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Cachexia-Anorexia-Asthenia
Vol. l ONo. 2 Februmy 1995
Journal of Pain and Symptom Management 151
Cachexia-Anorexia-Asthenia Neil M a c D o n a l d , MD, H. R i c h a r d A l e x a n d e r , MD, a n d E d u a r d o Bruera, MD Centerfor Bioethics (N.M.), Clinical Research Institute of Montreal, Montreal, Quebec; and Edmonton General Hospital (E.B), Edmonton, Alberta, Canada; and Surgery Branch (H.R.A.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland
Abstract The National Cancer Institute (Canada) sponsored a workshop on symptom control in Banff Alberta, in October 1993. This article reports on the workshop recommendations for research on one symptom complex, the cachexia-anorexia-asthenia syndrome. In addition to encouraging stud), generation, the recommendations provide a baseline for assessing the scope and strength of future Canadian research initiatives on cachexia-anorexia-asthenia. J Pain Symptom Manage 1995;10:151-155.
Key Words Cachexia, anorexia, research workshop
Introduction Weight loss, asthenia, and anorexia, often associated with chronic nausea, are a m o n g the most c o m m o n symptom problems afflicting patients with advanced cancer, l Earlier, prec h e m o t h e r a p y studies suggest that weight loss and associated metabolic abnormalities may account for 25% of cancer deaths9 As patients with cachexia-anorexia are often weak and unable to care for themselves, family resources are severely taxed, and patients often require institutional care for p r o l o n g e d periods prior to death. T h e term " c a c h e x i a - a n o r e x i a s y n d r o m e " is used somewhat loosely, as the defining qualities of the syndrome and the c o n s e q u e n t tests that m o n i t o r progress or regression remain imprecise. T h e r e is a Chinese proverb that states " T h e beginning of wisdom is to call things by
Address reprint requests to: Neil MacDonald, MD, Center for Bioethics, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, H2Q 1R7 Canada. Acceptedfcrr publication:June 20, 1994. © U.S. Cancer Pain Relief Committee, 1995 Published by Elsevier, NewYork, NewYork
their right names. '''4 A m o d e r n coiner of aphorisms, Sir Peter Medawar has said, " N o new truth will declare itself f r o m inside a h e a p of facts. '':~ At present, a " h e a p of facts" g a r n e r e d by research workers working in disparate areas is available to the clinical investigator c o n c e r n e d with cancer cachexia. T h e web c o n n e c t i n g these observations in a c o h e r e n t mosaic, however, remains to be fully woven. Some salient features stand out, however, including 1. T h e cachexia-anorexia complex has a variable incidence d e p e n d i n g on the type of primary tumor. 4 It is relatively u n c o m m o n in patients with one f o r m of a d e n o c a r c i n o m a , breast cancer, while it is very c o m m o n in certain o t h e r forms of a d e n o c a r c i n o m a such as lung cancer and pancreatic cancer. Wasting is not c o m m o n l y observed in the hematologic malignancies although myelodysplastic syndromes are often associated with e x t r e m e wasting. 2. Studies c o m p a r i n g the biology of those tumors that show a propensity to develop c a c h e x i a - a n o r e x i a with those that do not, remain to be carried out. T h e syndrome is 0885-3924/95/$9.50 SSDI 0885-3924(94)00077-X
152
MacDonald et al.
