Nutrition in Cancer Care (PDQ®): Supportive care - Health Professional Information [NCI]

Basic Principles of Nutrition in Patients With Cancer

The nutrition status of patients with cancer can vary at presentation and through the continuum of cancer care. Many patients experience unintentional weight loss leading to a diagnosis of cancer.[1,2] Studies have reported malnutrition in 30% to 85% of patients with cancer.[3,4] In addition, malnutrition increases treatment toxicities, diminishes quality of life, and accounts for 10% to 20% of mortality in patients with cancer.[5][Level of evidence: IV] Because there has previously been no universal definition of malnutrition, reports of malnutrition occurrence vary and may be underreported or overreported in different populations. Historically, weight loss, low body mass index (BMI), and serum albumin levels have been used as surrogate markers for malnutrition.[6,7]

Emerging evidence supports that loss of lean body mass (sarcopenia) in patients with cancer is an independent risk factor for poorer outcomes, and that in the setting of obesity, unlike in other diseases where weight loss may be welcomed, inappropriate loss of weight may lead to loss of muscle mass and poorer outcomes.[1,2,8,9] However, there is no universal definition of sarcopenia, and there are no simple methods to identify the condition, limiting application in clinical practice.[10]

The leading nutrition societies of the United States and Europe have developed consensus guidelines regarding standardized definitions of malnutrition, and the U.S. societies have developed criteria for assessment of malnutrition including weight loss.[7,11,12]

Malnutrition

In 2010, the American Society for Parenteral and Enteral Nutrition (ASPEN) and the European Society for Clinical Nutrition and Metabolism published their proposed etiology-based definitions of malnutrition. These have been accepted by both groups and the Academy of Nutrition and Dietetics (the Academy).[7,11,13] The definitions and characteristics of malnutrition have also been accepted by the Academy's Oncology Nutrition Evidence Analysis Library Work Group.[14]

Etiology-based definitions of malnutrition include the following:

• Starvation-related malnutrition: pure chronic starvation (e.g., anorexia nervosa).
• Chronic disease–related malnutrition (e.g., organ failure, pancreatic cancer, rheumatoid arthritis, and sarcopenic obesity, resulting in mild to moderate inflammation).
• Acute disease–related or injury-related malnutrition (e.g., major infection, burns, trauma, and closed head injury, resulting in moderate to severe inflammation).

In 2012, ASPEN and the Academy released a joint statement regarding assessment of malnutrition.[12] The statement serves as a guide for nutrition assessment, including nutrition-focused physical assessment, to determine nutrition status. The assessment takes into consideration that obesity may mask malnutrition and that weight and BMI alone are not good surrogates for nutrition status.[13] The consensus statement provides the criteria for evaluating each of the following six potential indicators of malnutrition, with the recommendation that if two or more characteristics are present, the diagnosis of malnutrition is warranted.

• Insufficient energy intake.
• Weight loss.
• Loss of muscle mass.
• Loss of subcutaneous fat.
• Localized or generalized fluid accumulation that may sometimes mask weight loss.
• Diminished functional status as measured by hand grip strength.

Significant Weight Loss

Weight loss is often used as a surrogate for malnutrition. It has been correlated with adverse outcomes, including increased incidence and severity of treatment side effects and increased risk of infection, thereby reducing chances for survival.[15] Weight loss has been used as an indicator of poor prognosis in cancer patients.[16] One limitation of using weight loss as a surrogate for malnutrition is that it does not take into account the time course of the weight loss or the type of tissue loss.[7] In addition, weight may be affected by fluid shifts and may represent changes in hydration status, edema, or ascites rather than actual changes in fat and lean body mass.

The major nutrition societies in the United States have published criteria for the evaluation of weight loss over time and classifications as moderate or severe [12] (see Table 1). It is important that changes in weight be evaluated in the context of other clinical characteristics of underhydration or overhydration.

Anorexia and Cachexia

Anorexia, the loss of appetite or desire to eat, is typically present in 15% to 25% of all patients with cancer at diagnosis and may also occur as a side effect of treatments or related to the tumor itself. In an observational study of patients in outpatient clinics, anorexia was reported by 26% of patients receiving chemotherapy.[17] Anorexia can be exacerbated by chemotherapy and radiation therapy side effects such as taste and smell changes, nausea, and vomiting. Surgical procedures, including esophagectomy and gastrectomy, may produce early satiety, a premature feeling of fullness.[18] Depression, loss of personal interests or hope, and anxious thoughts may be enough to bring about anorexia and result in malnutrition.[19] Anorexia is an almost-universal symptom in individuals with widely metastatic disease [20,21] because of physiologic alterations in metabolism during carcinogenesis.

Anorexia can hasten the course of cachexia,[19] a progressive wasting syndrome evidenced by weakness and a marked and progressive loss of body weight, fat, and muscle. It can develop in individuals who have adequate protein and calorie intake but have primary cachexia whereby tumor-related factors prevent maintenance of fat and muscle. Patients with diseases of the gastrointestinal tract are particularly at risk of developing anorexia. For more information, see the Tumor metabolism section.

Sarcopenia

Sarcopenia is the condition of severe muscle depletion.[1] The importance of lean body mass is shown in studies of sarcopenia in cancer. A meta-analysis of 38 studies found that a low skeletal muscle index at cancer diagnosis was associated with worse survival in patients with solid tumors.[8] Other studies have also reported poorer overall survival and increased chemotherapy toxicity in patients with sarcopenia.[1,2,9] Sarcopenic obesity may represent a chronic low-level inflammatory state that, as with disease-related malnutrition, often limits the effectiveness of nutrition interventions and requires successful treatment of the underlying disease or condition.[11] Sarcopenia is associated with increased toxicity of treatment and therefore treatment interruptions and dose reductions. It is reported to occur in 50% of patients with advanced cancer.[22,23,24]

Sarcopenic obesity is the presence of sarcopenia in individuals with a high BMI (≥25 kg/m²), often precipitated by the loss of skeletal muscle and gain of adipose tissue. Sarcopenic obesity is an independent risk factor for poor prognosis.[1,25,26]

It is important to identify and anticipate malnutrition and other nutrition impact symptoms early. (Nutrition impact symptoms are a range of side effects of cancer and cancer treatment that impede oral intake, e.g., alterations in taste and smell, mucositis, dysphagia, stomatitis, nausea, vomiting, diarrhea, constipation, malabsorption, pain, depression, and anxiety.) Nutrition intervention improves outcomes by helping a patient do the following:[4,6,16,22,27,28,29]

• Maintain weight.
• Maintain the ability to stay on the intended treatment regimen with fewer changes.
• Improve quality of life.
• Produce better surgical outcomes.

It is suggested that the treating clinician assess baseline nutrition status and be aware of the possible implications of the various therapies. Patients receiving aggressive cancer therapies typically need aggressive nutrition management. For more information, see the Nutrition Screening and Assessment section.

In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.

References:

1. Martin L, Birdsell L, Macdonald N, et al.: Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol 31 (12): 1539-47, 2013.
2. Prado CM, Baracos VE, McCargar LJ, et al.: Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res 15 (8): 2920-6, 2009.
3. Bozzetti F, Mariani L, Lo Vullo S, et al.: The nutritional risk in oncology: a study of 1,453 cancer outpatients. Support Care Cancer 20 (8): 1919-28, 2012.
4. Hébuterne X, Lemarié E, Michallet M, et al.: Prevalence of malnutrition and current use of nutrition support in patients with cancer. JPEN J Parenter Enteral Nutr 38 (2): 196-204, 2014.
5. Muscaritoli M, Arends J, Bachmann P, et al.: ESPEN practical guideline: Clinical Nutrition in cancer. Clin Nutr 40 (5): 2898-2913, 2021.
6. Baldwin C, Spiro A, Ahern R, et al.: Oral nutritional interventions in malnourished patients with cancer: a systematic review and meta-analysis. J Natl Cancer Inst 104 (5): 371-85, 2012.
7. Marian M, August DA: Prevalence of malnutrition and current use of nutrition support in cancer patient study. JPEN J Parenter Enteral Nutr 38 (2): 163-5, 2014.
8. Shachar SS, Williams GR, Muss HB, et al.: Prognostic value of sarcopenia in adults with solid tumours: A meta-analysis and systematic review. Eur J Cancer 57: 58-67, 2016.
9. Kazemi-Bajestani SM, Mazurak VC, Baracos V: Computed tomography-defined muscle and fat wasting are associated with cancer clinical outcomes. Semin Cell Dev Biol 54: 2-10, 2016.
10. Beaudart C, McCloskey E, Bruyère O, et al.: Sarcopenia in daily practice: assessment and management. BMC Geriatr 16 (1): 170, 2016.
11. Jensen GL, Mirtallo J, Compher C, et al.: Adult starvation and disease-related malnutrition: a proposal for etiology-based diagnosis in the clinical practice setting from the International Consensus Guideline Committee. JPEN J Parenter Enteral Nutr 34 (2): 156-9, 2010 Mar-Apr.
12. White JV, Guenter P, Jensen G, et al.: Consensus statement: Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). JPEN J Parenter Enteral Nutr 36 (3): 275-83, 2012.
13. White JV, Guenter P, Jensen G, et al.: Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). J Acad Nutr Diet 112 (5): 730-8, 2012.
14. Levin R: Nutrition risk screening and assessment of the oncology patient. In: Leser M, Ledesma N, Bergerson S, et al., eds.: Oncology Nutrition for Clinical Practice. Oncology Nutrition Dietetic Practice Group, 2018, pp 25-32.
15. Vigano A, Watanabe S, Bruera E: Anorexia and cachexia in advanced cancer patients. Cancer Surv 21: 99-115, 1994.
16. McMahon K, Decker G, Ottery FD: Integrating proactive nutritional assessment in clinical practices to prevent complications and cost. Semin Oncol 25 (2 Suppl 6): 20-7, 1998.
17. Tong H, Isenring E, Yates P: The prevalence of nutrition impact symptoms and their relationship to quality of life and clinical outcomes in medical oncology patients. Support Care Cancer 17 (1): 83-90, 2009.
18. Rivadeneira DE, Evoy D, Fahey TJ, et al.: Nutritional support of the cancer patient. CA Cancer J Clin 48 (2): 69-80, 1998 Mar-Apr.
19. Bruera E: ABC of palliative care. Anorexia, cachexia, and nutrition. BMJ 315 (7117): 1219-22, 1997.
20. Langstein HN, Norton JA: Mechanisms of cancer cachexia. Hematol Oncol Clin North Am 5 (1): 103-23, 1991.
21. Tisdale MJ: Cancer cachexia. Anticancer Drugs 4 (2): 115-25, 1993.
22. Academy of Nutrition and Dietetics Oncology Expert Work Group: Nutrition and the Adult Oncology Patient. Chicago, Ill: Academy of Nutrition and Dietetics Evidence Analysis Library, 2013.
23. Cushen SJ, Power DG, Ryan AM: Nutrition assessment in oncology. Top Clin Nutr 30 (1): 103-19, 2015.
24. de van der Schueren M, Elia M, Gramlich L, et al.: Clinical and economic outcomes of nutrition interventions across the continuum of care. Ann N Y Acad Sci 1321: 20-40, 2014.
25. Prado CM, Lieffers JR, McCargar LJ, et al.: Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol 9 (7): 629-35, 2008.
26. Carneiro IP, Mazurak VC, Prado CM: Clinical Implications of Sarcopenic Obesity in Cancer. Curr Oncol Rep 18 (10): 62, 2016.
27. Aapro M, Arends J, Bozzetti F, et al.: Early recognition of malnutrition and cachexia in the cancer patient: a position paper of a European School of Oncology Task Force. Ann Oncol 25 (8): 1492-9, 2014.
28. Baldwin C, Weekes CE: Dietary counselling with or without oral nutritional supplements in the management of malnourished patients: a systematic review and meta-analysis of randomised controlled trials. J Hum Nutr Diet 25 (5): 411-26, 2012.
29. Ravasco P, Monteiro-Grillo I, Vidal PM, et al.: Dietary counseling improves patient outcomes: a prospective, randomized, controlled trial in colorectal cancer patients undergoing radiotherapy. J Clin Oncol 23 (7): 1431-8, 2005.

Impediments to Adequate Nutrition

Influences on nutrition status and risk of malnutrition include the following:[1]

• Baseline nutrition status.
• Disease site.
• Stage of disease.
• Treatment approach.

Treatment approaches, including surgery, chemotherapy, and radiation therapy, can have a direct (mechanical) negative effect and/or an indirect (metabolic) negative effect on nutrition status. The success of anticancer therapy is affected by the patient's nutrition status before and during treatment, which influences the patient's ability to tolerate therapy.

Oral intake is impeded by the following nutrition impact symptoms:[2]

• Anorexia.
• Alterations in taste and smell.
• Mucositis.
• Dysphagia.
• Stomatitis.
• Nausea.
• Vomiting.
• Diarrhea.
• Constipation.
• Malabsorption.
• Pain.
• Depression.
• Anxiety.

Preexisting comorbidities may also play a role in the development of cancer, e.g., alcohol abuse (head and neck cancer) and obesity (breast or prostate cancer), or may increase the risk of malnutrition at presentation.[3,4]

Tumor-Induced Effects on Nutrition Status

Tumors may have systemic or local effects that affect nutrition status, including hypermetabolism, malabsorption, dysmotility, and obstructions.[5]

Disease site

Nutrition complications are usually most notable and severe with tumors involving the digestive tract or head and neck, owing to mechanical obstruction or dysfunction. See Table 2 for common side effects of tumor locations.

Tumor metabolism

Nutrition status can be compromised in direct response to tumor-induced alterations in metabolism (i.e., cachexia). Tumor-induced weight loss occurs frequently in patients with solid tumors of the lung, pancreas, and upper gastrointestinal (GI) tract and less often in patients with breast cancer or lower GI cancer. Cachexia is also more common with more-advanced disease.

In 2011, an international group of experts developed a consensus definition of cachexia as "a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass...that cannot be fully reversed by conventional nutrition support and leads to progressive functional impairment."[11] They classified three stages of cachexia and provided diagnostic criteria:

• Precachexia: early signs (clinical and metabolic) that precede substantial weight loss.
• Cachexia: the presence of significant weight loss or sarcopenia in the absence of simple starvation.
  • Weight loss >5% over the past 6 months or
  • Body mass index <20 kg/m² and degree of weight loss >2% or
  • Sarcopenia and any degree of weight loss >2%.
• Refractory cachexia: cachexia that is clinically refractory, usually associated with advanced-stage cancer or rapid progression of disease that is unresponsive to treatment.

Although anorexia may also be present, the energy deficit alone does not explain the pathogenesis of cachexia. The etiology of cancer cachexia is not entirely understood, but several factors have been proposed.[12] Mediators, including cytokines, neuropeptides, neurotransmitters, and tumor-derived factors, are postulated to contribute to this syndrome.[13] Products of host tissues (e.g., tumor necrosis factor-alpha, interleukin-1, interleukin-6, interferon-gamma, and leukemia inhibitor factor) have been identified as mediators of this complex syndrome; also, tumor products (e.g., lipid-mobilizing factor and proteolysis-inducing factor [not established as definite in humans]) have a direct catabolic effect on host tissues.[14]

Altered metabolism of fats, proteins, and carbohydrates is evident in patients with cancer cachexia. Tumors may impair glucose uptake and glucose oxidation, leading to an increased glycolysis.[15] Weight loss can occur from a decrease in energy intake and/or an increase in energy expenditure. Although anorexia is a common symptom of patients with cancer, studies have shown that increased caloric intake, whether by the oral route or by supplementation with total parenteral nutrition, has failed to counteract the wasting process. This aberrant metabolic rate appears to be a direct response by the tumor and immune system to disrupt the pathways that regulate the body-weight regulation homeostasis loop.[13]

Treatment-Induced Effects on Nutrition Status

Cancer treatments may cause acute and chronic effects. Nutrition intervention is based on symptom management. Patients who maintain good nutrition are more likely to tolerate the side effects of treatment. Adequate calories and protein can help maintain patient strength and prevent body tissues from further catabolism. Side effects of cancer treatments vary among patients, depending on the type, length, and dose of treatments and the type of cancer being treated (see Table 3). Cancer treatment has toxic effects on the GI tract, including the following:

• Nausea.
• Vomiting.
• Constipation.
• Diarrhea.
• Xerostomia.
• Mucositis.
• Dysphagia.
• Loss of appetite.

Chemotherapy and hormone therapy

Chemotherapy and hormone therapy can be used as single agents or in combination, depending on the disease type and patient's health condition.[16,18] These agents are divided into several functional categories. For example, chemotherapy is a systemic treatment (not a localized treatment) that affects the whole body (not just a specific part) [19] and potentially causes more side effects when compared with localized treatments such as surgery and radiation therapy.

Common nutrition-related side effects include the following:

• Anorexia.
• Taste changes.
• Early satiety.
• Nausea.
• Vomiting.
• Mucositis/esophagitis.
• Diarrhea.
• Constipation.

