Nutrition as an Integral Component of Supportive Care

February 1, 2003

Palliative care, previously viewed by many as anend-of-life movement, is now recognized as anapproach whose principles should infuse the care ofall patients with a chronic illness throughout the fullcourse of that illness. For example, the World HealthOrganization (WHO) has redefined palliative care asfollows:

Palliative care, previously viewed by many as an end-of-life movement, is now recognized as an approach whose principles should infuse the care of all patients with a chronic illness throughout the full course of that illness. For example, the World Health Organization (WHO) has redefined palliative care as follows:

"Palliative care is an approach which improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual."[1]

Therefore, palliative/supportive care should now be regarded as an exercise in prevention-prevention of human suffering through early diagnosis and appropriate treatment of nutritional problems and other symptoms which contribute to patient-family distress.[ 2]

While the WHO model for palliative care is logical and compelling, it has not been adopted in a tangible fashion by those responsible for the care of cancer patients. The emphasis remains on offering patients sequential therapies. At the time of diagnosis, chemotherapy, radiotherapy, and surgery may be employed but only later in the course of illness may emphasis be placed on symptom management.

Symptoms: Role in Disease Progression

The argument for improving patient quality of life through ensuring symptom control at all stages of illness is unassailable. However, there are also sound biologic reasons for instituting palliative care earlier. For example, the plasticity of the nervous system is such that unrelieved pain results in a change in the transmission of the pain message with the recruitment of previously silent pathways, the enhancement of neurotransmitter activity conducting the pain message, and the development of a general state of hyperexcitability.[3] Thus pain not relieved may become pain difficult to relieve.

Aside from neurologic changes, chronic pain is associated with many systemic alterations, including activation of cytokine production, alterations in autonomic nervous system function, and increase in depression and anxiety, coupled with changes in the hypothalamic pituitary axis. Thus, pain is not simply a "hard-wired" problem occurring in parallel with cancer-rather it excites systemic changes that may influence the overall course of the cancer. At the animal level, research has demonstrated that acute pain can increase tumor growth, and that control of pain correlates with improved survival.[4,5]

Pain and other symptoms common to cancer patients should be regarded as life-saving responses to acute threat or injury which cause great harm when the stress reaction "switch" is left on over time. While necessary when the body must respond to an acute stress, patterns of cytokine production and neuralhumoral alterations associated with the chronic inflammatory response induced by cancer do not protect the body from cancer progress; rather, induced symptoms cause suffering and may actually enhance tumor progress.[6] Therefore, in the interest of offering both humane care and care that may prolong the patient's life, it is imperative that excellent symptom management be provided for patients at the earliest possible moment.

The Anorexia-Cachexia Syndrome

The anorexia-cachexia syndrome is an example of this principle. Similar to pain, cancer patients exhibiting loss of appetite and wasting not related to secondary causes (eg, mood change, pain, infection, bowel obstruction, etc) often exhibit an aberrant systemic response characterized by production of a variety of cytokines (the critical ones related to anorexia and cachexia include tumor necrosis factor, interleukin [IL]-1, and IL-6) increased catecholamine activity, hypermetabolism, gluconeogenesis, and alterations in fatty acid metabolism.[7] A chaotic immune response to the tumor is evident, and the "chemical stew" surrounding the tumor contains factors that may enhance tumor growth and tumorinduced weight loss. These metabolic aberrations may result in profound cachexia, contributing to poor response to treatment, increased adverse therapeutic events, loss of strength, function and ultimately death. Similar mechanisms appear to be present in other wasting disorders such as advanced congestive heart failure and chronic obstructive pulmonary disease.[8,9]

Cancer Nutrition: Rehabilitation Programs

Taking advanced non-small cell lung cancer as an example, many patients present with evidence of weight loss. These patients form a subset who respond poorly to therapy.[10] Logically, programs should be in place for them with the following characteristics:

• Using simple assessment scales (such as the Edmonton Symptom Assessment Scale and the PGSGA Nutritional Assessment System) the patient's symptom profile and nutritional status is established.[ 11,12]

• Symptoms are vigorously assessed and treated. With respect to nutrition, if weight loss, appetite change, or wasting are apparent, patients are offered nutritional counseling, encouraged to take part in a rehabilitation program geared to their needs (if muscles are not used, they will waste), and nutraceuticalpharmacologic interventions are considered.

