The Patient With Cancer Cachexia

Many cancer patients experience cachexia. In collaboration with an interdisciplinary team including dietitians, oncology nurses are well positioned to implement proactive, multimodality interventions that improve clinical outcomes and quality of life for these patients.

Cancer cachexia, a common condition occurring in 50% to 75% of patients with cancer,[1,2] may lead to delayed, missed, or decreased treatments. It is a wasting syndrome involving loss of muscle and fat caused directly by tumor factors and/or indirectly by an abnormal response to tumor.[3] Cancer cachexia most commonly occurs in gastric (85% of patients), pancreatic (83%), non–small-cell lung (61%), small-cell lung (57%), prostate (57%), and colon (54%) cancers.[4] Notably, in 2011 an international group of experts on cancer cachexia reported that they had developed a consensus on the definition and classification of cancer cachexia. Fearon et al said they agreed that the “diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current body weight and height (body-mass index [BMI] < 20 kg/m²) or skeletal muscle mass (sarcopenia).” The experts agreed that cachexia can develop progressively, from precachexia, to cachexia, to refractory cachexia. Severity of cachexia, they said, can be classified based on the degree to which energy stores and body protein are depleted (BMI) in combination with the degree of ongoing weight loss. They noted that patient assessment for classification and treatment of cancer cachexia should include the domains of anorexia or reduced food intake, catabolic drive, muscle mass and strength, and functional and psychosocial impairment. The authors concluded that validation of this framework for defining and classifying cancer cachexia, “should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management” of this syndrome.[5]

Patient Overview

The patient, “Mr. L,” is a 53-year-old Caucasian male undergoing treatment for stage IV pancreatic cancer. In 2008, Mr. L presented for a workup due to a 20-pound weight loss and abdominal discomfort. He said that initially, he had presumed that the weight loss was caused by stress. Mr. L, a lawyer, was separated from his wife and in the process of filing for divorce and custody of his two 11-year-old children. His past medical history was unremarkable, with only a note about childhood asthma. The initial clinical impression was that the patient had either lymphoma or carcinoma. Further testing, including a CT scan of the chest, abdomen, and pelvis confirmed the diagnosis of pancreatic cancer with liver metastases.

To address Mr. L's weight loss and abdominal discomfort, a low-dose treatment of pancreases was prescribed which contains 8,000 USP units of lipase (pancrelipase, Creon). He was directed to take two tablets with meals. His initial chemotherapy treatment was a regimen of gemcitabine (Gemzar) and erlotinib (Tarceva), which was administered from November 2008 through January 2009. Upon progression of disease, this regimen was changed to gemcitabine, docetaxel, and capecitabine (Xeloda), which he received from January 2009 through June 2010. At that time, further progression was revealed and his regimen was changed again, to FOLFIRINOX (5-fluorouracil [5-FU], leucovorin, irinotecan, and oxaliplatin [Eloxatin]). Mr. L is continuing to receive this regimen and has stable disease, though he completed his 18th cycle with reduced doses of irinotecan and oxaliplatin, because of cytopenias.

Treatment Summary

On initial presentation, Mr. L weighed 217 pounds and his height was 70.75 inches, translating to a body mass index (BMI) of 29.7. (Individuals are considered within a normal weight range if their BMI, or body fat estimate based on height/weight is 18.5 to 24.5.) By this standard he would be classified as being overweight; his usual body weight was 235 pounds, however, so he had experienced an 8% weight loss in 1 month. Patients who have a 5% or greater weight loss in 1 month are considered at nutritional risk. In addition, Mr. L. presented with a disease that puts him at high risk for cancer-related cachexia. His weight of 217 pounds ± 2 pounds remained stable at presentation up until June 2010.

Beginning in June 2010, symptomatic changes occurred, with increasing complaints of abdominal discomfort, diarrhea, nausea, and poor appetite. At this time, Mr. L was found to have progressive disease. A weight decline to 210 pounds began in July 2010, and by August his weight had dropped to 198 pounds, for a 9% weight loss in 2 months. Along with treatment adjustment for disease progression, aggressive symptom management was initiated to address the diarrhea and nausea.

The previous prescription of pancreatic enzymes was increased to doses of 16,000 USP units of lipase, with two pills taken with meals and one pill taken with snacks. Commonly, people with pancreatic cancer have a pancreatic enzyme insufficiency. If weight loss is observed and the patient begins to complain of indigestion, flatulence, cramps and/or a change in stool characteristics, this condition and initiation of pancreatic enzyme replacement therapy should be considered. It is helpful to question the patient about whether stools are more frequent, loose or floating, and greasy in appearance.[6]

Mr. L was referred to the CARE (Cancer Appetite and Rehabilitation) Clinic at our cancer center in January 2011. The CARE Clinic provides comprehensive supportive care services through an interdisciplinary team that assesses and addresses the needs of cancer patients who experience cancer-related cachexia. Team members include a physician, nurse practitioner, dietitian, physical therapist, and speech and swallowing therapist. The purpose of the clinic is to reduce the effects of cancer cachexia and to improve the nutrition, function, symptom management, and quality of life of cancer patients. An individualized plan is developed to maintain an optimal nutritional status throughout treatment and survivorship.[7] Patients are referred to the CARE Clinic when they experience

• involuntary weight loss;
• increasing fatigue;
• difficulty with function and activities of daily living;
• difficult or painful swallowing; and/or
• speech impaired by muscle weakness.

