and cancer anorexia, theloss of appetite, is a common symptomof cachexia.5 Assess-ing adequate nutrition is one of the most challenging prob-lems for nurses and the interdisciplinary palliative careteam. The purpose of this review was to describe cancer-related anorexia-cachexia in late-stage lung cancer, througha case presentation, and describe current and evolving strat-egies for prevention, assessment, and management. Man-agement strategies presented apply to other cancers andnoncancer illnesses in which effective treatment manage-ment for anorexia-cachexia is required.

CASE PRESENTATION

Mrs A.C. is a 72-year-old elderly Latina woman, who isnewly diagnosed with stage IV NSCLC with metastatic

Catherine Del Ferraro, MSN, Ed, BSN, PHN, RN, CCRP, is Senior Re-search Specialist, Department of Population Sciences, Division of Nurs-ing Research and Education, City of Hope, Duarte, CA.

Marcia Grant, DNSc, RN, FAAN, is Director and Professor, Depart-ment of Population Sciences, Division of Nursing Research and Educa-tion, City of Hope, Duarte, CA.

Marianna Koczywas, MD, is Clinical Professor, Medical Oncology andTherapeutics Research, City of Hope, Duarte, CA.

Laura A. Dorr-Uyemura, RD, is Director, Clinical Nutrition Services,City of Hope, Duarte, CA.

Address correspondence to Catherine Del Ferraro, MSN, Ed, BSN, PHN,RN, CCRP, Division of Nursing Research and Education, City of Hope,1500 E Duarte Rd, Population Science Bldg #173, Room 169, Duarte, CA91010 ([email protected]).

The authors have no conflict of interest to disclose.

This work is supported by a grant from the National Cancer Institute(PO1 CA 136396YPalliative Care for Quality of Life and Symptom Con-cerns in Lung Cancer; B. Ferrell, principal investigator).

DOI: 10.1097/NJH.0b013e31825f3470

Journal of Hospice & Palliative Nursing www.jhpn.com 397

Symptom Management Series

disease to the brain and liver. She initially presentedwhen undergoing preoperative workup for bladder re-construction 1 month ago. Chest x-ray and computed ax-ial tomography scan revealed a 4-cm left upper lobe lungmass. Bronchoscopy with biopsy demonstrated atypicalcells highly suggestive of bronchogenic carcinoma. Sheunderwent a left upper lobectomy with lymph node dis-section. Pathology confirmed a 4-cm poorly differen-tiated adenocarcinoma with clear margins and positivelymph nodes, consistent with adenocarcinoma. She wasreferred to medical oncology for evaluation and an opin-ion of further treatment and care.

A comprehensive physical evaluation of the patientwas done. Mrs A.C. is a thin, elderly bilingual female inno acute distress, alert, and oriented times three. She is5¶4µ tall, weighs 115 lb, with a body mass index (BMI) of19.7 kg/m2. Her vital signs and oxygen saturation arewithin normal limits, and Karnofsky Performance Scale(KPS) score is 70. Her comorbidities include osteoporosis,gastroesophageal reflux disease, and urinary incontinence.She is also status-post two bladder resuspension surgeries.Her current medications are risedronate sodium (Actonel)and lansoprazole (Prevacid). Her family cancer history in-cludes a brother who died at age 80 years of lung cancer,with a heavy smoking history. Her social history revealsthat she is divorced, self-employed, college educated,and a lifetime nonsmoker. She has three adult children.Mrs A.C. lives at her younger son’s home, and he is hercaregiver. She is Catholic and attends church regularly.

A complete blood count and comprehensive meta-bolic panel are normal. Her current complaints are mod-erate back pain, mild hoarse voice, mild hand tremors,moderate continual urinary incontinence, mild constipa-tion, mild dyspnea on exertion, 3-lb weight loss withinthe last month, and mild fatigue.

After discussion of diagnosis, prognosis, treatment op-tions, and goals of care with Mrs A.C. and her family, sheagreed to initiate palliative adjuvant therapy of oral erlo-tinib and whole-brain radiation. Before initiation of treat-ment, the medical oncologist ordered a comprehensivenutritional screening and assessment based on Mrs A.C.’scomplaints and examination noted above. The palliativecare nurse conducted a comprehensive nutritional screen-ing and assessment, assessing subjective and objectiveinformation. The Functional Assessment of Anorexia/Cachexia Treatment (FAACT) tool version 4 (Figure 1) wasutilized to further assess concerns in Mrs A.C.’s appetite.The medical oncologist was notified, and the findings werereviewed with Mrs A.C. and her son.

