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."
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. 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. 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. 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. 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 adenosine(Drug information on adenosine) triphosphate and mixtures of amino acids 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, and statins, remain to be studied in a cancer clinical trial setting; a small study on macrolide antibiotics has been published.
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.