probably caused by chemical factors produced as a result of a host response or directly by the tumor. A n u m b e r of cytokines that can produce symptoms mimicking the cachexia-anorexia syndrome have been identified. The list includes t u m o r necrosis factor, interleukins 1 and 6, and interferon 7. However, specific cytokine abnormalities 5-8 have not been linked to cancer cachexia-anorexia in humans, and noncytokine chemical factors have also been implicated. 'j We presume that an interactive cascade involving multiple chemical factors is responsible. 3. Metabolic abnormalities may precede weight loss in animal cachexia-anorexia tumor models, I° and it is presumed that the same p h e n o m e n a occur in humans. While subsequent decrease in nutrient intake will compound the problem, loss of appetite appears to be related to the onset of these metabolic abnormalities, rather than acting as a primary cause of the cachexia-anorexia syndrome. 4. Clinicians must be careful to diagnose those situations where cancer patients lose weight because of simple starvation, potentially corrected with parenteral or enteral nutrition, rather that assigning all changes in weight to the cachexia-anorexia syndrome. Correctable examples include some patients with head and neck cancer with obstruction of the upper digestive tract, and some patients with ovarian carcinoma with intermittent small-bowel obstruction. Notwithstanding the occasional patient who is truly starving, the vast majority of cancer patients who lose weight suffer from a complex metabolic aberration that does not respond to simple replacement of nutrients. A n u m b e r of studies have demonstrated that replacement of calories using standard enteral or parenteral diets does not result in meaningful weight gain or improvement in quality of life or tumor response. II It remains to be d e t e r m i n e d whether the use of special dietary supplements directed at correction of specific metabolic abnormalities will change the current wisdom that dietary supplementation does not help patients with the cachexia-anorexia syndrome. 5. Similar to the observations made with diet, drug trials attempting to increase appetite and weight generally have not been successful. Corticosteroids certainly produce an immediate improvement in appetite and occasionally
Vol. 10 No. 2 February 1995
in weight, but the effect is usually short-lived. 12 However, the observation that progestational agents can improve appetite and reverse weight loss is possibly of major importance. It remains to be clearly d e t e r m i n e d whether the immediate improvement in patient well-being produced by progestational agents translates into longer-term improvements in patient energy, mobility, and independence. However, for the first time pharmacologic therapy has significantly impacted upon the cachexia-anorexia syndrome, thus creating the impetus to "work back" from the clinical observation to the laboratory to determine how these agents work. Consequent understanding of an exploitable lead may result in development of more specific agents. The use of progestational agents in combination with other drugs that are relatively ineffective when used alone or with special diets may offer a promising area for future study. The McMaster Loop 1`~ (Figure 1) provides a useful framework for assessing the importance and feasibility of a research initiative. The cachexia-anorexia complex certainly presents an extraordinary b u r d e n for involved patients, families, and society. While its pathophysiology remains to be fully elucidated, sufficient information is available to frame studies linking the laboratory and the bedside. Successful pharmacologic intervention with progestational agents provides a base for immediate projection of further clinical interventions, which could be carried out at reasonable cost and with reasonable anticipation of success. This success could be measured both in terms of alleviating suffering and reducing health-care costs. The lessons learned from these studies, in turn, will lead to more-sophisticated approaches to the cachexia-anorexia syndrome. Participants at the National Cancer Institute Workshop concluded that we do not need to wait for further clarification of the pathophysiology of the cachexia-anorexia syndrome before launching a coordinated series of clinical studies. The design and conduct of these studies will be e n h a n c e d if investigators can agree u p o n a taxonomy codifying the various aspects of the cachexia-anorexia syndrome. Adoption of a standard battery of assessment techniques should also be considered. Protocols should not only consider biologic issues but must also encompass considerations of the
Vol. I0 No. 2 February 1995
Cachexia-Anorexia-Asthenia
153
1 BURDEN OF Determine health status using health status indicators
Fig. 1. The McMaster Loop.
2 ETIOLOGY OR CAUSATION Identify and assess possible c a u s e s o f b u r d e n o f illness
6 MONITORING & REASSESSMENT Ongoing monitoring using m a r k e r s s e l e c t e d to i n d i c a t e success and reassessment of m a g n i t u d e o f b u r d e n o f illness
3 COMMUNITY EFFECTIVENESS /,-~sess b e n e f i t / h a r m r a t i o o f potentially feasible interventions and estimate r e d u c t i o n o f b u r d e n o f illness i f
SYNTHESIS & DIFLEMENTATION Integration of feasibility, I m p a c t a n d e f f i c i e n c y to m a k e recom mendations
EFFICIENCY Determine rclationshi p b e t w e e n costs a n d effects of options within and across programs
impact of interventions on health-care costs, b o t h to society and the family, and assessments of the effects of therapy on patient/family quality of life. Following presentations on the pathophysiology, assessment, and c u r r e n t clinical managem e n t of cachexia-anorexia, the participants discussed a series of strategies that, with support, could be successfully introduced without delay. T h e workshop r e c o m m e n d a t i o n s are listed below.