A treatment plan was formulated with a multimodal ap-proach consistent with the patient and family goals of care.Appropriate pharmacologic interventions were prescribedby the medical oncologist to stimulate appetite (megestrolacetate), control pain (oxycodone with acetaminophen),

and constipation (docusate sodium and sennosides). Non-pharmacologic interventions included referrals to the dieti-tian for nutritional counseling and education; pulmonaryrehabilitation to assess pulmonary function; physical ther-apy to increase strength, endurance, and mobility; occupa-tional therapy to address energy conservation needs forself-care; palliative care medicine for pain management;and radiation oncology for treatment evaluation. Before ad-juvant treatment began, reevaluation of the effectiveness ofinterventions was scheduled in 1 week. Reevaluationnoted a 1-lb increase in weight. Reports by the patientand family included an increased appetite and resolvedpain. She continued to have mild constipation and ad-mitted to ‘‘forgetting’’ to take her stool softener. She alsostated that food was once again appetizing to eat espe-cially foods she was culturally accustomed to cookingfor lent. Treatment was initiated without delay.

CLINICAL CHARACTERISTICS OFANOREXIA-CACHEXIA

Cancer malnutrition has been described as a state of nu-trition in which a deficiency or excess (or imbalance) ofenergy, protein, and other nutrients causes measurableadverse effects on tissue/body form, function, and clini-cal outcome.8 Cancer- related anorexia and cancer-relatedcachexia are distinct syndromes but are often intertwinedin progressive disease.9 Cancer cachexia is unique but dif-ficult to distinguish from other causes of weight or muscleloss such as malnutrition related to cancer anorexia ormalabsorption related to impaired gastrointestinal func-tion.6 Therefore, because they are so closely related, de-finitions of cancer-related anorexia and cachexia have

FIGURE 1. Functional Assessment of Anorexia/Cachexia Treatment(FAACT) tool (http://facit.org).

398 www.jhpn.com Volume 14 & Number 6 & August 2012


been combined and referred to as the ‘‘anorexia- cachexiasyndrome.’’6,10

Anorexia is the loss of appetite or desire to eat.11,12 Inacute events, anorexia usually resolves with resolution ofthe illness, and any weight lost may be replaced with nu-tritional supplements or increased intake.3,5 In lung can-cer patients, anorexia may not be recognized and lead toinsufficient caloric intake and protein-calorie malnutri-tion. Weight loss seen in this starvation phenomenonusually involves loss of fat, rather than muscle tissue.3

The characteristics of anorexia are common amongmany patients with serious illnesses such as lung cancer,acquired immune deficiency syndrome, and other chronicdiseases.3,5 Anorexia is the most common cause of malnu-trition in lung cancer patients and is a symptom that is as-sociated with cachexia.5

Agreement exists that cachexia is a complex syn-drome and not well understood.3,6,8 Cachexia has beenrecognized as a frequent problem in lung cancer patientsand represents an unmet need.6 Cachexia is a multifac-torial syndrome and may or may not be associated withanorexia, along with significant weight loss, loss of mus-cle tissue as well as adipose tissue, and generalized weak-ness.6,13 It is often complicated by other food intakeproblems such as impaired integrity and function of thegastrointestinal tract from mouth to anus and poorly con-trolled physical and psychosocial symptoms including pain,shortness of breath, depression, or severe fatigue.3,6,13,14

The European Palliative Care Research Collaboration(EPCRC) is currently developing classification systemsfor pain, depression, and cachexia in patients with ad-vanced cancer.6,15 This process has been comprehensiveinvolving expert and public consultations and literaturereviews.6,15 The cachexia guideline expert group identi-fied cancer cachexia as a continuum of three stages ofclinical relevance: precachexia, cachexia, and refractorycachexia.6 It was noted that not all patients would movethrough the entire spectrum.6 The stages of cachexia aredefined on the basis of the patient’s characteristics andcircumstances.6,15 Diagnostic criteria for end-stage ca-chexia have been defined by the EPCRC (Figure 2).6,16