The goals of the CARE Clinic are to

• prevent or reverse weight loss in cancer patients when possible;
• provide strategies to improve both speech and oral nutrition;
• improve cancer-related fatigue and function; and
• improve quality of life of cancer patients by managing symptoms.

At the CARE Clinic, Mr. L was assessed by the team and followed in monthly appointments. His main symptoms to be addressed were involuntary weight loss, fatigue, decreasing performance status, nausea, and depression. The nurse, registered dietitian, and physical therapist were instrumental in developing a plan of care to address each specific symptom. The registered dietitian educated Mr. L about eating strategies to reduce his nausea. (Useful nausea-management strategies to discuss with patients can be found on the National Cancer Institute's website.) He was given a nutritional supplement (Juven) that assists in the rebuilding of lean muscle mass. His symptoms subsided and his weight stabilized at 198 pounds through early January 2011. Burping, bloating, flatulence, and loose stools became more problematic. The cancer cachexia became more prominent with time, and his weight had plummeted to 184 pounds by mid January 2011 (see Table 1).

TABLE 1

Results of Patient Assessment

Mr. L admitted to feeling depressed and stated that he was forcing himself to eat but on some days it was just too difficult. Treatment with appetite stimulants such as megestrol acetate (Megace) and dronabinol (Marinol) has been unsuccessful. Because of his many symptoms indicating pancreatic enzyme insufficiency, the pancreatic enzymes were again dose-adjusted to 24,000 USP units of lipase (12 capsules) per day. He was prescribed mirtazapine (Remeron) for depression, and he was advised that his appetite might increase as a side effect of this agent.

Nutrition Management

For the patient with cancer cachexia, nutrition intervention is essential, but if body weight is the only parameter utilized for outcome, the intervention may seem futile. With cancer cachexia, individuals may or may not present with appetite loss, and there is muscle and fat breakdown. In the CARE Clinic, the registered dietitian assessed the patient's baseline nutritional status, muscle mass, and calorie expenditure using specialized tools. These tools may include bioelectrical impedance analysis (BIA) and indirect calorimetry, along with a review of additional laboratory parameters that may not be regularly obtained during the patient's routine physician and chemotherapy visits.

Tools for Patient Assessment

BIA is easy to perform in a clinical setting, and is a useful tool to assess for lean muscle wasting in the patient with cachexia. To perform a BIA, two conductors are attached to the patient and a small electric current is passed through the body. The resistance between the conductors provides a measure of body fat, because resistance to electricity is different between fat (a poor conductor), muscle, and skeletal tissue. Thus the technique in effect “compartmentalizes” body weight by lean muscle mass, fat, and extracellular tissue. The BIA measurement is reimbursable by most major insurance providers. Indirect calorimetry will help to personalize the nutrition care plan further by providing a patient's resting metabolic rate; a few handheld or easily transportable calorimetry tools are available (eg, BodyGem).

• Cancer cachexia originates from a combination of factors, including decreased dietary intake, anabolic endocrine deficiency, hyperexpression of catabolic elements, lack of physical activity, and the presence of comorbid conditions.

• Proactive, multimodality interventions to address cancer cachexia are an integral part of cancer therapy, with the aim of improving clinical outcomes and the patient's quality of life.

• In the case study described, the patient's disease and symptoms of cachexia were stabilized with treatment, strategic eating, nutritional supplements, pancreatic enzymes, and antidepressant therapy.

A useful screening tool in the busy ambulatory care setting is the Mini Nutritional Assessment (MMA), a six-item checklist that determines a patient's overall nutritional status by assessing for decline in food intake and weight loss (assigning scores of 0 for weight loss > 6.6 pounds, 1 for weight loss unknown, 2 for weight loss between 2.2 and 6.6 pounds, and 3 for no weight loss) during the last 3 months, BMI (or calf circumference if BMI is not available), mobility, dementia/depression, and psychological stress. Patients with total scores of 0 to 7 are classified as malnourished, those with scores of 8 to 11 are designated as being at risk of malnutrition, and those with a screening score of 12 to 14 points are deemed to have normal nutritional status. The MMA is available here.

Laboratory Values

In addition to obtaining the routine CBC (complete blood count) and chemistry profile, it is useful to obtain prealbumin values. Prealbumin, which has a short half-life, is an indicator of a patient's nutritional status and protein intake. Within the structure of the CARE Clinic, we further assess 25-hydroxy vitamin D levels, C-reactive protein levels, and testosterone levels in men. Prealbumin may be altered when inflammation is present, and assessment of C-reactive protein may confirm this. Cachexia may be exacerbated by the presence of inflammatory cytokines secreted by the cancer cells.