General Recommendations A s t h e n i a - C a c h e x i a - A norexia in Cancer Patients
1. The c a c h e x i a - a n o r e x i a - a s t h e n i a synd r o m e should be assigned a high priority for research support as it (a) devastates family relations and makes the patient d e p e n d e n t u p o n family and health-care institutions; (b) results in a r e q u i r e m e n t for expensive medical care; and (c) is a promising target for intervention which can reduce patient-family suffering and the associated high costs of care during the last days of life. 2. Cancer control represents a series of
preventive strategies. In keeping with this concept, research interventions should be available to patients early in the trajectory of the cachexia-anorexia-asthenia cascade. For this to occur, (a) cancer centers should recognize that anticancer therapy goes beyond destructive therapeutic modalities and encompasses approaches aimed at altering t u m o r biology and associated symptoms, and (b) cancer centers should create a milieu wherein studies on symptom control can flourish. 3. Family studies d e m o n s t r a t e that the c a c h e x i a - a n o r e x i a - a s t h e n i a complex ranks at the top of physical causes of suffering and contributes to psychosocial distress. T h e priorities of patients and families should be reflected in cancer research studies. 4. C o n s o n a n t with this observation, cancer research o u t c o m e measures should emphasize (a) i m p r o v e m e n t in function a n d (b) satisfaction with therapy. 5. While laboratory scientists are making progress in elucidating the pathophysiology of the cachexia-anorexia-asthenia complex, their studies are not sufficiently linked in a c o n t i n u u m with clinical research. Conversely, clinical research leads, such as the effect of progestational agents on the cachexia-ano-
154
MacDonald et al.
rexia-asthenia complex, have not been sufficiently applied to laboratory models. Priority should be assigned to studies bridging the two research reahns. 6. Expertise relevant to the cachexia-anorexia complex is f o u n d in disciplines as yet not involved in cancer research. Proposals that recruit this expertise in coordinated studies should be encouraged. 7. The mechanisms of the cachexia-anorexia-asthenia complex may vary from tumor to tumor. For example, muscle weakness and fatigue are c o m m o n in advanced breast cancer patients, but weight loss is relatively uncommon. Efforts should be made to enroll patients, from specific disease categories.
Specific Recommendations Taxonomy The descriptive terminology and staging of the cachexia-anorexia-asthenia complex are not sufficiently defined. The formation of working groups to develop a taxonomy that can be subsequently used in research studies represents an early priority for action. Assessment
The NCI-CCS should support a workshop to establish a standard assessment panel for studies on the cachexia-anorexia-asthenia complex. Colleagues to be invited who are usually not involved in cancer research include • Neurologists knowledgeable in muscle studies • Geriau'icians, physiotherapists, and occupational therapists knowledgeable in function assessment • Nutritional experts knowledgeable in the analysis of body composition and nutrients • Health-care economists • Family/patient representatives Categories for assessment may include • Changes in patient function (psychosocial and physical) • Cost-benefit studies • Changes in body composition • Measurement of select metabolic abnormalities • Measurement of associated neurologic abnormalities
Vol. 10 No. 2 February 1995
• Measurement of associated immunologic abnormalities While the suffering dimension of the cachexiaanorexia-asthenia complex is well established, the economic costs are less clear. The NCICCS should encourage baseline studies on associated health-care costs. Therapy The impact of progestational agents on the cachexia-anorexia-asthenia complex may be an observation of seminal importance. As good animal models of tumor cachexia exist, studies of the effects of progestational agents and related anabolic agents in these models should be encouraged. Clinical studies involving the following pharmacologic strategies should be encouraged: 1. Progestational agents (P.A.)--stress outcomes on patient function and family life 2. Anabolic steroids--comparison with progestational agents 3. Dietary interventions involving omega-3 fatty acids ( m e n h a d e n oil) and branchedchain amino acids 4. Combination approaches P.A. plus cannabinoids P.A. plus dietary supplements P.A. plus prokinetic agents P.A. plus central nervous system (CNS) stimulants (for example, methylphenidate in asthenic patients) Sufficient information is already available from research on the cachexia-anorexia-asthenia complex to be applied in our clinics. A working group should be commissioned to bring forward clinical guidelines for the current assessment and m a n a g e m e n t of patients in cancer centers and the community.