In 2010, the cachexia guideline development group pub-lished European Clinical Guidelines on the managementof cachexia in advanced cancer patients with a focus onrefractory cachexia.6

Refractory cachexia is characterized by a low perfor-mance status and life expectancy of less than 3 months.6

Refractory cachexia represents a stage where reversal ofweight loss seems no longer possible because of veryadvanced or rapidly progressive cancer unresponsiveto anticancer therapy.6 In this stage, the burden and risksof artificial nutritional support likely outweigh any po-tential benefit, and therapeutic interventions focus on al-leviating the suffering associated with cachexia, such as

symptom control with appetite stimulation and treatmentof nausea or eating-related distress of patients and fam-ilies.6 The diagnostic criteria include variable degrees ofcachexia, cancer disease both procatabolic and not re-sponsive anticancer treatment, low performance score,and less than 3 months’ expected survival.6

Lung cancer itself may be complicated by the PNPs ofcachexia, which are often associated with anorexia.17

Metabolic PNPs such as hypercalcemia or hyponatremiamay also cause anorexia or symptoms such as fatiguethat contribute to anorexia.9 Overall, PNPs are rare,and only 10% to 20% of the patients with cancer expe-rience metabolic disorders of PNPs over the course oftheir illness.18 Paraneoplastic syndromes occur more fre-quently in patients with lung cancer, particularly in SCLC,occurring in 3% to 5% of patients.18 Paraneoplastic syn-dromes are the result of substances (hormones, growthfactors, cytokines, and antibodies) abnormally secretedby the primary tumor and its metastases.19 These sub-stances affect the endocrine, neurologic, hematologic,and musculoskeletal systems of the body.18 The mostcommon and best understood of the PNPs are of the en-docrine system.20 Endocrine PNPs seen in patients withlung cancer include humoral hypercalcemia of malig-nancy, ectopic adrenocorticotropic hormone syndrome(also known as Cushing syndrome), and syndrome of in-appropriate antidiuretic hormone.20

Basic etiologies of the anorexia-cachexia syndrome are(1) decreased food intake, (2) metabolic abnormalities,(3) the actions of proinflammatory cytokines, (4) systemicinflammation, (5) neurohormonal dysregulation, (6) tu-mor by-products, and (7) the catabolic state.21 Some ofthese mechanisms have a mutually reinforcing aspect;for example, anorexia leads to fatigue, fatigue increasesanorexia, anorexia increases fatigue, and so forth.9

ASSESSMENT OF ANOREXIA-CACHEXIA

Perhaps, the most important element of assessment in-volves patient and family goals of care.3,5,6,9,22 Nutri-tional screening and assessment are done before lungcancer treatment begins.5 Specific recommendations

FIGURE 2. European Palliative Care Research criteria for refractorycachexia.6,16



include completing a nutritional screening and assessmentwithin 48 hours of admission or diagnosis of lung cancer,before initiation of cancer therapy, change in therapy, or aweight change of 2% to 5%.6,22,23 A nutritional screeningprofile is the process of assessing characteristics (early sa-tiety, weight loss, weakness, fatigue, impaired immunefunction, skeletal muscle wasting, and poor performancestatus) of malnutrition and risk factors that will predisposea patient to nutritional deficiencies.17 Predisposing risk fac-tors include: weight loss 5% or less in 1 month, 10% or lessin 6 months, inadequate oral intake for 7 days or less,serum albumin 3.5 g/dL, recent surgery, severe infection,recent radiation therapy or aggressive chemotherapy, per-sistent distress lasting more than 2 weeks, pain, nausea,vomiting, dysphagia, diarrhea, mucositis, depression, an-orexia, diminished self-care or lack of caregiver, demen-tia, poverty, and addiction (alcohol and/or dugs).17,22

Currently, there are no clearly accepted diagnostic criteriafor identifying the specific cause of anorexia-cachexiaseen in lung cancer, but anorexia from some etiologiesis treatable, and assessment of the possible presence ofcauses as mentioned above is vital to quality palliativecare.6,9 Early recognition of the etiologies followed bycomprehensive assessments is recognized as imperativein the development of assessment guidelines.5,6,22 Otherareas of assessment include laboratory values, anthropo-metric measures (BMI), and tools to assess functioningand performance and prognosis such as the KPS, andthe use of multidimensional standardized instruments,such as the FAACT tool (Figure 2).6,8,9