Because cancer and the side effects of chemotherapy can greatly affect nutrition status, health care providers must anticipate possible problems and formulate a plan with the patient to prevent malnutrition and weight loss. Malnutrition and weight loss can affect a patient's ability to regain health and acceptable blood counts between chemotherapy cycles; this can directly affect the patient's ability to stay on treatment schedules, which is important for achieving a successful outcome. For more information, see the sections on Nutrition Screening and Assessment and Behavioral strategies for symptom management.

Patients receiving hormone suppression therapies are at risk of weight gain rather than weight loss. These patients may benefit from directed education to minimize weight gain and help reduce the risk of developing comorbidities associated with excess body weight.[20]

Radiation therapy

Radiation therapy causes localized symptoms. Some of the common nutrition-related side effects caused by irradiation include the following:[16]

• Changes in taste or ability to swallow.
• Nausea/vomiting.
• Changes in bowel movements (usually diarrhea).
• GI symptoms such as gas.

The side effects of radiation therapy depend on the area that is irradiated, total dose, fractionation, duration, and volume irradiated (see Table 4). Most side effects are acute, begin around the second or third week of treatment, and diminish 2 or 3 weeks after radiation therapy has been completed. Some side effects can be chronic and continue or occur after treatment has been completed.[21] For more information, see the Behavioral strategies for symptom management section.

Nutrition support during radiation therapy is vital. The effect of radiation therapy on healthy tissue in the treatment field can produce changes in normal physiologic function that may ultimately diminish a patient's nutrition status by interfering with ingestion, digestion, or absorption of nutrients.

Many nutrition-related side effects result from radiation therapy. Quality of life and nutrition intake can be improved by managing these side effects through appropriate medical nutrition therapy and dietary modifications. For example, medications such as pilocarpine (Salagen) may be useful in treating the xerostomia that accompanies radiation therapy targeting the head and neck.[22] This medicine may reduce the need for artificial saliva agents or other oral comfort agents such as hard candy or sugarless gum.

Surgery

For patients with most types of solid tumors, surgery is the only chance for a cure.[17] Although a tumor may be technically resectable, a meaningful recovery can depend on a patient's preoperative nutrition status. Patients who are malnourished at the time of surgery are at higher risk of postoperative morbidity and mortality and longer hospital stays.[25,26] If time permits or if the surgical procedure may be delayed safely, steps can be taken to identify patients who are moderately to severely malnourished before surgery and to correct macronutrient and micronutrient deficiencies before surgery.[6,25] Choosing the best method to correct a nutrition deficiency depends on GI tract function; options include oral liquid nutrition supplements, and enteral or parenteral nutrition support. For more information, see the Nutrition Screening and Assessment section.

Surgical treatment can increase occurrence of or worsen malnutrition. Common side effects of surgery, especially to the GI tract or head and neck, include decreased appetite, decreased ability to take food by mouth, and early satiety, all of which can lead to worsening preexisting malnutrition or may cause previously adequately nourished patients to become malnourished after surgery.[26]

Depending on the procedure, surgery can cause mechanical or physiologic barriers to adequate nutrition, such as a short gut that results in malabsorption after bowel resection.[6] In addition to these mechanical barriers, surgery frequently leads to an immediate catabolic response and changes the nutrient requirements necessary for wound healing and recovery at a time when baseline needs and requirements are often not being met.[4]

For more information about approaches to nutrition intervention and the appropriate use of enteral and parenteral nutrition support, see the Nutrition support section.

Biotherapy

Biotherapy is treatment to boost the immune system to help enhance the body's own response against cancer or to help repair normal cells damaged as a side effect of treatment.[18] Biotherapy includes growth factors, monoclonal antibodies, and vaccines. The symptoms of biotherapy that are most likely to impact nutrition status are fatigue, fever, nausea, vomiting, and diarrhea.[27]

Hemopoietic cell transplantation (HCT)

Patients receiving HCT can have special nutrition requirements. Before cell transplant, patients receive high-dose chemotherapy and may be treated with total-body irradiation.[28,29] In addition to the medications used during transplantation, these treatments frequently result in nutrition-related side effects, including mucositis and significant diarrhea, which may affect the ability to consume an adequate diet. Patients may also experience acute or chronic graft-versus-host disease (GVHD). GVHD may target the GI tract, liver, or skin, altering the body's ability to ingest and process adequate calories and protein.[28]

The goal of nutrition support is to maintain adequate nutrition status and protein stores. The American Society for Parenteral and Enteral Nutrition recommends that patients undergoing HCT who are malnourished and expected to be unable to ingest or absorb adequate nutrients for a prolonged period of time (>7–14 days) receive nutrition support; if a patient has a functioning GI tract, enteral nutrition is recommended.[28,29]

In addition, transplant patients are at very high risk of neutropenia, an abnormally small number of neutrophils in the blood that increases susceptibility to multiple infections. To reduce the risk of infections related to HCT, patients can receive dietary counseling regarding safe food handling and avoidance of foods that may pose an infection risk.[28,29] For more information about diet for immunocompromised patients, see the Reducing Risk of Foodborne Illness in Cancer Patients section.

References:

1. Levin R: Nutrition risk screening and assessment of the oncology patient. In: Leser M, Ledesma N, Bergerson S, et al., eds.: Oncology Nutrition for Clinical Practice. Oncology Nutrition Dietetic Practice Group, 2018, pp 25-32.
2. Wojtaszek CA, Kochis LM, Cunningham RS: Nutrition impact symptoms in the oncology patient. Oncology Issues 17 (2): 15-7, 2002.
3. Martin L, Birdsell L, Macdonald N, et al.: Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol 31 (12): 1539-47, 2013.
4. Huhmann M: Nutrition management of the surgical oncology patient. In: Leser M, Ledesma N, Bergerson S, et al., eds.: Oncology Nutrition for Clinical Practice. Oncology Nutrition Dietetic Practice Group, 2018, pp 135-42.
5. August DA, Huhmann M: Nutrition support of the cancer patient. In: Ross AC, Caballero B, Cousins RJ, et al., eds.: Modern Nutrition in Health and Disease. 11th ed. Wolters Kluwer Health/Lippincott Williams & Wilkins, 2014, pp 1194-1213.
6. McGuire M: Nutritional care of surgical oncology patients. Semin Oncol Nurs 16 (2): 128-34, 2000.
7. Leser M: Medical nutrition therapy for esophageal cancer. In: Leser M, Ledesma N, Bergerson S, et al., eds.: Oncology Nutrition for Clinical Practice. Oncology Nutrition Dietetic Practice Group, 2018, pp 181-6.
8. Gill C: Nutrition management for cancers of the gastrointestinal tract. In: Leser M, Ledesma N, Bergerson S, et al., eds.: Oncology Nutrition for Clinical Practice. Oncology Nutrition Dietetic Practice Group, 2018, pp 187-200.
9. Nguyen A, Nadler E: Medical nutrition therapy for head and neck cancer. In: Leser M, Ledesma N, Bergerson S, et al., eds.: Oncology Nutrition for Clinical Practice. Oncology Nutrition Dietetic Practice Group, 2018, pp 201-8.
10. Petzel MQB: Medical nutrition therapy for pancreatic and bile duct cancer. In: Leser M, Ledesma N, Bergerson S, et al., eds.: Oncology Nutrition for Clinical Practice. Oncology Nutrition Dietetic Practice Group, 2018, pp 219-28.
11. Fearon K, Strasser F, Anker SD, et al.: Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12 (5): 489-95, 2011.
12. Tisdale MJ: Pathogenesis of cancer cachexia. J Support Oncol 1 (3): 159-68, 2003 Sep-Oct.
13. Ramos EJ, Suzuki S, Marks D, et al.: Cancer anorexia-cachexia syndrome: cytokines and neuropeptides. Curr Opin Clin Nutr Metab Care 7 (4): 427-34, 2004.
14. Strasser F, Bruera ED: Update on anorexia and cachexia. Hematol Oncol Clin North Am 16 (3): 589-617, 2002.
15. Gambardella A, Tortoriello R, Tagliamonte MR, et al.: Metabolic changes in elderly cancer patients after glucose ingestion. The role of tumor necrosis factor-alpha. Cancer 79 (1): 177-84, 1997.
16. Grant BL: Nutritional effects of cancer treatment: chemotherapy, biotherapy, hormone therapy and radiation therapy. In: Leser M, Ledesma N, Bergerson S, et al., eds.: Oncology Nutrition for Clinical Practice. Oncology Nutrition Dietetic Practice Group, 2018, pp 97-114.
17. American Cancer Society: Cancer Surgery. Atlanta, Ga: American Cancer Society, 2019. Available online. Last accessed June 22, 2023.
18. LeFebvre KB, Stiver W: Overview of cancer and cancer treatment. In: Polovich M, Olsen M, LeFebvre KB, eds.: Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. 4th ed. Oncology Nursing Society, 2014, pp 1-16.
19. Fishman M, Mrozek-Orlowski M, eds.: Cancer Chemotherapy Guidelines and Recommendations for Practice. Oncology Nursing Press, 1999.
20. Olsen M, Davis PF, Douglas TT, et al.: Side effects of cancer therapy. In: Polovich M, Olsen M, LeFebvre KB, eds.: Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. 4th ed. Oncology Nursing Society, 2014, pp 171-436.
21. Donaldson SS: Nutritional consequences of radiotherapy. Cancer Res 37 (7 Pt 2): 2407-13, 1977.
22. Scarantino C, LeVeque F, Swann RS, et al.: Effect of pilocarpine during radiation therapy: results of RTOG 97-09, a phase III randomized study in head and neck cancer patients. J Support Oncol 4 (5): 252-8, 2006.
23. Romano MC: General symptom management: nutritional issues. In: Iwamoto RR, Haas ML, Gosselin TK, eds.: Manual for Radiation Oncology Nursing Practice and Education. 4th ed. Oncology Nursing Society, 2012, pp 80-94.
24. Harris DJ, Witt ME: Site-specific management: head and neck. In: Iwamoto RR, Haas ML, Gosselin TK, eds.: Manual for Radiation Oncology Nursing Practice and Education. 4th ed. Oncology Nursing Society, 2012, pp 122-44.
25. Huhmann MB, August DA: Perioperative nutrition support in cancer patients. Nutr Clin Pract 27 (5): 586-92, 2012.
26. Shim H, Cheong JH, Lee KY, et al.: Perioperative nutritional status changes in gastrointestinal cancer patients. Yonsei Med J 54 (6): 1370-6, 2013.
27. American Cancer Society Website. Atlanta, Ga: American Cancer Society, 2023. Available online. Last accessed June 22, 2023.
28. August DA, Huhmann MB; American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors: A.S.P.E.N. clinical guidelines: nutrition support therapy during adult anticancer treatment and in hematopoietic cell transplantation. JPEN J Parenter Enteral Nutr 33 (5): 472-500, 2009 Sep-Oct.
29. Macris PC: Medical nutrition therapy for hematopoietic cell transplantation. In: Leser M, Ledesma N, Bergerson S, et al., eds.: Oncology Nutrition for Clinical Practice. Oncology Nutrition Dietetic Practice Group, 2018, pp 157-64.

Nutrition Screening and Assessment

Optimizing nutrition for patients with cancer involves early detection of malnutrition or risk of malnutrition so that intervention may be initiated in the early stages of disease or treatment. The goal of nutrition screening is to rapidly identify patients who are at risk of developing malnutrition and refer them to a health care professional, ideally a registered dietitian, who can perform a complete nutrition assessment and implement a nutrition care plan.[1,2]

There are no standard definitions or indices of malnutrition. Historically, loss of weight or body mass index (BMI), low BMI, and low serum protein (e.g., albumin) have been used to identify patients with malnutrition. Without more context, these characteristics are not acceptable measures by which to determine malnutrition.[3,4,5] Weight changes alone cannot be used to determine nutrition status because weight changes do not account for fluid changes (dehydration, ascites, and edema) or disproportionate loss of lean body mass.[4,6] Likewise, evidence demonstrates that BMI is deceiving because it does not account for body composition (lean body mass vs. fat mass), and many patients with cancer may present with a normal or high body weight/BMI but have severe muscle depletion (i.e., sarcopenia).[7] The use of albumin, which is now recognized as being significantly influenced by inflammation, is also a poor measure of nutrition status and more likely suggestive of disease severity, not nutrition status.[4,8] Standardized definitions and cutoff points that designate malnutrition or cachexia are being developed; however, the true prevalence of malnutrition in the oncology population is unknown.

A growing body of literature examines the prevalence of malnutrition in obese cancer patients. In a study of clinical data obtained from 1,469 patients with metastatic primary cancers, 41.9% were identified as overweight or obese.[9] Upon assessment, 50% were at risk of being malnourished, and 12% were already malnourished at presentation. Malnutrition, even in the presence of obesity, has been found to be an independent predictor of survival,[9] with patients presenting with sarcopenic obesity having the poorest prognosis.[10] Therefore, these data suggest that the assessment of malnutrition among patients of every weight status is important.

Obesity has been shown to increase the risk of cancer recurrence, and it negatively impacts overall survival.[1,11,12] The prevalence of obesity is higher in adult cancer survivors than in those without a cancer history. Cancer survivors with the highest rates of increasing obesity are colorectal and breast cancer survivors and non-Hispanic Black individuals.[13] Emerging evidence supports the efficacy of intentional weight loss in overweight or obese cancer patients and survivors to reduce the risk of recurrent disease and improve prognosis, particularly among breast cancer patients.[14,15,16] Similar research is under way for patients with other obesity-related cancers.

Screening

Early recognition of nutrition-related issues is necessary for appropriate nutrition management of cancer patients. Nutrition screening can be performed with a validated tool before treatment begins and at regular intervals over the course of treatment.

Nutrition screening can be a simple process that may be completed by hospital staff or members of the community/ambulatory health care team, with the goal of early identification of individuals with or at risk of malnutrition.[1,5,17,18] Leading nutrition organizations—including the American Society for Parenteral and Enteral Nutrition, the European Society for Clinical Nutrition and Metabolism, and the Academy of Nutrition and Dietetics (the Academy)—recommend screening patients in both acute and ambulatory settings for risk of malnutrition.[8,17,18] The Academy's Oncology Nutrition Dietetic Practice Group, the Oncology Nursing Society, and the Association of Community Cancer Centers recommend screening all patients with cancer in the outpatient setting.[1,5] Because of a mandate from The Joint Commission that all patients admitted to the hospital undergo nutrition screening,[19] most acute care facilities have a screening system set up,[17] although such a system may not be specific to or validated in the oncology setting.

In the outpatient oncology setting, it is recommended that patients be screened initially before treatment begins and rescreened at planned intervals. Screening can most often coincide with the patient's treatment schedule, such as weekly during radiation therapy and as frequently as every 2 to 3 weeks during chemotherapy, before surgery, and at follow-up visits after completion of treatment or surgical recovery.[1,2,5]

The following five screening tools are validated for use in oncology:[5,20,21,22,23,24]

• The Malnutrition Screening Tool for Cancer Patients.
• The Malnutrition Universal Screening Tool.
• The Malnutrition Screening Tool (MST).
• The Patient-Generated Subjective Global Assessment (PG-SGA).
• The NUTRISCORE tool.

Only the MST and the PG-SGA have been validated for use in both inpatient and outpatient oncology settings. Several studies have validated use of the abridged PG-SGA (abPG-SGA) or short-form PG-SGA (PG-SGAsf), each of which is simply the section of the PG-SGA completed by the patient.[25,26]

The Nutrition Risk Screening-2002 has not been validated in the oncology setting, but it has been used in several studies of oncology patients. Scores are correlated to general outcomes associated with malnutrition, such as hospital length of stay, complications, and mortality.[2,3,18,27,28]

The NUTRISCORE tool utilizes the MST as a base but has additional items, including tumor location and treatment, that help improve sensitivity (97.3% vs. 84%) and specificity (95.9% vs. 85.6%). The authors used the PG-SGA as the reference for validation in the outpatient oncology setting, also finding that it took less time to complete the NUTRISCORE than it did to complete the PG-SGA.[24] When choosing a screening method, consider who will perform the screen, how much time may be devoted to the process, and what the process will be for referring the patient for a full nutrition assessment.[1] It is also ideal to use a validated tool. The two tools validated for both inpatient and outpatient in oncology settings are presented in further detail below.

MST

The MST is a short questionnaire comprising two questions. Depending on the answers, patients are stratified into two categories: at risk or not at risk.[23] The advantage of the MST is that it is quick to perform and may be completed by health care or administrative staff. It is well validated and consistently shows high sensitivity and specificity in identifying patients at risk of malnutrition.[29]

In screening, it is important to use a validated tool and to consider the needs of the clinical practice. In centers where a registered dietitian is available, the MST may be the screening tool of choice because it is quick and can be performed by many members of the office and practice staff. Patients found to be at risk may be referred to the dietitian for further assessment.