FoUow-Up An audit of the disposition of researchstrategy proposals should be carried out: Process: • Generation of research proposals • Response of CCS-NCI and other agencies to these proposals • Monitoring of Canadian studies and grants panel responses
Vol. 10 No. 2 February 1995
Cachexia-Anorexia-Asthenia
Outcome: • Publication of statements from granting a g e n c i e s l e n d i n g e n c o u r a g e m e n t to res e a r c h e r s to d e v e l o p m u h i d i s c i p l i n a r y coordinated proposals • Publication of health professional guidelines • Review o f l i t e r a t u r e c i t a t i o n • Review o f s u b s e q u e n t p r a c t i c e c h a n g e
Ref~e$ 1. Bruera E, Fainsinger RL. Clinical management of cachexia and anorexia. In: Doyle D, Hanks GWC, MacDonald N, eds. Oxford textbook of palliative medicine, vol 4. London: Oxford University Press, 1993;330-337. 2. Warren RS. The immediate causes of death in cancer. A m J Med Sci 1932;184:610. 3. Anonymous. It has been said, collected by Harold FM. Perspect Biol Med 1992;35:594. 4. Dewys WD, Begg N, Lavin PT, et al. Clinical studies on prognostic effect of weight loss prior to chemotherapy in cancer patients. Am J Med 1980;69:491497. 5. Moldawer LL, Georgieff M, Lundholm tL Interlenkin-1, tumor necrosis factor-alpha (cachectin)
155
and the pathogenesis of cancer cachexia. Clin Physiol 1987;7:263-274. 6. Bendtzen IC Interleukin-1, interleukin-6 and tumor necrosis factor in infection, inflammation and immunity. Immunol Lett 1988;19:183-192. 7. Evans RD, Argiles JM, Williamson DH. Metabolic effects of tumor necrosis factor-co (cachectin) and interleukin-1. Clin Sci 1989;77:357-364. 8. Langstein HN, Fraker DL, Norton JA. Reversal of cancer cachexia by antibodies to interferon-gamma but not cachectin/tumor necrosis factor. Surg Forum 1989;15:408-410. 9. Beck SA, Mulligan HD, Tisdale MJ. Lipolytic factors associated with murine and human cancer cachexia. J Natl Cancer Inst 1990;82:1922-1926. 10. Alexander RH, Norton JA. Pathophysiology of cancer cachexia. In: Doyle D, Hans G, MacDonald N, eds. Oxford textbook of palliative medicine, vol 4. London: Oxford University Press, 1993;316-329. 11. Bruera E, MacDonald RN. Nutrition in cancer patients.J Pain Symptom Manage 1988;3:133-138. 12. Bruera E, Roca E, Cedaro L, et al. Action of oral methyprednisolone in terminal cancer patients: a prospective, randomized double-blind study. Cancer Treat Rep 1985;69:751-754. 13. Bennett K, Tugwell P, Sackett D, Haynes B. Relative risks, benefits, and costs of intervention. In: Warren KS, Adel AAF, Mahmoud A, eds. Tropical and geographical med, 2nd ed. New York: McGraw Hill, 1990:205-228.
Journal of Pain and Symptom Management 151
Cachexia-Anorexia-Asthenia Neil M a c D o n a l d , MD, H. R i c h a r d A l e x a n d e r , MD, a n d E d u a r d o Bruera, MD Centerfor Bioethics (N.M.), Clinical Research Institute of Montreal, Montreal, Quebec; and Edmonton General Hospital (E.B), Edmonton, Alberta, Canada; and Surgery Branch (H.R.A.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland
Abstract The National Cancer Institute (Canada) sponsored a workshop on symptom control in Banff Alberta, in October 1993. This article reports on the workshop recommendations for research on one symptom complex, the cachexia-anorexia-asthenia syndrome. In addition to encouraging stud), generation, the recommendations provide a baseline for assessing the scope and strength of future Canadian research initiatives on cachexia-anorexia-asthenia. J Pain Symptom Manage 1995;10:151-155.
Key Words Cachexia, anorexia, research workshop
Introduction Weight loss, asthenia, and anorexia, often associated with chronic nausea, are a m o n g the most c o m m o n symptom problems afflicting patients with advanced cancer, l Earlier, prec h e m o t h e r a p y studies suggest that weight loss and associated metabolic abnormalities may account for 25% of cancer deaths9 As patients with cachexia-anorexia are often weak and unable to care for themselves, family resources are severely taxed, and patients often require institutional care for p r o l o n g e d periods prior to death. T h e term " c a c h e x i a - a n o r e x i a s y n d r o m e " is used somewhat loosely, as the defining qualities of the syndrome and the c o n s e q u e n t tests that m o n i t o r progress or regression remain imprecise. T h e r e is a Chinese proverb that states " T h e beginning of wisdom is to call things by
Address reprint requests to: Neil MacDonald, MD, Center for Bioethics, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, H2Q 1R7 Canada. Acceptedfcrr publication:June 20, 1994. © U.S. Cancer Pain Relief Committee, 1995 Published by Elsevier, NewYork, NewYork
their right names. '''4 A m o d e r n coiner of aphorisms, Sir Peter Medawar has said, " N o new truth will declare itself f r o m inside a h e a p of facts. '':~ At present, a " h e a p of facts" g a r n e r e d by research workers working in disparate areas is available to the clinical investigator c o n c e r n e d with cancer cachexia. T h e web c o n n e c t i n g these observations in a c o h e r e n t mosaic, however, remains to be fully woven. Some salient features stand out, however, including 1. T h e cachexia-anorexia complex has a variable incidence d e p e n d i n g on the type of primary tumor. 4 It is relatively u n c o m m o n in patients with one f o r m of a d e n o c a r c i n o m a , breast cancer, while it is very c o m m o n in certain o t h e r forms of a d e n o c a r c i n o m a such as lung cancer and pancreatic cancer. Wasting is not c o m m o n l y observed in the hematologic malignancies although myelodysplastic syndromes are often associated with e x t r e m e wasting. 2. Studies c o m p a r i n g the biology of those tumors that show a propensity to develop c a c h e x i a - a n o r e x i a with those that do not, remain to be carried out. T h e syndrome is 0885-3924/95/$9.50 SSDI 0885-3924(94)00077-X
152
MacDonald et al.