MANAGEMENT OFANOREXIA-CACHEXIA

The best way to treat anorexia-cachexia seen in lungcancer is obviously to cure lung cancer; this will normal-ize the metabolic abnormalities induced by the tumorand/or tumor host interactions.6,21,24 If cure cannot beachieved, the next option would be to increase nutri-tional intake by dietary counseling and education andoral nutritional supplements.5,6 Early intervention to tryto prevent malnutrition is easier than trying to reverseit after it occurs.25 Therefore, management is multimodalwith the focus of stabilizing weight, improving comfort,lowering the risk of infection, keeping up strength andenergy, minimizing distress, and improving quality of life(QOL).5,9 As previously stated, management and recom-mendations for anorexia-cachexia seen in lung cancerapply to other advanced cancers and illnesses.

The National Comprehensive Cancer Network (NCCN)has published Guidelines for Supportive and PalliativeCare Symptom Management for anorexia-cachexia(Figure 3).26,27 The NCCN guidelines are a statement ofevidence and consensus of the Palliative Care Panel

Member authors regarding their views of currently ac-cepted approaches to treatment.26,27 These guidelinesare defined as categories to evidence and are based onlower-level evidence where uniform NCCN consensusagrees that the strategies are appropriate.27 These guide-lines apply to all cancer diagnoses.26,27 The guidelinesare divided for patients whose life expectancy is yearsto months, months to weeks, and weeks to days (dyingpatient).26

When life expectancy is years to months, the NCCNguidelines recommendations include assessments, med-ications, and nonpharmacologic approaches. These areas follows: evaluate rate and severity of weight loss26;treat readily reversible causes of anorexia, for example,early satiety (eg, metoclopramide 10 mg before meals)and symptoms that interfere with intake such as dysgeu-sia, xerostomia, oral-pharyngeal candidiasis, mucositis,nausea and/or vomiting, dyspnea, depression, constipa-tion, and pain26; review and/or modify medications thatinterfere with intake26; evaluate for endocrine abnormal-ities such as hypogonadism, thyroid dysfunction, and met-abolic abnormalities (hypercalcemia and hyponatremia)7,26;consider appetite stimulants, for example, progestationalagents (eg, megestrol acetate 160-180 mg BID), corticoste-roids (eg, decadron 4 mg/d or prednisone 10-20 mg/d), andcannabinoids (dronabinol 5-20 mg/d)9,12,26; consider an ex-ercise program9,12; assess social and economic factors9,26;

FIGURE 3. Management of anorexia/cachexia by lifeexpectancy.3,9,12,26



consider a nutritional consultation9,26; consider nutritionsupport, enteral and parental feeding (as appropriate)26;and reassess the effectiveness of intervention and con-tinue to treat and monitor symptoms and QOL to deter-mine whether status warrants change in strategies withongoing assessments.26 If the patient shows weight stabi-lization or gain, improvement in symptoms that inter-fere with intake, improved energy level, and resolution ofmetabolic/endocrine abnormalities, continue to treat andmonitor symptoms and QOL to determine whether statuswarrants change in management.26 If unacceptable symp-toms continue, intensify palliative care interventions, pro-vide dietary consultation, and consider a clinical trial foranorexia-cachexia.26

When life expectancy is months to weeks or weeks todays, the NCCN guidelines are as follows: assess impor-tance of symptoms of anorexia and cachexia to patientand family, and if important consider short course of cor-ticosteroids26; focus on patient goals and preferences9,26;provide family with alternative way of caring for the pa-tient26; provide emotional support and treat for depres-sion (eg, mirtazapine 7.5-30 mg HS), if appropriate26;provide education and support to patient and family re-garding emotional aspects of withdrawal of nutritionalsupport26; recognize that discontinuation of nutrition isa value-laden issue and consider consultation with abioethicist or spiritual counselor9; educate the patientand family of the natural history of end-stage disease in-cluding the following points: absence of hunger and thirstis normal in the dying patient, nutritional support may notbe metabolized in patients with advanced disease,26 risksassociated with artificial nutrition (eg, fluid overload, in-fection, and hastened death),26 intravenous hydration mayincrease excretion of drug metabolites providing benefitsto the patient,26 symptoms like dry mouth should be treatedwith local measures (eg, mouth care and small amounts ofliquids),26 withholding or withdrawal of enteral or paren-teral nutrition is ethically permissible in this setting, andtherefore it will not cause exacerbation of symptoms andmay improve some symptoms26; and reassess the effective-ness of intervention. If acceptable, continue to monitor,treat, and reassess.26 If unacceptable, intensify palliativecare efforts and involve specialized palliative services orhospice.26 These guidelines provide current accepted prac-tical approaches to the treatment and care.3,9,12,26,28 Thegoal in palliative care is to minimize distress of symptomsand improve QOL.5,6