PG-SGA

The PG-SGA is the most commonly accepted tool for screening and assessment, backed by many studies and validated in both inpatient and outpatient oncology settings.[2,29] It is an in-depth tool, and most of the items are completed by the patient. There are four sections comprising 17 data points evaluating the following:

• Weight/weight history.
• Food intake.
• Symptoms.
• Activities/function.

The remainder of the PG-SGA is completed by a health care practitioner, accounting for information about disease and metabolic demand and the completion of a physical examination. The abPG-SGA and PG-SGAsf use only the section completed by the patient. Responses are then scored, and patients are stratified into the following four nutrition triage categories:[1,5]

• No intervention.
• Education by registered dietitian or other clinician.
• Intervention by registered dietitian.
• Critical need for improved symptom management.

The benefit of the PG-SGA (PG-SGAsf) is that it collects clinical information that can be helpful in the nutrition assessment. The drawback is that the PG-SGA takes more time to administer and requires a trained health care practitioner to complete the physical assessment portion. With validation of the short form, the need for physical examination is eliminated, and the practitioner's administration time is reduced.

In practices where a registered dietitian is not available, the PG-SGAsf may be more appropriate because it helps better determine which patients may receive sufficient information from the nurse, advanced-practice provider, or physician and which patients would best be referred to a registered dietitian for more in-depth assessment and intervention.

Assessment

Nutrition assessment is a comprehensive approach to evaluating and diagnosing nutrition problems and designing interventions.[17] A full nutrition assessment involves evaluation of the following six components:

• Food- and nutrition-related history.
• Anthropometric measurements.
• Biochemical data, medical tests, and procedures.
• Nutrition-focused physical assessment.
• Medical history.
• Treatment plan.

The assessment of anthropometric measurements evaluates weight loss, takes into account the time frame of weight loss, and is considered in the context of physical findings such as dehydration or fluid retention. Evaluation of food- and nutrition-related history ideally involves a dietitian obtaining a diet history and comparing intake with the patient's calculated energy needs.[2,6] The nutrition-focused physical assessment evaluates loss of muscle mass and subcutaneous fat, fluid accumulation, and potential micronutrient deficiencies. The physical examination of the following areas determines loss of subcutaneous fat or muscle:

Subcutaneous fat loss

• Orbit.
• Upper arm.
• Thoracic and lumbar regions.

Subcutaneous muscle loss

• Temple.
• Clavicle.
• Clavicle and acromion.
• Scapula.
• Dorsal hand.
• Patella.
• Anterior thigh.
• Posterior calf.

Within the nutrition assessment, the following factors are considered in diagnosing malnutrition:[8]

• Insufficient energy intake.
• Weight loss.
• Loss of muscle mass.
• Loss of subcutaneous fat.
• Localized or generalized fluid accumulation.
• Diminished functional status (e.g., grip strength).

In addition to the issues described above, the oncology nutrition assessment also takes into account the following:[5]

• Tumor location (current or anticipated mechanical function impairment).
• Current side effects/symptoms.
• Anticipated treatment/side effects.
• Anticipated duration of symptoms.
• Intent of treatment.

The goal of an oncology nutrition assessment is to collect the information necessary to determine current or anticipated nutrition issues and to formulate a plan with the patient, caregivers, and other members of the health care team involved with nutrition interventions. Additionally, this multidisciplinary team approach may also include metabolic, pharmacologic, and functional interventions to address and prevent the identified or anticipated nutrition issues.[1,5,30]

References:

1. Levin R: Nutrition risk screening and assessment of the oncology patient. In: Leser M, Ledesma N, Bergerson S, et al., eds.: Oncology Nutrition for Clinical Practice. Oncology Nutrition Dietetic Practice Group, 2018, pp 25-32.
2. Cushen SJ, Power DG, Ryan AM: Nutrition assessment in oncology. Top Clin Nutr 30 (1): 103-19, 2015.
3. Baldwin C, Spiro A, Ahern R, et al.: Oral nutritional interventions in malnourished patients with cancer: a systematic review and meta-analysis. J Natl Cancer Inst 104 (5): 371-85, 2012.
4. Marian M, August DA: Prevalence of malnutrition and current use of nutrition support in cancer patient study. JPEN J Parenter Enteral Nutr 38 (2): 163-5, 2014.
5. Academy of Nutrition and Dietetics Oncology Expert Work Group: Nutrition and the Adult Oncology Patient. Chicago, Ill: Academy of Nutrition and Dietetics Evidence Analysis Library, 2013.
6. Aapro M, Arends J, Bozzetti F, et al.: Early recognition of malnutrition and cachexia in the cancer patient: a position paper of a European School of Oncology Task Force. Ann Oncol 25 (8): 1492-9, 2014.
7. de van der Schueren M, Elia M, Gramlich L, et al.: Clinical and economic outcomes of nutrition interventions across the continuum of care. Ann N Y Acad Sci 1321: 20-40, 2014.
8. White JV, Guenter P, Jensen G, et al.: Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). J Acad Nutr Diet 112 (5): 730-8, 2012.
9. Gioulbasanis I, Martin L, Baracos VE, et al.: Nutritional assessment in overweight and obese patients with metastatic cancer: does it make sense? Ann Oncol 26 (1): 217-21, 2015.
10. Gonzalez MC, Pastore CA, Orlandi SP, et al.: Obesity paradox in cancer: new insights provided by body composition. Am J Clin Nutr 99 (5): 999-1005, 2014.
11. Rock CL, Doyle C, Demark-Wahnefried W, et al.: Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin 62 (4): 243-74, 2012 Jul-Aug.
12. Daniel CR, Shu X, Ye Y, et al.: Severe obesity prior to diagnosis limits survival in colorectal cancer patients evaluated at a large cancer centre. Br J Cancer 114 (1): 103-9, 2016.
13. Greenlee H, Shi Z, Sardo Molmenti CL, et al.: Trends in Obesity Prevalence in Adults With a History of Cancer: Results From the US National Health Interview Survey, 1997 to 2014. J Clin Oncol 34 (26): 3133-40, 2016.
14. Rock CL, Byers TE, Colditz GA, et al.: Reducing breast cancer recurrence with weight loss, a vanguard trial: the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial. Contemp Clin Trials 34 (2): 282-95, 2013.
15. Rock CL, Flatt SW, Byers TE, et al.: Results of the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial: A Behavioral Weight Loss Intervention in Overweight or Obese Breast Cancer Survivors. J Clin Oncol 33 (28): 3169-76, 2015.
16. Rock CL, Pande C, Flatt SW, et al.: Favorable changes in serum estrogens and other biologic factors after weight loss in breast cancer survivors who are overweight or obese. Clin Breast Cancer 13 (3): 188-95, 2013.
17. Mueller C, Compher C, Ellen DM, et al.: A.S.P.E.N. clinical guidelines: Nutrition screening, assessment, and intervention in adults. JPEN J Parenter Enteral Nutr 35 (1): 16-24, 2011.
18. Kondrup J, Allison SP, Elia M, et al.: ESPEN guidelines for nutrition screening 2002. Clin Nutr 22 (4): 415-21, 2003.
19. The Joint Commission: 2017 Comprehensive Accreditation Manual for Hospitals (CAMH). Joint Commission Resources, 2016.
20. Isenring E, Cross G, Daniels L, et al.: Validity of the malnutrition screening tool as an effective predictor of nutritional risk in oncology outpatients receiving chemotherapy. Support Care Cancer 14 (11): 1152-6, 2006.
21. Ottery FD: Rethinking nutritional support of the cancer patient: the new field of nutritional oncology. Semin Oncol 21 (6): 770-8, 1994.
22. Bauer J, Capra S, Ferguson M: Use of the scored Patient-Generated Subjective Global Assessment (PG-SGA) as a nutrition assessment tool in patients with cancer. Eur J Clin Nutr 56 (8): 779-85, 2002.
23. Ferguson M, Capra S, Bauer J, et al.: Development of a valid and reliable malnutrition screening tool for adult acute hospital patients. Nutrition 15 (6): 458-64, 1999.
24. Arribas L, Hurtós L, Sendrós MJ, et al.: NUTRISCORE: A new nutritional screening tool for oncological outpatients. Nutrition 33: 297-303, 2017.
25. Vigano AL, di Tomasso J, Kilgour RD, et al.: The abridged patient-generated subjective global assessment is a useful tool for early detection and characterization of cancer cachexia. J Acad Nutr Diet 114 (7): 1088-98, 2014.
26. Gabrielson DK, Scaffidi D, Leung E, et al.: Use of an abridged scored Patient-Generated Subjective Global Assessment (abPG-SGA) as a nutritional screening tool for cancer patients in an outpatient setting. Nutr Cancer 65 (2): 234-9, 2013.
27. Kondrup J, Rasmussen HH, Hamberg O, et al.: Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clin Nutr 22 (3): 321-36, 2003.
28. Orell-Kotikangas H, Österlund P, Saarilahti K, et al.: NRS-2002 for pre-treatment nutritional risk screening and nutritional status assessment in head and neck cancer patients. Support Care Cancer 23 (6): 1495-502, 2015.
29. Leuenberger M, Kurmann S, Stanga Z: Nutritional screening tools in daily clinical practice: the focus on cancer. Support Care Cancer 18 (Suppl 2): S17-27, 2010.
30. Huhmann MB, August DA: Review of American Society for Parenteral and Enteral Nutrition (ASPEN) Clinical Guidelines for Nutrition Support in Cancer Patients: nutrition screening and assessment. Nutr Clin Pract 23 (2): 182-8, 2008 Apr-May.

Nutrition Therapy

Goals of Nutrition Therapy

The goals of medical nutrition therapy are to do the following:[1]

• Address current cancer- and treatment-related issues.
• Minimize treatment-related side effects.
• Anticipate and manage acute, delayed, and late-occurring side effects of cancer and/or cancer treatment.

Goals must be individualized for each patient on the basis of the following:

• Nutrition status.
• Type and stage of disease.
• Comorbid conditions.
• Overall medical treatment plan.

Decisions about the best approach for therapy are informed by symptom severity and function of the gastrointestinal (GI) tract. Treatment could include multiple strategies based on these factors.

Nutrition goals during and after cancer therapy are integrated with goals related to nutrition status and the presence of malnutrition.[2]Table 5 summarizes nutrition goals on the basis of nutrition status, malnutrition as defined by current guidelines,[3] and stage of cancer treatment.

A healthy diet with an emphasis on plant-based foods, regular physical activity, and achievement of a healthy weight has been recommended for all patients after cancer treatment on the basis of extensive reviews of the evidence.[4,5] Evidence-based guidelines for a healthy diet for cancer risk reduction are available online from the American Institute for Cancer Research (AICR) and the American Cancer Society (ACS).

Methods of Nutrition Therapy

Prompt and aggressive nutrition intervention is required for patients with precachexia or cancer cachexia. Intervention is more likely to be effective when started early. Interventions include an individualized approach to oral, enteral, and parenteral nutrition using evidence-based recommendations, guidelines, and program and regulatory standards.

The dietitian works with the patient, caregivers, and members of the health care team to (1) improve compliance and the effectiveness of pharmacotherapy interventions prescribed to manage cancer and cancer treatment–related symptoms; and (2) counsel patients about behavioral strategies to alleviate nutrition impact symptoms.[1]

Counseling by a registered dietitian

The registered dietitian/nutritionist is an integral member of the oncology team in hospital and ambulatory settings. The Association of Community Cancer Centers Cancer Program Guidelines [7] specify having a registered dietitian work with patients and their families, especially those at risk of developing nutrition problems. Registered dietitians work with the patient, family, and medical team to manage nutrition and hydration status and maintain optimal nutrition status across the continuum of care through appropriate screening, assessment, and intervention.[8]

The registered dietitian does the following:[8,9]

• Provides individualized care to each patient with nutrition- and diet-related needs.
• Incorporates current research and utilizes evidence-based nutrition practice.
• Collaborates with the medical team to ensure integration of care with the overall treatment plan during active treatment and into survivorship.

Registered dietitians also serve as a resource for patients and communities, providing education related to reducing cancer risk and the risk of recurrence.[8,9] Intensive, individualized nutrition counseling requires nutrition professionals with specific experience in oncology.[9,10]

A systematic review of randomized controlled trials led to the recommendation that patients be referred for nutrition counseling because of strong evidence of its beneficial effects on the prevention and reduction of malnutrition.[11] Evidence also suggests that dietitian-led intervention is associated with increased survival.[12][Level of evidence: I][13]

A randomized controlled trial of 328 patients at a single institution in China assessed the inclusion of a dietitian and psychologist as part of the interdisciplinary team versus the standard of care. The standard of care team included the medical oncologist and oncology nurse, with referral, as needed, to a dietitian and/or psychologist. The patients in the intervention group met with the interdisciplinary team before starting chemotherapy and had follow-up visits at defined intervals throughout treatment until the time of death. Nutrition intervention (diet counseling and side-effect management, with or without oral nutrition supplements and tube feeding) and follow-up by the dietitian was standardized, based on initial nutrition risk screening scores. All participants received chemotherapy per standardized guidelines (including National Comprehensive Cancer Network), and there were no significant differences in patient demographics. Improvement in overall survival (median, 14.8 months vs. 11.9 months) occurred despite no statistically significant difference in progression-free survival. Secondary analysis also showed significant improvements in nutrition assessment scores at 9 weeks.[12][Level of evidence: I]

In a study of patients with unresectable pancreatic adenocarcinoma, participants had a weekly phone call with a registered dietitian for 8 weeks to discuss diet and management of disease-related side effects. They were also given oral nutritional supplements. Median survival was found to be significantly longer in weight-stable versus weight-losing subjects (8.6 months vs. 5.5 months).[13]

Despite consensus that referral for nutrition intervention should be early,[14] a multisite prospective study of clinical practice in Ireland found that the median time from cancer diagnosis to dietitian referral was 61 days. Moreover, by the time of referral to the dietitian, 66% of patients lost at least 5% body weight in the previous 3 to 6 months (36% of patients had at least 10% weight loss in the same time period). Considering weight loss history, patient clinical status, and known prior contacts with health care providers, dietitians determined that 45% of patients studied had "earlier opportunities for referral."[15]

Behavioral strategies for symptom management

Cancer and cancer treatment result in a range of side effects, described as nutrition impact symptoms, that impede oral intake. While some patients experience few of these effects, others may have multiple symptoms, including:

• Anorexia.
• Early satiety.
• Constipation.
• Diarrhea.
• Dysphagia.
• Fatigue.
• Mucositis.
• Nausea.
• Taste and smell changes.
• Xerostomia.

These symptoms can result in a decline in nutrition status and quality of life. Behavioral strategies are essential for alleviating the impact of these symptoms and promoting adequate nutrient intake; pharmacologic interventions may be used in combination with these strategies to minimize symptom severity.