The role of vitamin D in cancer and other illnesses is being heavily researched, with the recommended daily allowance in vitamin D supplements still a subject of controversy. In November 2010 the Institute of Medicine (IOM) issued the report, “Dietary Reference Intakes for Calcium and Vitamin D,” updating its 1997 guidelines. The IOM reports recommends that adults 50 years of age and younger take 600 IU/day and those aged 51 years and older take 800 IU/day, with a suggested limit of 4,000 IU/day. These intake amounts translate to a serum level of 20 ng/mL, but some experts believe that target serum levels of vitamin D should be higher, in the 30–32 ng/mL range. Symptoms of vitamin D deficiency in addition to osteoporosis may include bone pain, muscle weakness, and cognitive impairment. Not surprisingly, Mr. L's vitamin D level was found to be low (see Table 1) due to fat malabsorption, and he was give supplementation with 50,000 IU of vitamin D twice a week for 6 weeks.

Testosterone deficiencies also may manifest as depression, decreased sense of well-being, decreased lean muscle mass, and decreased libido. This was not an issue for Mr. L, as his testosterone level was normal. All of these symptoms directly affect quality of life and performance status of the patient with cancer.

Nutritional recommendations need to be individualized and based on a patient's nutritional status and goals. While dietary adjustments may be sufficient for the patient with cachexia, administration of additional nutritional supplements may be warranted.

Specialized nutritional supplements (eg, Juven and Ensure Clinical Strength) can help patients to maintain and rebuild lean body mass, supporting their recovery and rehabilitation. The specialized compound in these supplements is HMB, or beta-hydroxy-beta-methylbutyrate, which regulates protein metabolism in muscle cells.[8]

Calorie modules in a variety of forms are available for supplemental protein, fat, or carbohydrates. Homemade smoothies can be excellent vehicles with which to deliver these nutritional supplements to patients in a taste-enhanced manner.

Nursing Management

Nursing management of the patient with cancer cachexia includes a complete history and physical examination. The history should include the cancer diagnosis, current cancer treatment, current medications, prior cancer diagnoses, weight loss, anorexia, and any related symptoms. Symptom-assessment tools such as the Edmonton Symptom Assessment Scale[9] can be useful in monitoring changes in symptoms when following a patient with cancer cachexia. Measurement of functional status with the Karnofsky performance status tool[10] is also a helpful way to monitor the impact of cancer cachexia on the patient's activities of daily living. Physical examination may reveal loss of muscle mass, indicated by temporal wasting and poor muscle tone. The patient's skin may be dry with poor turgor, and the nails may be brittle. Oral examination may reveal poor dentition, lesions, and dry mouth.[11]

The general approach toward management of cancer cachexia is based on the understanding of its multifactorial origin. Cancer cachexia originates from a combination of factors, including decreased dietary intake, anabolic endocrine deficiency, hyperexpression of catabolic elements, lack of physical activity, and presence of comorbid conditions.[12] Unfortunately, no single agent has been found to be effective in treating cancer cachexia. Several authors have recommended implementation of a combination of modalities by an experienced interdisciplinary team.[11,13–15] Investigation of a variety of agents to treat cancer cachexia, some novel and some approved for other indications, is ongoing.[16–19] The 6th Cachexia Conference, sponsored by the Society on Sarcopenia, Cachexia and Wasting Disorders, was held in Milan in December 2011 (click here for selected abstracts of preclinical and clinical studies presented at the conference).

Outcome

At the time of this writing, Mr. L was able to sustain a weight of 190 pounds. Although he would have preferred to weigh closer to 200 pounds, he was relieved to be able to maintain his weight. He reported that his episodes of diarrhea are now “rare,” and his nausea is minimal and mostly associated with chemotherapy. His appetite is fair but he is able to eat small frequent meals, incorporating high protein, calorically dense foods. He is now 3 years post-diagnosis of stage IV pancreatic cancer, and is receiving palliative chemotherapy with 5-FU, leucovorin, and reduced doses of irinotectan and oxaliplatin, due to cytopenias. His disease and symptoms of cachexia have been stabilized with treatment, strategic eating, nutritional supplements, pancreatic enzymes, and antidepressant therapy with mirtazapine (Remeron).

While his depression has improved, it is still evident; he has declined psychotherapy at this time. Mr. L. has maintained an ECOG performance status of 2 (ambulatory and capable of all self-care but unable to carry out work activities, up and about more than 50% of waking hours). He has stated, “I have been enjoying my time with the kids and hope to get out on my bike now that the weather is nice.” As of this writing, Mr. L is comfortably living with a chronic life-limiting disease and his symptoms are well controlled through the interdisciplinary management of his cachexia.

Discussion

Oncology nurses who work directly with patients on a daily basis, including chemotherapy nurses and oncology nurse practitioners, are particularly well positioned to have a positive impact on the lives of patients with cancer cachexia. Proactive, multimodality interventions to address cancer cachexia are an integral part of cancer therapy, with the aim of improving clinical outcomes and the patient's quality of life. Working in collaboration with other members of the interdisciplinary team, including the dietitian, nurses can improve outcomes by providing multiple strategies for assessing and managing cancer-related cachexia.

Financial Disclosure:The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

References

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