• Follow-up visits stress not only cancer chemotherapy and tumor volume considerations, but also symptom control, status, weight change, and patient function.

Promising Lines of Research

To the present time, clinicians may have been discouraged from including nutritional considerations as a major part of their therapeutic approach as results with existing therapies have been modest. For example, corticosteroids can enhance appetite, but are fundamentally catabolic agents. Progestational agents also increase appetite and weight, but the weight gained is primarily fat and not lean body mass. Cannabinoids may increase appetite under certain circumstances, but again without change in lean body mass. Standard enteral and parenteral nutritional support of patients with advanced illness may stabilize weight for a period without evident improvement in survival. The costs and adverse effects of nutritional support are major concerns.

Today, however, evidence exists that a number of compounds may alter the above discouraging picture as their use may be associated with improvement in lean body mass and function. For example, omega-3 fatty acids may have these qualities. Studies on these agents in animals have usually shown that they reduce cancer growth[13-15] while increasing the efficacy and reducing the adverse effects of a variety of chemotherapeutic agents.[16,17]

Reflecting the lack of research on palliative care issues, a steep "voltage drop" exists between the laboratory and the clinical research arena. Several human studies on omega-3 fatty acids, however, are positive for maintenance of lean body mass.[18,19] Evidence of improvement in patient survival has not been demonstrated in randomized trials. Studies of omega-3 use in human populations in combination with chemotherapy are yet to be carried out.

More recently, a few studies involving the use of anabolic agents[20] adenosine triphosphate[21] and mixtures of amino acids[22] provide evidence that they also may be associated with improvements in lean body mass and/or function. Many other compounds in common use that interfere with the cytokine inflammatory cascade, such as angiotensinconverting enzyme (ACE) inhibitors,[23] and statins,[24] remain to be studied in a cancer clinical trial setting; a small study on macrolide antibiotics has been published.[25]

Conclusions

The author believes that we are faced with an ethical dilemma-there is sufficient evidence that nutritional interventions should be studied at the onset of illness in concert with other anticancer approaches. How do we do this when the single-track approach of much cancer chemotherapy research today excludes the opportunity to adopt this approach? For example, the exclusion criteria for chemotherapy trials usually exclude the opportunity for patients to take part in clinical research trials on nutritional agents at the same time. An overhaul of our current clinical trial approach is clearly required.

In summary, the team approach to cancer management- with dietitians and nutritional experts as a part of that team-is clearly in order. Nutritional gains are difficult when patients are severely wasted. Conversely, applying our skills when patients first begin to lose weight and encouraging and allowing them to take part in clinical trials of new promising agents when combined with rehabilitation offers a logical approach to modern cancer patient care.

Discussion

Editor's Note: All workshop participants contributed to this discussion, highlights of which are presented here.

Funding Hospice: Limitations and Capitation

Maria Steinbaugh and Costantino Benedetti pointed out that the hospice movement started as a reaction to medical overtreatment of patients at the end of life. The hospice movement was initially funded by private donations. In 1983, Medicare began to provide hospice benefits but limited those benefits to the last 6 months of life and capitated reimbursement at approximately $100 a day. These limitations force a focus on end-oflife care rather than on supportive care throughout the course of a patient's disease.