The following lists describe behavioral strategies to help alleviate nutrition-related symptoms of cancer treatment. The information is based on the National Cancer Institute's (NCI's) Eating Hints: Before, During, and After Cancer Treatment and AICR's Dealing with Treatment Side Effects. Additional information about nutrition strategies during treatment is available from oncology-focused organizations such as ACS and AICR.[4,5,16]

• Loss of Appetite and Weight Loss
  • Eat small, frequent meals and healthy snacks throughout the day.
  • Eat foods that are high in protein and calories.
  • Eat high-protein foods first in your meal while your appetite is strongest—foods such as beans, chicken, fish, meat, yogurt, and eggs.
  • Add extra protein and calories to food. Cook with protein-fortified milk.
  • Drink milkshakes, smoothies, juices, or soups if you do not feel like eating solid foods.
  • Prepare and store small portions of favorite foods.
  • Seek foods that appeal to the sense of smell.
  • Experiment with different foods.
  • Eat larger meals when you feel well and are rested.
  • Sip only small amounts of liquids during meals.
  • Eat your largest meal when you feel hungriest, whether at breakfast, lunch, or dinner.
  • Be as active as possible to help develop a bigger appetite.
  • Consider asking your health practitioner about blenderized drinks with a high nutrient density.
  • Tell your doctor if you have eating problems such as nausea, vomiting, or changes in how foods taste and smell.
  • Perform frequent mouth care to relieve symptoms and decrease aftertastes.
  • Consider tube feedings if you are unable to sustain a certain amount of caloric intake to maintain strength.
• Constipation
  • Drink plenty of fluids each day, including water, warm juices, and prune juice.
  • Be active each day; take walks regularly.
  • Eat more fiber-containing foods.
  • Drink hot liquids to help relieve constipation, including coffee, tea, and warm milk.
  • Talk with your doctor before taking laxatives, stool softeners, or any medicine to relieve constipation.
  • Limit certain foods if you develop gas, including broccoli, cabbage, cauliflower, beans, and cucumbers.
  • Eat a large breakfast, including a hot drink and high-fiber foods.
  • Consider a fiber supplement.
• Diarrhea
  • Drink plenty of fluids to replace those lost from diarrhea, including water, ginger ale, and sports drinks.
  • Let carbonated drinks lose their fizz before you drink them.
  • Eat foods and liquids that are high in sodium and potassium.
    • Liquids: bouillon or fat-free broth.
    • Foods: bananas; canned apricots; and baked, boiled, or mashed potatoes.
  • Eat low-fiber foods.
  • Have foods and drinks at room temperature (neither too hot nor too cold).
  • Avoid foods such as:
    • High-fiber foods.
    • High-sugar foods.
    • Very hot or cold drinks.
    • Greasy, fatty, and fried foods.
    • Foods that can cause gas, such as carbonated beverages, cruciferous vegetables, legumes and lentils, and chewing gum.
    • Milk products (unless low lactose or lactose free).
    • Alcohol.
    • Spicy foods.
    • Caffeinated drinks.
    • Sugar-free products sweetened with xylitol or sorbitol.
• Dry Mouth
  • Sip water throughout the day.
  • Have very sweet or tart foods and drinks, such as lemonade, to help make more saliva.
  • Chew gum or suck on hard candy, ice pops, or ice chips; sugar free is best, but consult your doctor if you also have diarrhea.
  • Eat foods that are easy to swallow.
  • Moisten food with sauce, gravy, or salad dressing.
  • Do not drink any type of alcohol, beer, or wine.
  • Avoid foods that can hurt your mouth (i.e., spicy, sour, salty, hard, or crunchy foods).
  • Keep your lips moist with lip balm.
  • Rinse your mouth every 1 to 2 hours.
  • Do not use mouthwash that contains alcohol.
  • Do not use tobacco products, and avoid secondhand smoke.
  • Talk with your doctor or dentist about artificial saliva or other products to coat, protect, and moisten your throat and mouth.
• Lactose Intolerance
  • Prepare your own low-lactose or lactose-free foods.
  • Choose lactose-free or low-lactose milk products. Most grocery stores carry products (such as milk and ice cream) labeled "lactose free" or "low lactose."
  • Try products made with soy or rice (such as soy or rice milk and frozen desserts). These products do not contain any lactose.
  • Choose milk products that are low in lactose. Hard cheeses (such as cheddar) and yogurt are less likely to cause problems.
  • Try using lactase tablets when consuming dairy products. Lactase is an enzyme that breaks down lactose.
  • Avoid only the milk products that give you problems. Try small portions of milk, yogurt, or cheese to see if you can tolerate them.
  • Try calcium-fortified nondairy drinks and foods, which you can identify by food labels.
  • Eat more calcium-rich vegetables, including broccoli and greens.
• Nausea
  • Eat bland, soft, easy-to-digest foods rather than heavy meals.
  • Eat dry foods such as crackers, breadsticks, or toast throughout the day.
  • Eat foods that are easy on your stomach: white toast, plain yogurt, and clear broth.
  • Avoid strong food and drink smells.
  • Avoid eating in a room that has cooking odors or is overly warm; keep the living space comfortable but well ventilated.
  • Sit up or recline with your head raised for 1 hour after eating.
  • Rinse your mouth before and after eating.
  • Suck on hard candies such as peppermints or lemon drops if your mouth has a bad taste.
  • Eat five or six small meals each day instead of three large meals.
  • Do not skip meals and snacks; for many people, having an empty stomach makes nausea worse.
  • Choose foods that appeal to you. Do not force yourself to eat any food that makes you feel sick. Do not eat your favorite foods, to avoid linking them to being sick.
  • Have liquids throughout the day and drink slowly.
  • Sip only small amounts of liquids during meals because many people feel full or bloated if they eat and drink at the same time.
  • Have foods that are neither too hot nor too cold.
  • Eat dry toast or crackers before getting out of bed if you have nausea in the morning.
  • Plan the best times for you to eat and drink.
  • Relax before each cancer treatment.
  • Wear clothes that are loose and comfortable.
  • Keep a record of when you feel nausea and why.
  • Talk with your doctor about the use of antinausea medications.
• Sore Mouth
  • Choose foods that are easy to chew (i.e., soft foods such as milkshakes, scrambled eggs, and custards).
  • Cook foods until they are soft and tender.
  • Cut food into small pieces and use a blender or food processor to puree foods.
  • Drink with a straw to help push the drinks beyond the painful parts of your mouth.
  • Use a very small spoon to help you take smaller bites, which may be easier to chew.
  • Eat cold or room-temperature foods to avoid hurting your mouth with food that is too hot.
  • Suck on ice chips to help numb and soothe your mouth.
  • Avoid certain foods and drinks when your mouth is sore, such as:
    • Citrus foods.
    • Spicy foods.
    • Tomatoes and ketchup.
    • Salty foods.
    • Raw vegetables.
    • Sharp, crunchy foods.
    • Drinks that contain alcohol.
  • Do not use tobacco products.
  • Visit a dentist at least 2 weeks before starting biological therapy, chemotherapy, or radiation therapy to the head or neck.
  • Rinse your mouth 3 to 4 times a day. Mix ¼ teaspoon baking soda, ⅛ teaspoon salt, and 1 cup warm water for a mouth rinse.
  • Check your mouth each day for sores, white patches, or puffy and red areas.
  • Avoid items that can hurt or burn your mouth, such as:
    • Mouthwash containing alcohol.
    • Toothpicks or other sharp objects.
    • Tobacco products.
    • Alcohol.
• Sore Throat and Trouble Swallowing
  • Eat five or six small meals each day instead of three large meals.
  • Choose foods that are easy to swallow (e.g., milkshakes, scrambled eggs, and cooked cereal).
  • Choose foods and drinks that are high in protein and calories.
  • Cook foods until they are soft and tender.
  • Cut food into small pieces; use a blender or food processor to puree foods.
  • Moisten and soften foods with gravy, sauces, broth, or yogurt.
  • Sip drinks through a straw to make them easier to swallow.
  • Do not eat or drink things that can burn or scrape your throat, such as:
    • Hot foods and drinks.
    • Spicy foods.
    • Foods and juices that are high in acid.
    • Sharp or crunchy foods.
    • Drinks that contain alcohol.
  • Sit upright and bend your head slightly forward when eating or drinking, and stay upright for at least 30 minutes after eating.
  • Do not use tobacco products.
  • Consider tube feedings if your inability to eat is severely affecting your strength.
• Taste Changes
  • Use plastic utensils, and do not drink directly from metal containers if foods taste metallic.
  • Substitute poultry, fish, eggs, and cheese for red meat.
  • Consult a vegetarian or Chinese cookbook for useful nonmeat, high-protein recipes.
  • Add spices and sauces to foods; marinate foods.
  • Eat meat with something sweet, such as cranberry sauce, jelly, or applesauce.
  • Try tart foods and drinks.
  • Try to eat your favorite foods, if you are not nauseated. Try new foods when feeling your best.
  • If tastes are dull but not unpleasant, chew food longer to allow more contact with taste receptors.
  • If smells are an issue, keep foods covered, use cups with lids, drink through a straw, use a kitchen fan when cooking, or cook outdoors.
  • Use sugar-free lemon drops, gum, or mints when experiencing a metallic or bitter taste in the mouth. Use special mouthwashes.
  • Visit your dentist and maintain good oral hygiene.
• Vomiting
  • Do not eat or drink until vomiting stops.
  • Drink small amounts of clear liquids after vomiting stops.
  • Once you can drink clear liquids without vomiting, try full-liquid foods and drinks or those that are easy on your stomach.
  • Eat five or six small meals each day instead of three large meals.
  • Ask your doctor to prescribe medicine to prevent or control vomiting (antiemetic or antinausea medicines).
  • Sit upright and bend forward after vomiting.
• Weight Gain
  • Eat lots of fruits and vegetables, which are high in fiber and low in calories.
  • Eat foods that are high in fiber, such as whole-grain breads, cereals, and pasta.
  • Choose lean meats such as lean beef, pork trimmed of fat, or poultry without skin.
  • Choose low-fat milk products.
  • Eat less fat; limit amounts of butter, mayonnaise, desserts, fried foods, and other high-calorie foods.
  • Cook with low-fat methods such as broiling, steaming, grilling, or roasting.
  • Eat small portion sizes.
  • Eat less salt. Limiting salt will help you not retain water if your weight gain results from water retention.
  • Exercise daily.
  • Talk with your doctor before going on a diet to lose weight.
  • Pay attention to portion sizes; check food labels and the serving sizes listed.
  • Include and savor foods that you enjoy most so you feel satisfied.
  • Eat only when hungry. Consider psychological counseling or medications if you find yourself eating to address feelings of stress, fear, or depression, and try to find alternatives to eating out of boredom.

Oral nutrition supplements

Commercially available oral nutrition supplements (e.g., Boost, Ensure) are often used to improve the adequacy of nutrient intake.[8] These medical food products are not intended to serve as the sole source of nutrition, but to supplement energy, protein, fat, carbohydrate, and/or fiber intake, and also contribute to vitamin and mineral intake.[1] Recommendations for oral nutrition supplements are based on assessment of a patient's nutrition status, nutrient needs, GI function, clinical condition, diet, food preferences, comorbid conditions, and resources.

Patients with cancer need adequate protein to maintain and rebuild lean body mass. A systematic review of multinutrient, high-protein oral nutrition supplements found significant improvement in total energy and protein intake and reduced incidence of complications.[17] Specialized products are also available for use in clinical conditions requiring diet modifications. Research related to oral nutrition supplements and cancer patients has primarily focused on products containing fish oil/omega-3 fatty acids.[18,19,20] A systematic review of 38 studies did not find evidence to support a benefit of fish oil (supplements or enriched oral nutrition drinks) for the treatment of cachexia in advanced cancer.[21] A randomized trial evaluated the perioperative use of an oral nutrition drink enriched with eicosapentaenoic acid (EPA) (fish oil). In patients with resectable gastric cancer, supplementation did not change postoperative weight loss or complication rates.[22]

Although supplements containing fish oil alone do not seem to be beneficial in cachexia or surgery recovery, studies of immune-enhancing (IE) formulas containing fish oil, as well as arginine and nucleotides, suggest benefit for individuals undergoing GI surgery. A 2012 Cochrane review found significant reduction in postoperative complications and infections when IE oral supplements or enteral feeding were given before GI surgery.[23] A 2015 Bayesian network meta-analysis of randomized controlled trials also demonstrated reduction in postoperative infectious complications when IE formulas were used preoperatively. Studies of both preoperative and postoperative use found that noninfectious complications and hospital length of stay were also reduced.[24]

There is concern that long-term use of oral nutrition supplements can result in taste fatigue and decreased compliance with recommendations. A systematic review of compliance with oral nutrition supplements suggested that compliance is good, especially with higher-energy-density supplements.[25] Weaknesses of the review were that compliance was not the primary outcome variable of most of the evaluated studies, the analysis involved mean results from groups of subjects rather than individual compliance, and only 11% of the studies involved patients with cancer.

When oral supplements do not achieve nutrition goals, enteral and/or parenteral nutrition can be considered in the context of a patient's nutrition status and the overall medical treatment plan.[14,26]

Nutrition support

Nutrition support is the delivery of nutrition that bypasses oral intake. Every measure is employed to sustain patients and improve their condition through oral intake before nutrition support is considered.

• Enteral nutrition (tube feeding) provides nutrition directly into the GI tract.
• Parenteral nutrition is the intravenous (IV) infusion of nutrients.

The use of enteral and parenteral nutrition in the oncology population may be indicated when oral nutrition strategies are not possible or fail because of tumor location or severe side effects. Although nutrition support is not recommended as standard treatment, it may be beneficial for patients who are malnourished and expected to become unable to take in adequate nutrition by mouth for an extended period of time.[14,26] There are concerns that use of nutrition support will stimulate tumor growth and metastasis, but studies in humans are limited and show mixed results. However, if nutrition support is clinically indicated, it should not be withheld because of concerns about tumor promotion.[26,27]

Enteral nutrition is preferred over parenteral nutrition in most instances. Enteral nutrition continues to use the gut, is associated with fewer infectious complications, is often easier to administer, and is more cost-effective than parenteral nutrition.[26,27,28] Parenteral nutrition is indicated for patients with a malfunctioning GI tract, malabsorptive conditions, mechanical obstructions, severe bleeding, severe diarrhea, intractable vomiting, GI fistulas in locations difficult to bypass with an enteral tube, or inflammatory bowel processes such as prolonged ileus and severe enterocolitis.[27,28]

Indications for nutrition support include the following:[26,29]

• Patient is moderately to severely malnourished, will undergo major surgery, and is anticipated to not achieve adequate oral nutrition for at least 7 to 14 days postsurgery.
• Patient is malnourished and anticipated to have inadequate ingestion or absorption for 7 to 14 days or longer.
• Patient has a mechanical obstruction preventing food from reaching the small bowel for proper digestion and absorption.

Providing nutrition support routinely to patients undergoing chemotherapy or radiation therapy is not recommended; rather, nutrition support is reserved for patients who meet any of the criteria listed above. It is sometimes difficult to know which patients will have a prolonged period of inadequate oral intake or malabsorption and will benefit from nutrition support.[29] For patients undergoing head and neck radiation, investigators have validated an evidenced-based protocol for determining which patients are at high risk of nutrition deficiency and proactive placement of a gastrostomy tube.[30,31]

Although aggressive nutrition support has been shown to improve quality of life in patients with advanced cancer,[32] it is generally not recommended if life expectancy is less than a few weeks.[26] For some patients who have incurable disease and are undergoing anticancer treatment—such as those with bowel obstruction—nutrition support may be appropriate.[32] Practice guidelines are available from multinational groups, including the European Society for Clinical Nutrition and Metabolism (ESPEN) and the Multinational Association of Supportive Care in Cancer (MASCC). These guidelines endorse the use of nutrition support for individuals with advanced cancer who cannot ingest or absorb sufficient nutrients if their prognosis is more than 1 month, they are interested, and they have adequate cognitive and physical abilities.[33][Level of evidence: IV]

Potential benefits of nutrition support include the following:

• Improved quality of life.
• Decreased risk of death due to malnutrition.
• Decreased physical, cognitive, and psychological problems.

Investigators have suggested the following additional criteria for withholding nutrition support in patients with advanced disease:[32]

• Short estimated life expectancy (fewer than 2–3 months).
• Poor performance status as determined by a Karnofsky Performance Status score lower than 50% [34] or an Eastern Cooperative Oncology Group Performance Status grade of 3 or 4.[35]
• Severe organ dysfunction.
• Uncontrolled symptoms.
• Patient choice.

Enteral route and administration

Several effective methods for the delivery of enteral nutrition exist. Factors affecting a choice of the enteral route include the following:

• Anticipated length of need.
• Aspiration risk.
• Tumor location.
• Side effects.

Assessment of need is best performed early. If a malnourished patient requires surgery for an unrelated event, a feeding tube may be placed at that time to avoid an additional procedure.

Short-term feeding

For short-term feeding (<2 weeks), a nasoenteric tube may be best. The risk of aspiration is considered in the determination of the proper termination point of the tube, as follows:

• Stomach (nasogastric tube).
• Duodenum (nasoduodenal tube).
• Jejunum (nasojejunal tube). This is used for patients with an aspiration risk.

Tubes are constructed of silicone or polyurethane and can vary in length from 30 to 43 inches, with the shorter tubes used for nasogastric feedings. Diameters range from 5F catheters to 16F catheters. Tubes may have weighted tips to help passage through the gut. If a patient with cancer is at very high risk of aspiration, enteral nutrition may be contraindicated, and parenteral nutrition can be considered. Immunocompromised patients with mucositis, esophagitis, and/or herpetic, fungal, or candidiasis lesions in the mouth or throat may not be able to tolerate the presence of a nasoenteric tube.[27]

Longer-term feeding

For longer-term feeding (>4 weeks), direct enteral access is recommended. Percutaneous tubes may be placed endoscopically, surgically, or with fluoroscopy by interventional radiology.

Percutaneous tube placement has a number of advantages, including the following:[27]

• The diameter of the tube may be larger (15F–24F catheters), allowing easier and faster passage of formulas and medications.
• The risk of aspiration is lower because the tube is less likely to migrate into the esophagus.
• The risk of sinusitis or naso-esophageal erosion is lower.
• This route is more convenient and aesthetically pleasing to patients because they can conceal the tube.

Conversion to a skin-level button gastrostomy or jejunostomy may also be considered when longer-term support is anticipated.[27]

Infusion methods and formulas

Administration methods vary depending on where in the GI tract the tube terminates and may be affected by treatment side effects.

For tubes terminating in the stomach, a bolus or intermittent (gravity) drip may be possible and is preferable because it mimics normal feeding, requires less time and equipment, and offers greater flexibility to the patient. For tubes terminating in the duodenum or jejunum, an infusion pump is required because a slower administration rate is necessary. Feedings via a pump may be administered cyclically (<24 hours per day) or continuously.[27]

The following lists summarize infusion methods and considerations for initiation and administration of enteral nutrition.[27]

Bolus and Intermittent Feeding

• Caloric/nutrient and free-water requirements need to be determined to plan the feeding schedule.
• Bolus feedings can be offered 3 to 6 times each day; as much as 250 to 500 cc can be given over 10 to 15 minutes.
• Bolus feeding should be used only when the endpoint of the tube is in the stomach; it should never be used when feedings are delivered into the duodenum or jejunum. This precaution protects against gastric distention and dumping.
• A gravity drip from a bag or syringe with a slow push can be used to administer the formula.
• Diarrhea is a common side effect of this infusion method but can be controlled with a change in formula, additions to the formula, and a change in the amount of formula given over a finite period of time.