IMPACTS ON QUALITY OF LIFE

Quality of life is influenced by nutritional status.17,27 Theanorexia-cachexia syndrome is the most common syn-drome experienced by people with advanced stages ofdisease and seen in a subset of cancers, led by pancre-

atic and gastric cancer, but also lung, esophageal, colo-rectal, and head and neck cancer.5,27 The distress anddisruption in daily activities caused by anorexia-cachexialeave patients frail and weak, and their emaciated appear-ance is devastating for patients and their families.5,6,27,28

Quality of life encompasses four dimensions of well-being: physical, psychological, social, and spiritual.5,6,27,28

In some ways, the dimensions are distinct; however, thereis tremendous overlap. The impact of anorexia-cachexiaon QOL, seen in late-stage lung cancer is illustratedin Figure 4, adapted from the City of Hope Quality of LifeModel.28 Whether physical, psychological, social, or spiri-tual, a deficit that is identified in one domain impacts allother domains of QOL.27,28 The symptoms caused byanorexia-cachexia that impact physical well-being includeweight loss, decrease in muscle mass and body in fat, fa-tigue weakness, and dehydration.5,6,17,27,28 Anorexia-cachexia impacts psychological well-being with symptomsthat include anxiety, depression, worry, and fear.5,6,17,27,28

Physical and psychological distress may also impact socialwell-being for patients and family caregivers.27,28 Often,family caregivers continue to try to help the patient by re-minding and pleading with the patient to eat, as eating/feeding has great cultural meanings.5,6,17,27,28 The patient’sinability to eat can lead to irritability and become a sourceof tension, leading to family conflict and social isola-tion.5,6,17,27,28 Food we eat is derived from our cultural her-itage, and in some cultures, eating provides a way ofsocialization.5,6,17,27,28 Increasing weight loss may lead toalteration in body image.5,6,17,27,28 Spiritual well-being isimpacted by helplessness, hopelessness, and uncertainty

FIGURE 4. Anorexia-cachexia impacts the dimensions of quality oflife.28 Adapted from the City of Hope Quality of Life Model.28



and may cause one to reflect on meaning of his/her lifeand imminence of death.27,28

NURSING IMPLICATIONS

Palliative care is an approach that improves the QOL ofpatients and their families facing the problems associatedwith advanced illnesses such as lung cancer, through theprevention and relief of suffering by means of early iden-tification and impeccable assessment. Palliative care nursesplay a crucial role in ensuring that nutritional screening andassessments are conducted for all patients with lung can-cer, regardless of where the patient is in the disease trajec-tory. It should be done early and should be tailored to thegoals of the patient and family. Most importantly, contin-ued reassessment is necessary to evaluate the effectivenessof the response of interventions throughout the care. Man-agement strategies are multimodal; therefore, collaboratingwith other specialists in the palliative care team is neces-sary to minimize suffering for patients and their families.

In conclusion, anorexia-cachexia is a challenging syn-drome found in many cancers and other diseases. Furtherresearch is needed to continue testing of assessment andmanagement approaches. Meanwhile, nursing assessmentand reassessment of nutritional status can be used to imple-ment current strategies. Collaborating between palliativecare clinicians and researchers will allow the developmentof effective and practical guidelines, which is long overdue.The European Palliative Research Collaborative currently isthe primary source of evidence-based practice guidelinesof cancer cachexia with the overall aim of improving themanagement of pain, depression, and cachexia with trans-lational research.

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Documents

Management of Anorexia-Cachexia in Late-Stage Lung …Anorexia is the loss of appetite or desire to eat.11,12 In acute events, anorexia usually resolves with resolution of the illness,