Reducing Care Costs Through Early Initiation of Supportive Care

Neil MacDonald suggested that public policymakers might be convinced to change hospice benefit limitations if they were made aware of the biologic argument for supportive care. The biologic argument is that supportive care promotes quality of life, and helps control symptoms, such as anorexia-cachexia, that cause loss of function and independence. Care costs are thereby reduced. A health economist could help provide compelling financial data to public policy-makers. Discussants agreed that patients currently use hospice care only during the last week or two of life. Ideally, initiating supportive care at diagnosis would ensure good nutrition support and symptom control, reducing hospital or long-term care admissions, improving quality of life, and controlling costs. Douglas Heimburger concluded that physicians are already reimbursed for seeing patients for palliative and supportive care, but the medical community should recognize the need for and value of early initiation of supportive care.

Changing Negative Perceptions of Hospice

Dr. Benedetti expressed concern that hospice care does not allow for some forms of treatment that can be beneficial to patients. Because of hospice reimbursement limitations, for instance, coverage is lacking for blood transfusions for a hospice patient with severe anemia and for palliative chemotherapy and/or radiation therapy for patients who could benefit. Patients, family caregivers, and society perceive that admission to hospice signals the end of life. Changing the terminology from hospice to palliative medicine or to supportive care may shift public perception.

Providing Continuity of Care With an Interdisciplinary Supportive Care Team

Molly Loney pointed out that delivery of care is fragmented. Patients move from acute care to palliative care with no planned transition. Ideally, supportive care would start at diagnosis. Patients would be followed throughout the continuum of care by an interdisciplinary supportive care team that would include physicians, dietitians, nurses, social workers, psychologists, pharmacists, and physical/occupational therapists. Dr. MacDonald reported that members of his interdisciplinary team were initially concerned that patients would view rehabilitation and nutrition care as less important than other interventions. However, patients and family understood and valued the role of interventions such as nutrition and exercise. Abby Bloch pointed out that, in reality, the costs of extensive supportive care programs may be prohibitive and that care teams rarely have dietitians dedicated to them.

Using Volunteers and Donated Funds in Supportive Care

Discussants reported several experiences in which philanthropy and volunteerism helped support hospice and supportive care programs. A donation from a grateful family enabled Dr. MacDonald to hire a dietitian. Charlette Gallagher- Allred has volunteered in hospice programs for more than 25 years. In her experience, 95% of patients and families ask to see a dietitian for nutrition intervention when dietitian services are offered because food and mealtime interactions are meaningful in their lives.

Using Food in the Care of Terminally Ill Patients

Dr. Gallagher-Allred listed the following ways she has seen terminally ill patients or their families use food:

To accelerate death. Sometimes patients will ask if certain foods could hasten death, for example, a high-potassium diet with chronic renal failure and discontinuation of dialysis.

• To prolong life. This is palliative nutrition intervention, for example, the patient who wants to live long enough to experience a significant family event, such as a graduation or wedding.

• To prolong death. Families of comatose patients in nursing homes may use this approach. In these cases nutrition intervention does not promote quality of life but delays death.

• To control others. Patients may refuse to eat to get their way with nursing staff or caregivers.

Dr. MacDonald reported results from a qualitative study showing that some people use food as a means of enhancing communication and contact. Many discussants reported cases in which palliative tube feeding was used to prolong life to reach an important milestone, and cases in which eating promoted socializing and enjoyment of mealtime with friends and families.

Disclosures:

The author(s) have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. World Health Organization: Pain relief and palliative care, in National Cancer Control Programme. Policies and Managerial Guidelines, 2nd ed. Geneva, World Health Organization, 2002.
2. MacDonald N: Palliative care-The fourth phase of cancer prevention. Cancer Detect Prev 15:3253-3255, 1991.
3. Coderre TJ, Katz J, Baccarino AL, et al: Contribution of central neuroplasticity to pathological pain: Review of clinical and experimental evidence. Pain 52:259-285, 1993.
4. Liebeskind J: Pain can kill. Pain 44:3-4, 1991
5. Page GG, McDonald JS, Ben-Eliyahu S: Pre-operative versus postoperative administration of morphine: Impact on the neuro-endocrine, behavioural and metastatic-enhancing effects of surgery. Br J Anaesth 81:216-223, 1998.
6. Balkwill F, Mantovani A: Inflammation and cancer: Back to Virchow? Lancet 357:539-545, 2001.
7. Tisdale M: Cancer cachexia. J Natl Cancer Inst 89:1763-1773, 1997.
8. Schols AMWJ, Wouters EFM: Nutritional abnormalities and supplementation in chronic obstructive pulmonary disease. Clin Chest Med 21(4):753-763, 2000.
9. Anker SD, Ponikowski P, Varney S, et al: Wasting as independent risk factor for mortality in chronic heart failure. Lancet 349:1050-1053, 1997.
10. Scott HR, McMillan DC, Forrest LM, et al: The systemic inflammatory response, weight loss, performance status and survival in patients with inoperable non-small cell lung cancer. Br J Cancer 87:264-267, 2002.
11. www.palliative.org
12. McMahon K, Decker G, Ottery FD: Integrating procative nutritional assessment in clinical practices to prevent complications and cost. Semin Oncol 25(2):20-27, 1998.
13. Borgeson CE, Pardini L, Pardini RS, et al: Effects of dietary fish oil on human mammary carcinoma and on lipid metabolizing enzymes. Lipids 24:290-295, 1989.
14. Tisdale MJ, Beck SA, Hudson EA: Effects of eicosapentaenoic acid on tumour growth and cachexia in mouse colon cancer. World Rev Nutr Diet 76:86-88, 1994.
15. Rose DP, Connolly JM: Effects of dietary omega-3 fatty acids on human breast cancer growth and metastases in nude mice. J Natl Cancer Inst 85:1743-1747, 1993.
16. Hardmann WE, Moyer MP, Cameron IL: Fish oil supplementation enhanced CPT-11 (ironotecan) efficacy against MCF7 breast carcinoma xenografts and ameliorated intestinal side-effects. Br J Cancer 81(3):440- 448, 1999.
17. Shao Y, Pardini L, Pardini RS: Intervention of transplantable human mammary carcinoma MX-1 chemotherapy with dietary menhaden oil in athymic mice: Increased therapeutic effects and decreased toxicity of cyclophosphamide. Nutr Cancer 28(1):63-73, 1997.
18. Barber MD, Ross JA, Voss AC, et al: An oral nutritional supplement enriched with fish oil reverses weight loss in patients with pancreatic cancer. Br J Cancer 81(1):80-86, 1999.
19. Fearon KCH, von Meyenfeldt MF, Moses AGW, et al, on behalf of the Cancer Cachexia Study Group: An energy and protein dense, high n- 3 fatty acid oral supplement promotes weight gain in cancer cachexia. Eur J Cancer 37(6):S27-S28, 2001.
20. Von Roenn JH, Tchekmedyian S, Sheng KN, et al: Oxandrolone in cancer-related weight loss (WL): Improvement in weight, body cell mass (BCM), performance status and quality of life (QOL). Proc Am Soc Clin Oncol 21:1450, 2002.
21. Agteresch HJ, Rietveld T, Kerkhofs LGM, et al: Beneficial effects of adenosine triphosphate on nutritional status in advanced lung cancer patients: A randomized clinical trial. J Clin Oncol 20(2):371-378, 2002.
22. May PE, Barber A, D’Olimpio JT, et al: Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxybeta- methlybutyrate, arginine, and glutamine. Am J Surg 183:471-479, 2002.
23. Onder G, Penninx BW, Balkrishnan R, et al: Relation between the use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: An observational study. Lancet 359:926-930, 2002.
24. Yeung AC, Tsao P: Statin therapy-Beyond cholesterol lowering and anti-inflammatory effects. Circulation 105:2937-2938, 2002.
25. Sakamoto M, Mikasa K, Majima T, et al: Anti-cachectic effect of clarithromycin for patients with unresectable non-small cell lung cancer. Chemotherapy 47:444-451, 2001.