Continuous or Cyclic Drip Feeding

• Caloric/nutrient and free-water requirements need to be determined first to plan rate and time recommendations.
• Enteral feeding pumps provide reliable, constant infusion rates and decrease the risk of gastric retention.
• When no compounding factors are present, feeding into the stomach (25–30 cc/h) can start at a higher rate than feeding into the jejunum (10 cc/h); rates can be increased, with tolerance, every 4 to 6 hours until the rate reaches that needed to deliver the required caloric/nutrient needs.
• Continuous feeds can be cycled to run at night to allow greater flexibility and comfort. If it is physically possible, these nocturnal feeds can allow daytime oral or bolus feedings to meet nutrition goals and provide a more normal lifestyle.

Enteral formulas vary in nutrient composition and source. Most commercially available formulas are lactose free, kosher, and halal. Standard/polymeric formulations are appropriate for most patients. Semi-elemental and elemental formulas are available for patients with malabsorption who do not or will not tolerate standard formulas. In some cases, disease-specific (renal, pulmonary, and diabetic) formulas may be appropriate but in general are not necessary unless the patient has a demonstrated "failure" with standard formulas.

The use of whole-food blenderized formulas is gaining in popularity. Some products are commercially available, and there are published recipes for home-made formula. It is important for a dietitian to thoroughly review the nutrient content of these home-blenderized formulas to ensure adequacy.[27]

For patients in the perioperative setting, evidence supports the use of IE formulas. The most widely studied formula in this category contains a combination of arginine, omega-3 fatty acids, and nucleotides.[26,29] Studies suggest that use of these formulas for a very short time can reduce the incidence of surgical complications (infectious and noninfectious) and decrease the length of hospital stays.[23,26,36]

Parenteral route and administration

If parenteral nutrition is determined to be beneficial and appropriate, it can be administered via central or peripheral venous access. Many patients with cancer already have central IV catheters to accommodate multiple IV therapies. For patients who do not already have central line access or will not have it for a period of time, a peripheral catheter can be placed; however, care must be taken to avoid overuse of the peripheral IVs, as this can result in vessel sclerosis. To minimize venous complications, the use of peripheral parenteral nutrition is limited.[27]

Parenteral nutrition is a combination of dextrose (carbohydrate), amino acids (protein), and lipid emulsions (fat) with added electrolytes, vitamins, and trace elements. It is recommended that parenteral nutrition management include clinicians with expertise in nutrition support and be made up of a multidisciplinary team, including a registered dietitian and clinical pharmacist.[37]

Parenteral nutrition is typically initiated as a 24-hour infusion. After tolerance is established and generally after daily macronutrient goals are achieved, parenteral nutrition may be cycled (typically to an infusion time of 10–14 hours). For patients who will receive home parenteral nutrition, a cyclic infusion is preferred.[27] It is generally recommended that parenteral nutrition be initiated in the hospital and not at home. Only if the benefits of home initiation far outweigh the risks should it be considered, and only for patients who are hemodynamically stable, at low risk of refeeding syndrome, and nondiabetic.[38]

Pharmaceutical management of cancer-associated cachexia and weight loss

Many treatments have been suggested for cachexia-anorexia syndrome (CAS), but few of these treatments have resulted in consistent improvement, probably because of the multifactorial mechanisms involved.[39,40,41] Treatment must both reverse the metabolic disturbances in carbohydrate, lipid, and protein metabolism and treat the associated decrease in caloric intake.[42] Although most studies have examined single agents targeting one part of the multifactorial issues associated with CAS, many investigators have suggested that a multidrug approach might be more beneficial.[42,43,44] A summary of selected agents can be found in Table 6. Agents studied in CAS with inconclusive evidence or no statistically significant benefit to date include:

• Fluoxymesterone.[45]
• Oxandrolone.[46]
• Thalidomide.[47,48,49]
• Pentoxifylline.[50,51]
• Melatonin.[52,53]
• Omega-3 fatty acids.[54,55]
• Dronabinol.[56,57]
• Mirtazapine.[58]
• Fomoterol.[59,60]

Appetite stimulants

The first widely studied treatment issue has been anorexia associated with CAS. The use of agents that improve appetite and resultant caloric intake have been widely studied; these agents include corticosteroids, progesterone analogs, androgens, cannabinoids, and cyproheptadine.

Corticosteroids

Perhaps the earliest agents studied for the management of cancer cachexia are dexamethasone and prednisolone. Used in cancer treatment for their anti-inflammatory, antimalignancy, and antiemetic properties, steroids have produced side effects such as increased appetite and weight gain, probably because of their effects on the hypothalamus.

Several large placebo-controlled studies have shown increases in appetite and weight gain associated with steroid use in this setting.[61] However, the palliative effects on CAS have typically been short lived, and prolonged use is associated with significant side effects such as furthering catabolic effects on muscle, myopathy, joint disease, hyperglycemia, and hypertension.[62,63]

Progesterone analogs

Like steroids, progesterone antagonists are effective in improving appetite and weight in patients with AIDS-related cachexia and CAS.[59,64] A Cochrane review of 38 trials involving 4,304 patients reported the use of megestrol at doses of 160 to 800 mg per day for the treatment of CAS.[65] The only consistent benefits seen were weight gain and improved appetite. No definitive conclusions about other outcomes related to lean body mass, quality of life, or fatigue could be drawn. No improvement in survival was found.[65] In some clinical trials, the improvement was shown to be temporary increases in fat and water mass without concomitant improvements in lean body mass or quality of life.[66,67] However, another trial showed statistically significant improvements in weight, quality of life (as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30), appetite, and grip strength at 1- and 2-month intervals, compared with baseline.[68] In contrast, a 2022 meta-analysis of eight trials providing sufficient anthropometric data in the evaluation of megestrol in cancer-related anorexia concluded that megestrol acetate did not provide symptomatic improvement of anorexia/cachexia in patients with advanced cancer.[69] The overall pooled mean change in weight was 0.75 kg (95% confidence interval, -1.64 to 3.15 kg).

A placebo-controlled study looked at megestrol acetate at a dose of 7.5 mg/kg per day in 26 children with weight loss exceeding 5%. The megestrol group had a mean weight gain of 19.7% compared with weight loss of 1.2% (P = .003) in the placebo group.[70] Megestrol has also been studied in prophylaxis of weight loss, but again there was no demonstrated improvement in quality of life, lean muscle mass, or survival.[71,72,73] Concerns have also been raised about a possible increase in thromboembolic phenomena, sex hormone dysregulation, and suppression of the hypothalamic-pituitary axis, resulting in symptomatic adrenal insufficiency.[74]

Cannabinoids

Interest in the use of cannabinoids in CAS is ongoing because of their effects on appetite and potential benefit in HIV-related cachexia.[75] However, in a study of 469 patients comparing dronabinol alone versus megestrol acetate alone versus dronabinol plus megestrol acetate, dronabinol was inferior to megestrol acetate, and there was no additive effect when the drugs were used together.[56] A similar European trial of 243 patients comparing dronabinol with placebo also found no benefit.[57] For more information, see Cannabis and Cannabinoids.

Cyproheptadine

Cyproheptadine is a serotonin and histamine antagonist developed as an antihistamine. Side effects include increased appetite and weight gain.[76] A number of studies, mostly in children with a wide range of disorders associated with anorexia and weight loss, have shown that cyproheptadine results in significant improvements in weight in a number of studies.[77,78,79]

In a study of cyproheptadine use in children with CAS, one group of investigators evaluated 66 children with weight loss exceeding 5%.[78] The children received cyproheptadine at a daily dosage of 0.25 mg/kg. A total of 76% of the patients were classified as responders, experiencing either weight gain or no further weight loss. Patients also showed a significant increase in serum leptin levels.[78] Leptin is a protein hormone produced by adipocytes and is associated with body mass, particularly body fat. An increase in serum leptin has been correlated with an increase in body mass index.[78]

Anti-inflammatory agents

CAS is a multifactorial disorder that occurs in more than 50% of patients with advanced cancer. Increases in cytokines associated with cancer—including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1—have been shown to be important in the etiology of this disorder.[80] Pharmaceutical agents that inhibit the cytokine increases seen with cancer have been studied in patients with CAS.[81,82,83] EPA, an omega-3 fatty acid found in fish oil, has been used in a number of trials.[84] However, a meta-analysis failed to show a consistent improvement in CAS.[21] Similarly, several literature reviews of studies using nonsteroidal anti-inflammatory agents have failed to show conclusive evidence of efficacy.[85,86]

Specific targeted agents have also been studied. These include agents targeting TNF-alpha, such as etanercept, infliximab, and pentoxifylline, which, in small trials, have not had a significant impact.[87]

Several studies using thalidomide, a nonspecific antagonist to TNF, have been performed.[47,48,88,89,90] Thalidomide is of interest as a treatment for CAS because of its immunomodulatory properties.[47] A single-center, double-blind trial randomly assigned 50 pancreatic cancer patients who had lost at least 10% of their body weight to receive thalidomide 200 mg or placebo for 24 weeks. Patients who took thalidomide had a statistically significant reduction in weight loss compared with those who took a placebo.[48] A similarly sized trial of thalidomide 100 mg demonstrated no significant treatment effect.[47] Additionally, a Cochrane review on this topic reported insufficient evidence to support the use of thalidomide in patients with advanced cancer.[49]

Olanzapine

Olanzapine is an antipsychotic that blocks multiple neurotransmitters, including dopamine, serotonin, catecholamines, acetylcholine, and histamine.[91] Side effects of increased appetite and weight gain have been investigated in CAS with varying degrees of success. A single-center dose escalation trial evaluated the effect of olanzapine 2.5 mg to 20 mg daily on CAS and metabolic cytokines in 31 patients with advanced cancer receiving antineoplastic treatments.[92] A nonsignificant trend in attenuation of weight loss did not correlate with changes in metabolic cytokines. In contrast, a retrospective review evaluated food intake 3 days before and after initiation of olanzapine in 80 cancer patients hospitalized due to anorexia.[93] The average dose of olanzapine was 2.28 mg, which resulted in an increase in average relative food intake of 149%. Interestingly, olanzapine increased food intake by 143% in the cohort of patients who did not have preexisting nausea/vomiting.

A prospective trial randomly assigned 124 patients starting chemotherapy for untreated, locally advanced, or metastatic gastric, hepatopancreaticobiliary, and lung cancers to receive olanzapine 2.5 mg daily or placebo to evaluate appetite stimulation and weight gain.[94] At baseline, one-third of patients were underweight, almost all had anorexia, and over half reported greater than 5% weight loss from their prediagnosis weight. After 12 weeks, a greater proportion of patients in the olanzapine group versus the placebo group achieved more than 5% weight gain (60% vs. 9%, respectively). The olanzapine group also experienced a statistically significant improvement in appetite using a visual analog scale (43% vs. 13%, P < .001). The fraction of patients with grade 3 or greater adverse effects was lower with olanzapine than placebo (12% vs. 37%, P = .002), which resulted in the ability to increase chemotherapy to full dose in 12 of 16 patients.

Combination therapy

Given the multifactorial etiology of and multiple mechanisms involved in the development of CAS, it is possible that combining agents with different mechanisms of action might result in greater efficacy.[98,99] In one study, 332 patients diagnosed with CAS were randomly assigned to one of five treatment arms: medroxyprogesterone alone, oral supplementation with EPA, L-carnitine, thalidomide, or a combination of all four agents.[90] Investigators looked at lean body mass, resting energy expenditure, and fatigue. In this study, the combination arm was found to be superior. Another trial used megestrol alone versus megestrol plus L-carnitine, celecoxib, and antioxidants to treat 104 women with gynecologic malignancies.[98] Again, the combination arm was found to be superior. Conversely, a randomized placebo-controlled trial of megestrol acetate and placebo versus megestrol acetate and celecoxib found no significant difference in weight gain, quality of life, appetite score, or grip strength between the two groups. However, both groups showed improvements, suggesting a benefit of the single-agent use of megestrol acetate.[68]

Researchers also looked at the combination of formoterol, an anabolic beta-2 adrenergic agonist, and megestrol acetate in 13 patients. Six of seven evaluable patients achieved a major response, with increases in muscle mass.[59] Conversely, another study looking at megestrol plus meloxicam versus meloxicam plus EPA versus megestrol plus meloxicam and EPA showed no advantage to the three-drug regimen.[100] However, such combinations also may result in increased cumulative toxicity. For these reasons, there is no recommended combination at this time. In addition, combining drug therapy with nutrition support and increased physical activity may have even greater efficacy.

Summary of pharmaceutical treatment strategies

CAS is a complex, multifactorial complication of cancer and its therapy, resulting in weight loss and decreased lean body mass. As understanding of the mechanisms of CAS improves and new agents that selectively target proposed pathways become available, more efficacious treatments are expected to become available. Trials of new agents must be able to compare similar groups of patients. In addition, treating preventively in high-risk patients, as opposed to treating patients already experiencing CAS, may have better outcomes. Further clinical trials are essential to determine the best possible therapies.

References:

1. Grant BL: Academy of Nutrition and Dietetics Pocket Guide to the Nutrition Care Process and Cancer. Academy of Nutrition and Dietetics, 2015.
2. Hamilton C, Boyce VJ: Addressing malnutrition in hospitalized adults. JPEN J Parenter Enteral Nutr 37 (6): 808-15, 2013.
3. White JV, Guenter P, Jensen G, et al.: Consensus statement: Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition). JPEN J Parenter Enteral Nutr 36 (3): 275-83, 2012.
4. Kushi LH, Doyle C, McCullough M, et al.: American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin 62 (1): 30-67, 2012 Jan-Feb.
5. World Cancer Research Fund International: Cancer Prevention Recommendations. London, England: World Cancer Research Fund International, 2020. Available online. Last accessed June 22, 2023.
6. Rock CL, Doyle C, Demark-Wahnefried W, et al.: Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin 62 (4): 243-74, 2012 Jul-Aug.
7. Association of Community Cancer Centers: Cancer Program Guidelines. Association of Community Cancer Centers, 2012. Also available online. Last accessed June 22, 2023.
8. Clinical management and supportive care services. In: Association of Community Cancer Centers: Cancer Program Guidelines. Association of Community Cancer Centers, 2012, pp 10-25.
9. Robien K, Bechard L, Elliott L, et al.: American Dietetic Association: Revised standards of practice and standards of professional performance for registered dietitians (generalist, specialty, and advanced) in oncology nutrition care. J Am Diet Assoc 110 (2): 310-7, 317.e1-23, 2010.
10. Ravasco P: Nutritional approaches in cancer: relevance of individualized counseling and supplementation. Nutrition 31 (4): 603-4, 2015.
11. Lee JL, Leong LP, Lim SL: Nutrition intervention approaches to reduce malnutrition in oncology patients: a systematic review. Support Care Cancer 24 (1): 469-80, 2016.
12. Lu Z, Fang Y, Liu C, et al.: Early Interdisciplinary Supportive Care in Patients With Previously Untreated Metastatic Esophagogastric Cancer: A Phase III Randomized Controlled Trial. J Clin Oncol 39 (7): 748-756, 2021.
13. Davidson W, Ash S, Capra S, et al.: Weight stabilisation is associated with improved survival duration and quality of life in unresectable pancreatic cancer. Clin Nutr 23 (2): 239-47, 2004.
14. Arends J, Bachmann P, Baracos V, et al.: ESPEN guidelines on nutrition in cancer patients. Clin Nutr 36 (1): 11-48, 2017.
15. Lorton CM, Griffin O, Higgins K, et al.: Late referral of cancer patients with malnutrition to dietitians: a prospective study of clinical practice. Support Care Cancer 28 (5): 2351-2360, 2020.
16. Thompson KL, Elliott L, Fuchs-Tarlovsky V, et al.: Oncology Evidence-Based Nutrition Practice Guideline for Adults. J Acad Nutr Diet 117 (2): 297-310.e47, 2017.
17. Cawood AL, Elia M, Stratton RJ: Systematic review and meta-analysis of the effects of high protein oral nutritional supplements. Ageing Res Rev 11 (2): 278-96, 2012.
18. Sánchez-Lara K, Turcott JG, Juárez-Hernández E, et al.: Effects of an oral nutritional supplement containing eicosapentaenoic acid on nutritional and clinical outcomes in patients with advanced non-small cell lung cancer: randomised trial. Clin Nutr 33 (6): 1017-23, 2014.
19. van der Meij BS, Langius JA, Smit EF, et al.: Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment. J Nutr 140 (10): 1774-80, 2010.
20. de Aguiar Pastore Silva J, Emilia de Souza Fabre M, Waitzberg DL: Omega-3 supplements for patients in chemotherapy and/or radiotherapy: A systematic review. Clin Nutr 34 (3): 359-66, 2015.
21. Ries A, Trottenberg P, Elsner F, et al.: A systematic review on the role of fish oil for the treatment of cachexia in advanced cancer: an EPCRC cachexia guidelines project. Palliat Med 26 (4): 294-304, 2012.
22. Ida S, Hiki N, Cho H, et al.: Randomized clinical trial comparing standard diet with perioperative oral immunonutrition in total gastrectomy for gastric cancer. Br J Surg 104 (4): 377-383, 2017.
23. Burden S, Todd C, Hill J, et al.: Pre-operative nutrition support in patients undergoing gastrointestinal surgery. Cochrane Database Syst Rev 11: CD008879, 2012.
24. Song GM, Tian X, Zhang L, et al.: Immunonutrition Support for Patients Undergoing Surgery for Gastrointestinal Malignancy: Preoperative, Postoperative, or Perioperative? A Bayesian Network Meta-Analysis of Randomized Controlled Trials. Medicine (Baltimore) 94 (29): e1225, 2015.
25. Hubbard GP, Elia M, Holdoway A, et al.: A systematic review of compliance to oral nutritional supplements. Clin Nutr 31 (3): 293-312, 2012.
26. Huhmann MB, August DA: Perioperative nutrition support in cancer patients. Nutr Clin Pract 27 (5): 586-92, 2012.
27. Ryan A: Nutrition support in the oncology setting. In: Leser M, Ledesma N, Bergerson S, et al., eds.: Oncology Nutrition for Clinical Practice. Oncology Nutrition Dietetic Practice Group, 2018, pp 123-34.
28. Chow R, Bruera E, Chiu L, et al.: Enteral and parenteral nutrition in cancer patients: a systematic review and meta-analysis. Ann Palliat Med 5 (1): 30-41, 2016.
29. August DA, Huhmann MB; American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors: A.S.P.E.N. clinical guidelines: nutrition support therapy during adult anticancer treatment and in hematopoietic cell transplantation. JPEN J Parenter Enteral Nutr 33 (5): 472-500, 2009 Sep-Oct.
30. Brown TE, Crombie J, Spurgin AL, et al.: Improving guideline sensitivity and specificity for the identification of proactive gastrostomy placement in patients with head and neck cancer. Head Neck 38 (Suppl 1): E1163-71, 2016.
31. Brown TE, Getliffe V, Banks MD, et al.: Validation of an updated evidence-based protocol for proactive gastrostomy tube insertion in patients with head and neck cancer. Eur J Clin Nutr 70 (5): 574-81, 2016.
32. Cotogni P: Enteral versus parenteral nutrition in cancer patients: evidences and controversies. Ann Palliat Med 5 (1): 42-9, 2016.
33. Alderman B, Allan L, Amano K, et al.: Multinational Association of Supportive Care in Cancer (MASCC) expert opinion/guidance on the use of clinically assisted nutrition in patients with advanced cancer. Support Care Cancer 30 (4): 2983-2992, 2022.
34. Karnofsky DA, Abelmann WH, Craver LF, et al.: The use of the nitrogen mustards in the palliative treatment of carcinoma: with particular reference to bronchogenic carcinoma. Cancer 1 (4): 634-56, 1948.
35. Oken MM, Creech RH, Tormey DC, et al.: Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5 (6): 649-55, 1982.
36. Drover JW, Dhaliwal R, Weitzel L, et al.: Perioperative use of arginine-supplemented diets: a systematic review of the evidence. J Am Coll Surg 212 (3): 385-99, 399.e1, 2011.
37. Ayers P, Adams S, Boullata J, et al.: A.S.P.E.N. parenteral nutrition safety consensus recommendations. JPEN J Parenter Enteral Nutr 38 (3): 296-333, 2014 Mar-Apr.
38. Durfee SM, Adams SC, Arthur E, et al.: A.S.P.E.N. Standards for Nutrition Support: Home and Alternate Site Care. Nutr Clin Pract 29 (4): 542-555, 2014.
39. Molfino A, Formiconi A, Rossi Fanelli F, et al.: Cancer cachexia: towards integrated therapeutic interventions. Expert Opin Biol Ther 14 (10): 1379-81, 2014.
40. Mondello P, Mian M, Aloisi C, et al.: Cancer cachexia syndrome: pathogenesis, diagnosis, and new therapeutic options. Nutr Cancer 67 (1): 12-26, 2015.
41. von Haehling S, Anker SD: Treatment of cachexia: an overview of recent developments. J Am Med Dir Assoc 15 (12): 866-72, 2014.
42. Dingemans AM, de Vos-Geelen J, Langen R, et al.: Phase II drugs that are currently in development for the treatment of cachexia. Expert Opin Investig Drugs 23 (12): 1655-69, 2014.
43. Ma JD, Heavey SF, Revta C, et al.: Novel investigational biologics for the treatment of cancer cachexia. Expert Opin Biol Ther 14 (8): 1113-20, 2014.
44. Tuca A, Jimenez-Fonseca P, Gascón P: Clinical evaluation and optimal management of cancer cachexia. Crit Rev Oncol Hematol 88 (3): 625-36, 2013.
45. Loprinzi CL, Kugler JW, Sloan JA, et al.: Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. J Clin Oncol 17 (10): 3299-306, 1999.
46. Mattox TW: Treatment of unintentional weight loss in patients with cancer. Nutr Clin Pract 20 (4): 400-10, 2005.
47. Yennurajalingam S, Willey JS, Palmer JL, et al.: The role of thalidomide and placebo for the treatment of cancer-related anorexia-cachexia symptoms: results of a double-blind placebo-controlled randomized study. J Palliat Med 15 (10): 1059-64, 2012.
48. Gordon JN, Trebble TM, Ellis RD, et al.: Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut 54 (4): 540-5, 2005.
49. Reid J, Mills M, Cantwell M, et al.: Thalidomide for managing cancer cachexia. Cochrane Database Syst Rev (4): CD008664, 2012.
50. Mehrzad V, Afshar R, Akbari M: Pentoxifylline treatment in patients with cancer cachexia: A double-blind, randomized, placebo-controlled clinical trial. Adv Biomed Res 5: 60, 2016.
51. Goldberg RM, Loprinzi CL, Mailliard JA, et al.: Pentoxifylline for treatment of cancer anorexia and cachexia? A randomized, double-blind, placebo-controlled trial. J Clin Oncol 13 (11): 2856-9, 1995.
52. Del Fabbro E, Dev R, Hui D, et al.: Effects of melatonin on appetite and other symptoms in patients with advanced cancer and cachexia: a double-blind placebo-controlled trial. J Clin Oncol 31 (10): 1271-6, 2013.
53. Lissoni P, Paolorossi F, Tancini G, et al.: Is there a role for melatonin in the treatment of neoplastic cachexia? Eur J Cancer 32A (8): 1340-3, 1996.
54. Jatoi A, Rowland K, Loprinzi CL, et al.: An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort. J Clin Oncol 22 (12): 2469-76, 2004.
55. 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 21 (1): 129-34, 2003.
56. Jatoi A, Windschitl HE, Loprinzi CL, et al.: Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol 20 (2): 567-73, 2002.
57. Strasser F, Luftner D, Possinger K, et al.: Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol 24 (21): 3394-400, 2006.
58. Riechelmann RP, Burman D, Tannock IF, et al.: Phase II trial of mirtazapine for cancer-related cachexia and anorexia. Am J Hosp Palliat Care 27 (2): 106-10, 2010.
59. Greig CA, Johns N, Gray C, et al.: Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy. Support Care Cancer 22 (5): 1269-75, 2014.
60. Toledo M, Springer J, Busquets S, et al.: Formoterol in the treatment of experimental cancer cachexia: effects on heart function. J Cachexia Sarcopenia Muscle 5 (4): 315-20, 2014.
61. Kumar NB, Kazi A, Smith T, et al.: Cancer cachexia: traditional therapies and novel molecular mechanism-based approaches to treatment. Curr Treat Options Oncol 11 (3-4): 107-17, 2010.
62. Moertel CG, Schutt AJ, Reitemeier RJ, et al.: Corticosteroid therapy of preterminal gastrointestinal cancer. Cancer 33 (6): 1607-9, 1974.
63. Bruera E, Roca E, Cedaro L, et al.: Action of oral methylprednisolone in terminal cancer patients: a prospective randomized double-blind study. Cancer Treat Rep 69 (7-8): 751-4, 1985 Jul-Aug.
64. Hong S, Jeong IG, You D, et al.: Safety of megestrol acetate in palliating anorexia-cachexia syndrome in patients with castration-resistant prostate cancer. J Korean Med Sci 28 (5): 687-92, 2013.
65. Ruiz-García V, López-Briz E, Carbonell-Sanchis R, et al.: Megestrol acetate for cachexia-anorexia syndrome. A systematic review. J Cachexia Sarcopenia Muscle 9 (3): 444-452, 2018.
66. Malone M: Medications associated with weight gain. Ann Pharmacother 39 (12): 2046-55, 2005.
67. Busquets S, Serpe R, Sirisi S, et al.: Megestrol acetate: its impact on muscle protein metabolism supports its use in cancer cachexia. Clin Nutr 29 (6): 733-7, 2010.
68. Kouchaki B, Janbabai G, Alipour A, et al.: Randomized double-blind clinical trial of combined treatment with megestrol acetate plus celecoxib versus megestrol acetate alone in cachexia-anorexia syndrome induced by GI cancers. Support Care Cancer 26 (7): 2479-2489, 2018.
69. Lim YL, Teoh SE, Yaow CYL, et al.: A Systematic Review and Meta-Analysis of the Clinical Use of Megestrol Acetate for Cancer-Related Anorexia/Cachexia. J Clin Med 11 (13): , 2022.
70. Cuvelier GD, Baker TJ, Peddie EF, et al.: A randomized, double-blind, placebo-controlled clinical trial of megestrol acetate as an appetite stimulant in children with weight loss due to cancer and/or cancer therapy. Pediatr Blood Cancer 61 (4): 672-9, 2014.
71. Wen HS, Li X, Cao YZ, et al.: Clinical studies on the treatment of cancer cachexia with megestrol acetate plus thalidomide. Chemotherapy 58 (6): 461-7, 2012.
72. Simons JP, Aaronson NK, Vansteenkiste JF, et al.: Effects of medroxyprogesterone acetate on appetite, weight, and quality of life in advanced-stage non-hormone-sensitive cancer: a placebo-controlled multicenter study. J Clin Oncol 14 (4): 1077-84, 1996.
73. Argilés JM, Anguera A, Stemmler B: A new look at an old drug for the treatment of cancer cachexia: megestrol acetate. Clin Nutr 32 (3): 319-24, 2013.
74. Baracos VE: Clinical trials of cancer cachexia therapy, now and hereafter. J Clin Oncol 31 (10): 1257-8, 2013.
75. Gorter R: Management of anorexia-cachexia associated with cancer and HIV infection. Oncology (Williston Park) 5 (9 Suppl): 13-7, 1991.
76. Kardinal CG, Loprinzi CL, Schaid DJ, et al.: A controlled trial of cyproheptadine in cancer patients with anorexia and/or cachexia. Cancer 65 (12): 2657-62, 1990.
77. Moertel CG, Kvols LK, Rubin J: A study of cyproheptadine in the treatment of metastatic carcinoid tumor and the malignant carcinoid syndrome. Cancer 67 (1): 33-6, 1991.
78. Couluris M, Mayer JL, Freyer DR, et al.: The effect of cyproheptadine hydrochloride (periactin) and megestrol acetate (megace) on weight in children with cancer/treatment-related cachexia. J Pediatr Hematol Oncol 30 (11): 791-7, 2008.
79. Rodriguez L, Diaz J, Nurko S: Safety and efficacy of cyproheptadine for treating dyspeptic symptoms in children. J Pediatr 163 (1): 261-7, 2013.
80. Argilés JM, Olivan M, Busquets S, et al.: Optimal management of cancer anorexia-cachexia syndrome. Cancer Manag Res 2: 27-38, 2010.
81. Chasen M, Bhargava R, Hirschman S: Immunomodulatory agents for the treatment of cachexia. Curr Opin Support Palliat Care 8 (4): 328-33, 2014.
82. Solheim TS, Fearon KC, Blum D, et al.: Non-steroidal anti-inflammatory treatment in cancer cachexia: a systematic literature review. Acta Oncol 52 (1): 6-17, 2013.
83. Palus S, von Haehling S, Flach VC, et al.: Simvastatin reduces wasting and improves cardiac function as well as outcome in experimental cancer cachexia. Int J Cardiol 168 (4): 3412-8, 2013.
84. Di Girolamo FG, Situlin R, Mazzucco S, et al.: Omega-3 fatty acids and protein metabolism: enhancement of anabolic interventions for sarcopenia. Curr Opin Clin Nutr Metab Care 17 (2): 145-50, 2014.
85. Christoffersen T: Cancer, cachexia, prostanoids, and NSAIDs. Acta Oncol 52 (1): 3-5, 2013.
86. Reid J, Hughes CM, Murray LJ, et al.: Non-steroidal anti-inflammatory drugs for the treatment of cancer cachexia: a systematic review. Palliat Med 27 (4): 295-303, 2013.
87. Gueta I, Altman A, Shoenfeld Y: [The effect of blocking TNF-alpha in patients with cancer-related cachexia and anorexia]. Harefuah 149 (8): 512-4, 551, 550, 2010.
88. Tassinari D, Santelmo C, Tombesi P, et al.: Thalidomide in the treatment of cancer cachexia. J Palliat Care 24 (3): 187-9, 2008.
89. Davis M, Lasheen W, Walsh D, et al.: A Phase II dose titration study of thalidomide for cancer-associated anorexia. J Pain Symptom Manage 43 (1): 78-86, 2012.
90. Mantovani G, Macciò A, Madeddu C, et al.: Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. Oncologist 15 (2): 200-11, 2010.
91. Bymaster FP, Falcone JF, Bauzon D, et al.: Potent antagonism of 5-HT(3) and 5-HT(6) receptors by olanzapine. Eur J Pharmacol 430 (2-3): 341-9, 2001.
92. Naing A, Dalal S, Abdelrahim M, et al.: Olanzapine for cachexia in patients with advanced cancer: an exploratory study of effects on weight and metabolic cytokines. Support Care Cancer 23 (9): 2649-54, 2015.
93. Okamoto H, Shono K, Nozaki-Taguchi N: Low-dose of olanzapine has ameliorating effects on cancer-related anorexia. Cancer Manag Res 11: 2233-2239, 2019.
94. Sandhya L, Devi Sreenivasan N, Goenka L, et al.: Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer. J Clin Oncol 41 (14): 2617-2627, 2023.
95. Lexicomp Online. Hudson, Ohio: Lexi-Comp, Inc., 2021. Available online with subscription. Last accessed July 14, 2023.
96. Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, et al.: Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev (3): CD004310, 2013.
97. Willox JC, Corr J, Shaw J, et al.: Prednisolone as an appetite stimulant in patients with cancer. Br Med J (Clin Res Ed) 288 (6410): 27, 1984.
98. Macciò A, Madeddu C, Gramignano G, et al.: A randomized phase III clinical trial of a combined treatment for cachexia in patients with gynecological cancers: evaluating the impact on metabolic and inflammatory profiles and quality of life. Gynecol Oncol 124 (3): 417-25, 2012.
99. Vaughan VC, Martin P, Lewandowski PA: Cancer cachexia: impact, mechanisms and emerging treatments. J Cachexia Sarcopenia Muscle 4 (2): 95-109, 2013.
100. Kanat O, Cubukcu E, Avci N, et al.: Comparison of three different treatment modalities in the management of cancer cachexia. Tumori 99 (2): 229-33, 2013 Mar-Apr.

Nutrition in Advanced or Terminal Cancer

Patients with advanced disease often develop new or worsening nutrition-related side effects associated with disease progression, treatment, or both. In a large systematic review of symptom prevalence in patients with incurable cancer, the most common nutrition impact symptoms were the following:[1]

• Anorexia.
• Xerostomia.
• Constipation.
• Nausea.

These symptoms were present in a large subset of patients receiving care in various settings and in a small subset of patients in their last 2 weeks of life. Other symptoms among advanced-cancer patients receiving care in inpatient palliative care units,[2,3] cancer cachexia specialty clinics,[4] hospice, or nonhospice settings [3] included the following:[1,2,3,4]

• Bloating.
• Constipation.
• Dysphagia.
• Chewing difficulties.
• Early satiety.
• Mucositis.
• Taste changes.
• Vomiting.

In addition, advanced-cancer patients with pain and opioid-induced constipation (OIC) reported both physical and psychological distress related to the OIC.[5]

Clinically refractory cachexia develops as a result of very advanced cancer or rapidly progressive disease that is unresponsive to antineoplastic therapy. It is associated with active catabolism and weight loss that is unresponsive to nutrition therapy. At the end of life, patients often have severely restricted oral intake of food and fluids as part of the normal dying process.[6,7]

The primary objective of nutrition intervention in patients with advanced cancer is to conserve or restore the best possible quality of life and control any nutrition-related symptoms that cause distress.[7] However, issues related to nutrition and hydration for patients with advanced cancer may be a source of conflict among patients and their families and between patients and their health care teams.[7] Providers may need to address the natural history of cachexia in end-stage cancer and help patients cope with the emotional implications of cancer cachexia-anorexia.[8]

Goals of Nutrition Therapy in Advanced Cancer

Nutrition goals for a patient with advanced cancer may depend on the overall plan of care. These patients may be receiving anticancer therapy (with or without concurrent palliative care), may be receiving palliative care alone, or may be enrolled in hospice. Regardless of the care setting, patients are screened to determine the need for nutrition intervention. The Patient-Generated Subjective Global Assessment (PG-SGA) has been validated in cancer patients and addresses body weight history, food intake, symptoms, and functional status.[9,10] When palliative care is initiated early in the disease process, nutrition goals focus on supporting active treatment and aim to improve treatment outcomes, body composition, physical function, and symptom palliation.

As the focus of care shifts from cancer-modifying therapy to hospice or end-of-life care, nutrition goals may become less aggressive, with a shift toward comfort. Continued assessment and adjustment of nutrition goals and interventions is required throughout this continuum to meet the changing needs of the patient receiving palliative or hospice care services.[9]

Nutrition Intervention in Advanced Cancer

Ethical issues may arise when patients, families, or caregivers request artificial nutrition and hydration when there is no prospect of recovering from the underlying illness or benefiting appreciably from the intervention. When there is uncertainty about whether a patient will benefit from artificial nutrition, hydration, or both, a time-limited trial with clear, measurable endpoints may be useful. The caregiving team will explain that, as with other medical therapies, artificial nutrition and hydration can be stopped if the desired nutrition effects do not occur.[11]

Randomized controlled trials of enteral or parenteral nutrition in cancer patients receiving formal palliative care are lacking.[12] On the basis of available evidence and expert consensus, clinical guidelines recommend that the use of nutrition support therapy in advanced cancer be limited to carefully selected patients.[13,14] Patients who have demonstrated a favorable response to parenteral nutrition include those with the following:[15,13,16]

• A good performance status, such as a Karnofsky Performance Status score higher than 50%.
• Inoperable bowel obstruction.
• Minimal symptoms from disease involving major organs.
• Indolent disease.

If patients are to benefit from parenteral nutrition, they must be physically and emotionally capable of participating in their own care and have the following:[13]

• A life expectancy longer than 40 to 60 days.
• Strong social and financial support at home, including a dedicated informal caregiver.
• Failed trials of less-invasive medical therapies such as appetite stimulants and enteral feedings.

Patients with a life expectancy shorter than 40 days may be palliated with home intravenous (IV) fluid therapy, although this practice is controversial.[13]

Nutrition Considerations for the End of Life

Patients and caregivers often consider the provision of food and fluids to be basic care. However, the use of artificial nutrition and hydration at the end of life is a complex and controversial intervention that is influenced by clinical, cultural, religious, ethical, and legal factors. Patients and families often believe these interventions will improve quality and length of life, but evidence of clear benefit is lacking.[12,17] There are also potential burdens associated with this care, including the following:

• Sepsis (a risk of parenteral nutrition).
• Aspiration and diarrhea (a risk of tube feeding).
• Pressure sores and skin breakdown.
• Complications caused by fluid overload.

In addition, agitated or confused patients receiving artificial nutrition and hydration may need to be physically restrained to prevent them from removing a gastrostomy tube, nasogastric tube, or central IV line.[18]

Patients at the end of life who have increased difficulty with swallowing have less risk of aspiration with thick liquids than with thin liquids.[7] Thirst can often be alleviated with sips of water, ice chips, and good mouth care. In the last few days of life, the incidence of swallowing problems can be as high as 79% and include frequent coughing, anorexia, and problems with oral secretions.[19] Communication within the health care team and support of the family and caregivers is important in alleviating the distress concerning decreased food and fluid intake and in eliminating unrealistic expectations.[7]

For patients at the end of life, the goal of nutrition therapy is to alleviate symptoms rather than reverse nutrition deficits. The pleasure of tasting food and the social benefits of participating in meals with family and friends can be emphasized over increasing caloric intake.[6] A systematic review of practices and effects on cancer patients in the last week of life found no study supporting the use of artificial nutrition, and studies with artificial hydration had mixed results.[20] Studies on hydration with positive effects reported less chronic nausea and physical signs of dehydration, while studies with negative effects found more ascites and intestinal drainage. Other studies found no effect on terminal delirium, thirst, chronic nausea, or fluid overload.[20]

A well-designed randomized trial reported that hydration at 1 L/d for a week did not improve dehydration symptoms (fatigue, myoclonus, sedation, hallucinations) and provided no benefit in quality of life or survival.[21] A prospective evaluation of Japanese national guidelines for parenteral hydration at the end of life suggests little harm or benefit; however, patients expressed a high level of satisfaction and felt it was beneficial.[22] A subsequent study utilizing the Japanese guidelines reported that hydration-related symptoms (nausea, edema, dyspnea, abdominal pain/distention) were significantly improved, as were quality of life, global satisfaction, and feeling of benefit.[23]

The American Academy of Hospice and Palliative Medicine suggests that providers facilitate respectful and informed discussions about the effects of artificial nutrition and hydration near the end of life among physicians, other health care professionals, patients, and families.[11] It is incumbent on physicians and other health care providers to describe the options when the implementation, continuation, or discontinuation of artificial nutrition and hydration is being considered, and to establish goals of care with the patient and/or surrogate decision-maker. Ideally, patients will make their own decisions on the basis of a careful assessment of potential benefits and burdens, consistent with legal and ethical norms that permit patients to accept or forgo specific medical interventions.[11]

Ethical, Cultural, and Religious Issues in Medically Assisted Nutrition and Hydration in Advanced Cancer

Decisions about whether to provide artificial nutrition and hydration to patients in the late stages of life are complex and influenced by ethical, cultural, and religious issues, as well as by legal issues, clinical considerations, and patient and family preferences. The event of death itself, the manner in which it occurs, and the patient's quality of life are significant matters that have spiritual and psychological consequences for each person involved.[24]

A number of organizations have published guidelines on the ethical considerations about whether to forgo or discontinue hydration and nutrition support, including the following:

• American Medical Association.[25]
• American Academy of Hospice and Palliative Medicine.[11]
• Hospice and Palliative Nurses Association.[18]
• American Society for Parenteral and Enteral Nutrition.[26,27]
• Academy of Nutrition and Dietetics.[28]

These guidelines reflect judicial decisions that have supported the authority and liberty of the competent individual to refuse life-saving hydration and nutrition, the role of medical expertise, and respect for the dignity and values of the patient and family. For more information, see the sections on Artificial Hydration and Artificial Nutrition in Last Days of Life.

Religion and religious traditions provide a set of core beliefs about life events and an ethical foundation for clinical decision-making.[24] Although the fundamental principles of major religions provide perspectives on death and dying, decisions related to artificial nutrition and hydration remain complicated, varying even within the same major religion or faith tradition.

To provide an optimal and inclusive healing environment, all palliative team members need to be aware of their own spirituality and how it may differ from that of fellow team members and the patients and families they serve.[29,30] Clinical practice guidelines established by the National Consensus Project for Quality Palliative Care address spiritual, religious, and existential aspects of care.[31] One group of researchers [24] has provided insight into the principles and perspectives held by Roman Catholic, Jewish, Buddhist, and Islamic faith traditions. Another group [32] has provided an extensive analysis of how world religions formulate ethical decisions related to withdrawing treatment and determining when death has occurred.

Religious beliefs are often closely related to cultural views. Individuals living in the midst of a particular tradition can continue to be influenced by it, even if they have stopped believing in or practicing it.[32] In some cultures, individual autonomy is not the prevailing or predominant principle; some Asian, American Indian/Alaska Native, and Hispanic cultures favor family or community autonomy.[26] Distinguishing between majority and minority cultures is important. Patients may rely on religion and spirituality as important means to interpret and cope with illness.[33]

Religious and cultural preferences about artificial nutrition and hydration are expressions of a patient's autonomy and, in many cases, may outweigh clinical considerations. When these values conflict with clinical judgment, practitioners may work with the patient and/or surrogate in consulting with faith leaders and the patient's ethnic community, as well as the institutional ethics committee, to facilitate resolution.[26,27]

References:

1. Teunissen SC, Wesker W, Kruitwagen C, et al.: Symptom prevalence in patients with incurable cancer: a systematic review. J Pain Symptom Manage 34 (1): 94-104, 2007.
2. Bovio G, Montagna G, Bariani C, et al.: Upper gastrointestinal symptoms in patients with advanced cancer: relationship to nutritional and performance status. Support Care Cancer 17 (10): 1317-24, 2009.
3. Mercadante S, Aielli F, Adile C, et al.: Prevalence of oral mucositis, dry mouth, and dysphagia in advanced cancer patients. Support Care Cancer 23 (11): 3249-55, 2015.
4. Del Fabbro E, Hui D, Dalal S, et al.: Clinical outcomes and contributors to weight loss in a cancer cachexia clinic. J Palliat Med 14 (9): 1004-8, 2011.
5. Dhingra L, Shuk E, Grossman B, et al.: A qualitative study to explore psychological distress and illness burden associated with opioid-induced constipation in cancer patients with advanced disease. Palliat Med 27 (5): 447-56, 2013.
6. Dev R, Hui D, Chisholm G, et al.: Hypermetabolism and symptom burden in advanced cancer patients evaluated in a cachexia clinic. J Cachexia Sarcopenia Muscle 6 (1): 95-8, 2015.
7. Orrevall Y: Nutritional support at the end of life. Nutrition 31 (4): 615-6, 2015.
8. Hopkinson JB: The emotional aspects of cancer anorexia. Curr Opin Support Palliat Care 4 (4): 254-8, 2010.
9. Trentham K: Nutrition management of oncology patients in palliative and hospice settings. In: Leser M, Ledesma N, Bergerson S, et al., eds.: Oncology Nutrition for Clinical Practice. Oncology Nutrition Dietetic Practice Group, 2018, pp 241-8.
10. Nutrition screening and determining malnutrition risk in adults with cancer. In: Grant BL: Academy of Nutrition and Dietetics Pocket Guide to the Nutrition Care Process and Cancer. Academy of Nutrition and Dietetics, 2015, pp 15-27.
11. Statement on Artificial Nutrition and Hydration Near the End of Life. Chicago, Ill: American Academy of Hospice and Palliative Medicine, 2013. Available online. Last accessed Nov. 16, 2023.
12. Good P, Richard R, Syrmis W, et al.: Medically assisted nutrition for adult palliative care patients. Cochrane Database Syst Rev (4): CD006274, 2014.
13. August DA, Huhmann MB; American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors: A.S.P.E.N. clinical guidelines: nutrition support therapy during adult anticancer treatment and in hematopoietic cell transplantation. JPEN J Parenter Enteral Nutr 33 (5): 472-500, 2009 Sep-Oct.
14. Bozzetti F, Arends J, Lundholm K, et al.: ESPEN Guidelines on Parenteral Nutrition: non-surgical oncology. Clin Nutr 28 (4): 445-54, 2009.
15. Karnofsky DA, Abelmann WH, Craver LF, et al.: The use of the nitrogen mustards in the palliative treatment of carcinoma: with particular reference to bronchogenic carcinoma. Cancer 1 (4): 634-56, 1948.
16. Soo I, Gramlich L: Use of parenteral nutrition in patients with advanced cancer. Appl Physiol Nutr Metab 33 (1): 102-6, 2008.
17. Good P, Richard R, Syrmis W, et al.: Medically assisted hydration for adult palliative care patients. Cochrane Database Syst Rev (4): CD006273, 2014.
18. HPNA position statement: artificial nutrition and hydration in advanced illness. J Hosp Palliat Nurs 14 (3): 173-6, 2012.
19. Bogaardt H, Veerbeek L, Kelly K, et al.: Swallowing problems at the end of the palliative phase: incidence and severity in 164 unsedated patients. Dysphagia 30 (2): 145-51, 2015.
20. Raijmakers NJ, van Zuylen L, Costantini M, et al.: Artificial nutrition and hydration in the last week of life in cancer patients. A systematic literature review of practices and effects. Ann Oncol 22 (7): 1478-86, 2011.
21. Bruera E, Hui D, Dalal S, et al.: Parenteral hydration in patients with advanced cancer: a multicenter, double-blind, placebo-controlled randomized trial. J Clin Oncol 31 (1): 111-8, 2013.
22. Yamaguchi T, Morita T, Shinjo T, et al.: Effect of parenteral hydration therapy based on the Japanese national clinical guideline on quality of life, discomfort, and symptom intensity in patients with advanced cancer. J Pain Symptom Manage 43 (6): 1001-12, 2012.
23. Nakajima N, Takahashi Y, Ishitani K: The volume of hydration in terminally ill cancer patients with hydration-related symptoms: a prospective study. J Palliat Med 17 (9): 1037-41, 2014.
24. Jahn Kassim PN, Alias F: Religious, Ethical and Legal Considerations in End-of-Life Issues: Fundamental Requisites for Medical Decision Making. J Relig Health 55 (1): 119-34, 2016.
25. AMA Code of Medical Ethics' Opinions on Care at the End of Life. Opinion 2.20 - Withholding or Withdrawing Life-Sustaining Medical Treatment. Virtual Mentor 13 (12): 1038-40, 2013. Also available online. Last accessed June 22, 2023.
26. Geppert CM, Andrews MR, Druyan ME: Ethical issues in artificial nutrition and hydration: a review. JPEN J Parenter Enteral Nutr 34 (1): 79-88, 2010 Jan-Feb.
27. Barrocas A, Geppert C, Durfee SM, et al.: A.S.P.E.N. ethics position paper. Nutr Clin Pract 25 (6): 672-9, 2010.
28. O'Sullivan Maillet J, Baird Schwartz D, Posthauer ME, et al.: Position of the academy of nutrition and dietetics: ethical and legal issues in feeding and hydration. J Acad Nutr Diet 113 (6): 828-33, 2013.
29. Ferrell B, Otis-Green S, Economou D: Spirituality in cancer care at the end of life. Cancer J 19 (5): 431-7, 2013 Sep-Oct.
30. Dahlin C, ed.: Clinical Practice Guidelines for Quality Palliative Care. 3rd ed. National Consensus Project for Quality Palliative Care, 2013. Also available online. Last accessed Nov. 16, 2023.
31. National Consensus Project for Quality Palliative Care: Clinical Practice Guidelines for Quality Palliative Care. 4th ed. National Coalition for Hospice and Palliative Care, 2018. Also available online. Last accessed Nov. 16, 2023.
32. Setta SM, Shemie SD: An explanation and analysis of how world religions formulate their ethical decisions on withdrawing treatment and determining death. Philos Ethics Humanit Med 10: 6, 2015.
33. El Nawawi NM, Balboni MJ, Balboni TA: Palliative care and spiritual care: the crucial role of spiritual care in the care of patients with advanced illness. Curr Opin Support Palliat Care 6 (2): 269-74, 2012.

Reducing Risk of Foodborne Illness in Cancer Patients

The wide range of practices related to neutropenic diets reflects the lack of evidence regarding the efficacy of dietary restrictions in preventing infectious complications in cancer patients. Studies evaluating various approaches to diet restrictions have not shown clear benefit.

A meta-analysis and a systematic review of articles evaluating the effect of a neutropenic diet on infection and mortality rates in cancer patients found no superiority or advantage in using a neutropenic diet over a regular diet in neutropenic cancer patients.[1,2] Four studies were identified in the meta-analysis, one observational study and three randomized controlled trials, including 918 patients with cancer or stem cell transplant. Even after the observational study was omitted from the analysis, the results persisted.[1] The systematic review identified only three randomized controlled trials,[3,4,5] which compared different diets in 192 children and adults. The review concluded that these individual studies provided no evidence showing that the use of a low-bacterial diet prevents infections.[2]

Other studies have demonstrated potential adverse effects of neutropenic diets. One group of investigators [6] conducted a retrospective review of 726 patients who had undergone hematopoietic cell transplantation (HCT). The 363 patients who received the neutropenic diet experienced significantly more documented infections than did the 363 patients receiving the general hospital diet, which permitted black pepper and well-washed fruits and vegetables and excluded raw tomatoes, seeds, and nuts. The difference in infection rates was especially evident after the resolution of neutropenia (P < .008). The neutropenic diet group had a significantly higher rate of infections that could be attributed to a gastrointestinal source, as well as a trend toward a higher rate of vancomycin-resistant enterococci infections.[6]

Without clinical evidence to define the dietary restrictions required to prevent foodborne infection in immunocompromised cancer patients, recommendations for food safety are based on general food safety guidelines and the avoidance of foods most likely to contain pathogenic organisms. The effectiveness of these guidelines depends on patient and caregiver knowledge about, and adherence to, safe food handling practices and avoidance of higher-risk foods. Leading cancer centers provide guidelines for HCT patients and information about food safety practices related to food purchase, storage, and preparation (e.g., the University of Pittsburgh Medical Center's ​Stem Cell Transplant Diet and Memorial Sloan Kettering Cancer Center's Neutropenic Diet). Patients can be referred to FoodSafety.gov for up-to-date information about food recalls and alerts.

Recommendations support the use of safe food-handling procedures and avoiding consumption of foods that pose a high risk of infection, as noted in Table 7.

References:

1. Sonbol MB, Firwana B, Diab M, et al.: The Effect of a Neutropenic Diet on Infection and Mortality Rates in Cancer Patients: A Meta-Analysis. Nutr Cancer 67 (8): 1230-8, 2015.
2. van Dalen EC, Mank A, Leclercq E, et al.: Low bacterial diet versus control diet to prevent infection in cancer patients treated with chemotherapy causing episodes of neutropenia. Cochrane Database Syst Rev (9): CD006247, 2012.
3. van Tiel F, Harbers MM, Terporten PH, et al.: Normal hospital and low-bacterial diet in patients with cytopenia after intensive chemotherapy for hematological malignancy: a study of safety. Ann Oncol 18 (6): 1080-4, 2007.
4. Moody K, Finlay J, Mancuso C, et al.: Feasibility and safety of a pilot randomized trial of infection rate: neutropenic diet versus standard food safety guidelines. J Pediatr Hematol Oncol 28 (3): 126-33, 2006.
5. Gardner A, Mattiuzzi G, Faderl S, et al.: Randomized comparison of cooked and noncooked diets in patients undergoing remission induction therapy for acute myeloid leukemia. J Clin Oncol 26 (35): 5684-8, 2008.
6. Trifilio S, Helenowski I, Giel M, et al.: Questioning the role of a neutropenic diet following hematopoetic stem cell transplantation. Biol Blood Marrow Transplant 18 (9): 1385-90, 2012.
7. Tomblyn M, Chiller T, Einsele H, et al.: Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 15 (10): 1143-238, 2009.
8. Lund BM: Microbiological food safety and a low-microbial diet to protect vulnerable people. Foodborne Pathog Dis 11 (6): 413-24, 2014.

Nutrition Trends in Cancer

Special Diets

Maintaining adequate nutrition while undergoing treatment for cancer is imperative because it can reduce treatment-related side effects, prevent delays in treatment, and help maintain quality of life.[1] However, many patients view their diet as a way to enhance treatment effectiveness, minimize treatment-related toxicities, or target the cancer itself, often by following a specific diet with supposed cancer-fighting benefits or by taking dietary supplements. Patients are likely to search the internet and other lay sources of information for dietary approaches to manage cancer risk and to improve prognosis. Unfortunately, much of this information is not supported by a sufficient evidence base.

The sections below summarize the state of the science on some of the most popular diets and dietary supplements.

Vegetarian or vegan diet

A vegetarian diet is popular, is easy to implement, and, if followed carefully, does not result in nutritional deficiencies. There is strong evidence that a vegetarian diet reduces the incidence of many types of cancer, especially cancers of the gastrointestinal (GI) tract.[2] However, it is unknown how following a vegetarian or vegan diet can affect treatment-induced symptoms, cancer therapies, or outcomes for someone undergoing cancer therapy. There are no published clinical trials, pilot studies, or case reports on the effectiveness of a vegetarian diet for the management of cancer therapy and symptoms. There is no evidence suggesting a benefit of adopting a vegetarian or vegan diet upon diagnosis or while undergoing cancer therapy. On the other hand, there is no evidence that an individual who follows a vegetarian or vegan diet before cancer therapy should abandon it upon starting treatment.

The Men's Eating and Living (MEAL) Study (CALGB 70807 [Alliance]) was a randomized trial of men with early-stage prostate cancer. It compared participants who were managed with active surveillance and behavioral counseling with a control group who received no counseling.[3][Level of evidence: I] The study found that the intervention to increase vegetable intake was successful—there was a statistically significant increase in consumption. However, time to cancer progression did not differ between the two groups.

Macrobiotic diet

A macrobiotic diet varies according to a person's sex, their level of activity, and the climate (and season) where they live, among other variables. It is a high-carbohydrate, low-fat, plant-based diet stemming from philosophical principles promoting a healthy way of living. The diet consists of 35% to 50% (by weight) whole grains, 25% to 35% vegetables, 5% to 10% soup, 5% to 10% cooked vegetables and sea vegetables, and 5% to 10% fish.

Although there are anecdotal reports of the effectiveness of a macrobiotic diet as an alternative cancer therapy, none has been published in peer-reviewed, scientific journals. No clinical trials, observational studies, or pilot studies have examined the diet as a complementary or alternative therapy for cancer. In fact, two reviews of the diet concluded that there is no scientific evidence for the use of a macrobiotic diet in cancer treatment.[4,5] Because the current research is severely lacking, recommendations for or against the diet in conjunction with standard cancer treatment cannot be made. No current clinical trials are studying the role of the macrobiotic diet in cancer therapy.

Ketogenic diet

A ketogenic diet has been well established as an effective alternative treatment for some cases of epilepsy and has gained popularity for use in conjunction with standard treatments for glioblastoma. The theory behind the diet as cancer treatment is that reducing glucose availability to a tumor can reduce tumor activity, and that this reduction can be achieved through entering a state of ketosis via the ketogenic diet's increased fat intake and restriction of carbohydrates.

The ketogenic diet can be difficult to follow and relies more on exact proportions of macronutrients (typically a 4:1 ratio of fat to carbohydrates and protein) than other complementary and alternative medicine (CAM) diets.

Most studies have focused on the diet's feasibility, tolerability, and safety, all of which have been shown for patients with glioblastoma at various stages of the disease.[6,7,8] Because safety and feasibility have been proven, several trials are recruiting patients to study the effectiveness of the ketogenic diet on glioblastoma. Therefore, it is safe for a patient diagnosed with glioblastoma to start a ketogenic diet if implemented properly and under the guidance of a registered dietitian.[9] However, effectiveness for symptom and disease management remains unknown.

Similarly, findings from a study that compared the acceptability and adverse effects of a ketogenic diet to the American Cancer Society's high-fiber, low-fat diet among women with ovarian or endometrial cancer found no differences between groups over 12 weeks. Further, the findings indicated that the ketogenic diet was both safe and acceptable.[10] The effectiveness for symptom and disease management for ovarian or endometrial cancer also remains unknown.

Dietary Supplements

Vitamin C

For information about the use of intravenous vitamin C as a treatment for people with cancer, see Intravenous Vitamin C.

Probiotics

The use of probiotics has become prevalent within and outside of cancer therapy. Strong research has shown that probiotic supplementation during radiation therapy, chemotherapy, or both is well tolerated and can help prevent radiation- and chemotherapy-induced diarrhea, especially in those receiving radiation to the abdomen.[11,12,13] If a patient is undergoing radiation to the abdomen or receiving a chemotherapy agent with diarrhea as a common side effect, starting a probiotic supplement upon initiation of therapy could be beneficial. Evidence is also emerging for possible benefits of probiotics for immunotherapy-induced toxicities, particularly in the colon.[14]

Melatonin

Melatonin is a hormone produced endogenously that has been used as a CAM supplement (along with chemotherapy or radiation therapy) for targeting tumor activity and for reducing treatment-related symptoms, primarily for solid tumors.

Several studies have shown tumor response to, or disease control with, chemotherapy alongside oral melatonin, as opposed to chemotherapy alone. One study has shown tumor response with melatonin in conjunction with radiation therapy.[15,16,17,18,19,20] The combination of melatonin and chemotherapy may, in fact, increase survival time by up to 5 years compared with chemotherapy alone. However, another study did not demonstrate increased survival with melatonin, but did demonstrate improved quality of life.[21]

Melatonin taken in conjunction with chemotherapy may help reduce or prevent some treatment-related side effects and toxicities that can delay treatment, reduce doses, and negatively affect quality of life. Melatonin supplementation has been associated with significant reductions in neuropathy and neurotoxicity, myelosuppression, thrombocytopenia, cardiotoxicity, stomatitis, asthenia, and malaise.[16,17,19,22] However, one study found no benefit in taking supplemental melatonin for reducing toxicities or improving quality of life.[23]

Overall, several small studies show some evidence supporting melatonin supplementation alongside chemotherapy, radiation therapy, or both for solid tumor treatment, aiding tumor response, and reducing toxicities. Negative side effects for melatonin supplementation have not been found. Therefore, it may be appropriate to provide oral melatonin in conjunction with chemotherapy or radiation therapy to a patient with an advanced solid tumor.

Oral glutamine

Glutamine is an amino acid that is especially important for GI mucosal cells and their replication. Chemotherapy and radiation therapy often damage these cells, causing mucositis and diarrhea, which can lead to treatment delays and dose reductions and severely affect quality of life. Some evidence suggests that oral glutamine can reduce both of those toxicities by aiding in faster healing of the mucosal cells and entire GI tract.

For patients receiving chemotherapy who are at high risk of developing mucositis, either because of previous mucositis or having received known mucositis-causing chemotherapy, oral glutamine may reduce the severity and incidence of mucositis.[24,25,26]

For patients receiving radiation therapy to the abdomen, oral glutamine may reduce the severity of diarrhea and can lead to fewer treatment delays.[27,28] However, one study found no benefit to oral glutamine for preventing chemotherapy-related diarrhea.[29]

In addition to reducing GI toxicities, oral glutamine may also reduce peripheral neuropathy in patients receiving the chemotherapy agent paclitaxel.[30] Larger randomized controlled trials are needed to further determine the effectiveness of oral glutamine in treating peripheral neuropathy.

Oral glutamine is a safe, simple, and relatively low-cost supplement that may reduce severe chemotherapy- and radiation-induced toxicities.

References:

1. Lis CG, Gupta D, Lammersfeld CA, et al.: Role of nutritional status in predicting quality of life outcomes in cancer--a systematic review of the epidemiological literature. Nutr J 11: 27, 2012.
2. Tantamango-Bartley Y, Jaceldo-Siegl K, Fan J, et al.: Vegetarian diets and the incidence of cancer in a low-risk population. Cancer Epidemiol Biomarkers Prev 22 (2): 286-94, 2013.
3. Parsons JK, Zahrieh D, Mohler JL, et al.: Effect of a Behavioral Intervention to Increase Vegetable Consumption on Cancer Progression Among Men With Early-Stage Prostate Cancer: The MEAL Randomized Clinical Trial. JAMA 323 (2): 140-148, 2020.
4. Lerman RH: The macrobiotic diet in chronic disease. Nutr Clin Pract 25 (6): 621-6, 2010.
5. Kushi LH, Cunningham JE, Hebert JR, et al.: The macrobiotic diet in cancer. J Nutr 131 (11 Suppl): 3056S-64S, 2001.
6. Rieger J, Bähr O, Maurer GD, et al.: ERGO: a pilot study of ketogenic diet in recurrent glioblastoma. Int J Oncol 44 (6): 1843-52, 2014.
7. Champ CE, Palmer JD, Volek JS, et al.: Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. J Neurooncol 117 (1): 125-31, 2014.
8. Schmidt M, Pfetzer N, Schwab M, et al.: Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial. Nutr Metab (Lond) 8 (1): 54, 2011.
9. Kossoff EH, Zupec-Kania BA, Amark PE, et al.: Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group. Epilepsia 50 (2): 304-17, 2009.
10. Cohen CW, Fontaine KR, Arend RC, et al.: A Ketogenic Diet Is Acceptable in Women with Ovarian and Endometrial Cancer and Has No Adverse Effects on Blood Lipids: A Randomized, Controlled Trial. Nutr Cancer 72 (4): 584-594, 2020.
11. Delia P, Sansotta G, Donato V, et al.: Use of probiotics for prevention of radiation-induced diarrhea. World J Gastroenterol 13 (6): 912-5, 2007.
12. Chitapanarux I, Chitapanarux T, Traisathit P, et al.: Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients. Radiat Oncol 5: 31, 2010.
13. Osterlund P, Ruotsalainen T, Korpela R, et al.: Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: a randomised study. Br J Cancer 97 (8): 1028-34, 2007.
14. Badgeley A, Anwar H, Modi K, et al.: Effect of probiotics and gut microbiota on anti-cancer drugs: Mechanistic perspectives. Biochim Biophys Acta Rev Cancer 1875 (1): 188494, 2021.
15. Cerea G, Vaghi M, Ardizzoia A, et al.: Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versus irinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations. Anticancer Res 23 (2C): 1951-4, 2003 Mar-Apr.
16. Lissoni P, Barni S, Mandalà M, et al.: Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 35 (12): 1688-92, 1999.
17. Lissoni P, Chilelli M, Villa S, et al.: Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial. J Pineal Res 35 (1): 12-5, 2003.
18. Lissoni P, Meregalli S, Nosetto L, et al.: Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology 53 (1): 43-6, 1996 Jan-Feb.
19. Lissoni P, Paolorossi F, Ardizzoia A, et al.: A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. J Pineal Res 23 (1): 15-9, 1997.
20. Lissoni P, Paolorossi F, Tancini G, et al.: A phase II study of tamoxifen plus melatonin in metastatic solid tumour patients. Br J Cancer 74 (9): 1466-8, 1996.
21. Sookprasert A, Johns NP, Phunmanee A, et al.: Melatonin in patients with cancer receiving chemotherapy: a randomized, double-blind, placebo-controlled trial. Anticancer Res 34 (12): 7327-37, 2014.
22. Lissoni P, Tancini G, Barni S, et al.: Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin. Support Care Cancer 5 (2): 126-9, 1997.
23. Del Fabbro E, Dev R, Hui D, et al.: Effects of melatonin on appetite and other symptoms in patients with advanced cancer and cachexia: a double-blind placebo-controlled trial. J Clin Oncol 31 (10): 1271-6, 2013.
24. Anderson PM, Schroeder G, Skubitz KM: Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 83 (7): 1433-9, 1998.
25. Skubitz KM, Anderson PM: Oral glutamine to prevent chemotherapy induced stomatitis: a pilot study. J Lab Clin Med 127 (2): 223-8, 1996.
26. Peterson DE, Jones JB, Petit RG: Randomized, placebo-controlled trial of Saforis for prevention and treatment of oral mucositis in breast cancer patients receiving anthracycline-based chemotherapy. Cancer 109 (2): 322-31, 2007.
27. Kucuktulu E, Guner A, Kahraman I, et al.: The protective effects of glutamine on radiation-induced diarrhea. Support Care Cancer 21 (4): 1071-5, 2013.
28. Rotovnik Kozjek N, Kompan L, Soeters P, et al.: Oral glutamine supplementation during preoperative radiochemotherapy in patients with rectal cancer: a randomised double blinded, placebo controlled pilot study. Clin Nutr 30 (5): 567-70, 2011.
29. Bozzetti F, Biganzoli L, Gavazzi C, et al.: Glutamine supplementation in cancer patients receiving chemotherapy: a double-blind randomized study. Nutrition 13 (7-8): 748-51, 1997 Jul-Aug.
30. Vahdat L, Papadopoulos K, Lange D, et al.: Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res 7 (5): 1192-7, 2001.

Latest Updates to This Summary (11 / 16 / 23)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Nutrition Therapy

Added text about a Cochrane review of 38 trials involving 4,304 patients that reported on the use of megestrol at doses of 160 to 800 mg per day for treatment of cachexia-anorexia syndrome (CAS) (cited Ruiz-Garcia et al. as reference 65).

Added text about a 2022 meta-analysis of eight trials, which found that megestrol acetate did not provide symptomatic improvement of anorexia/cachexia in patients with advanced cancer (cited Lim et al. as reference 69).

Added Olanzapine as a new subsection.

Revised Table 6 to add information about whether commonly prescribed medications for CAS affect appetite, cachexia, or both.

This summary is written and maintained by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about nutrition before, during, and after cancer treatment. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Nutrition in Cancer Care are:

• Marilyn J. Hammer, PhD, DC, RN, FAAN (Dana-Farber Cancer Institute)
• Jared R. Lowe, MD, HMDC (University of North Carolina School of Medicine)
• Kristina B. Newport, MD, FAAHPM, HMDC (Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center)
• Maria Petzel, RD, CSO, LD, CNSC, FAND (University of TX MD Anderson Cancer Center)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Supportive and Palliative Care Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."

The preferred citation for this PDQ summary is:

PDQ® Supportive and Palliative Care Editorial Board. PDQ Nutrition in Cancer Care. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/side-effects/appetite-loss/nutrition-hp-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389293]

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us.

Last Revised: 2023-11-16