probably caused by chemical factors produced as a result of a host response or directly by the tumor. A n u m b e r of cytokines that can produce symptoms mimicking the cachexia-anorexia syndrome have been identified. The list includes t u m o r necrosis factor, interleukins 1 and 6, and interferon 7. However, specific cytokine abnormalities 5-8 have not been linked to cancer cachexia-anorexia in humans, and noncytokine chemical factors have also been implicated. 'j We presume that an interactive cascade involving multiple chemical factors is responsible. 3. Metabolic abnormalities may precede weight loss in animal cachexia-anorexia tumor models, I° and it is presumed that the same p h e n o m e n a occur in humans. While subsequent decrease in nutrient intake will compound the problem, loss of appetite appears to be related to the onset of these metabolic abnormalities, rather than acting as a primary cause of the cachexia-anorexia syndrome. 4. Clinicians must be careful to diagnose those situations where cancer patients lose weight because of simple starvation, potentially corrected with parenteral or enteral nutrition, rather that assigning all changes in weight to the cachexia-anorexia syndrome. Correctable examples include some patients with head and neck cancer with obstruction of the upper digestive tract, and some patients with ovarian carcinoma with intermittent small-bowel obstruction. Notwithstanding the occasional patient who is truly starving, the vast majority of cancer patients who lose weight suffer from a complex metabolic aberration that does not respond to simple replacement of nutrients. A n u m b e r of studies have demonstrated that replacement of calories using standard enteral or parenteral diets does not result in meaningful weight gain or improvement in quality of life or tumor response. II It remains to be d e t e r m i n e d whether the use of special dietary supplements directed at correction of specific metabolic abnormalities will change the current wisdom that dietary supplementation does not help patients with the cachexia-anorexia syndrome. 5. Similar to the observations made with diet, drug trials attempting to increase appetite and weight generally have not been successful. Corticosteroids certainly produce an immediate improvement in appetite and occasionally
Vol. 10 No. 2 February 1995
in weight, but the effect is usually short-lived. 12 However, the observation that progestational agents can improve appetite and reverse weight loss is possibly of major importance. It remains to be clearly d e t e r m i n e d whether the immediate improvement in patient well-being produced by progestational agents translates into longer-term improvements in patient energy, mobility, and independence. However, for the first time pharmacologic therapy has significantly impacted upon the cachexia-anorexia syndrome, thus creating the impetus to "work back" from the clinical observation to the laboratory to determine how these agents work. Consequent understanding of an exploitable lead may result in development of more specific agents. The use of progestational agents in combination with other drugs that are relatively ineffective when used alone or with special diets may offer a promising area for future study. The McMaster Loop 1`~ (Figure 1) provides a useful framework for assessing the importance and feasibility of a research initiative. The cachexia-anorexia complex certainly presents an extraordinary b u r d e n for involved patients, families, and society. While its pathophysiology remains to be fully elucidated, sufficient information is available to frame studies linking the laboratory and the bedside. Successful pharmacologic intervention with progestational agents provides a base for immediate projection of further clinical interventions, which could be carried out at reasonable cost and with reasonable anticipation of success. This success could be measured both in terms of alleviating suffering and reducing health-care costs. The lessons learned from these studies, in turn, will lead to more-sophisticated approaches to the cachexia-anorexia syndrome. Participants at the National Cancer Institute Workshop concluded that we do not need to wait for further clarification of the pathophysiology of the cachexia-anorexia syndrome before launching a coordinated series of clinical studies. The design and conduct of these studies will be e n h a n c e d if investigators can agree u p o n a taxonomy codifying the various aspects of the cachexia-anorexia syndrome. Adoption of a standard battery of assessment techniques should also be considered. Protocols should not only consider biologic issues but must also encompass considerations of the
Vol. I0 No. 2 February 1995
Cachexia-Anorexia-Asthenia
153
1 BURDEN OF Determine health status using health status indicators
Fig. 1. The McMaster Loop.
2 ETIOLOGY OR CAUSATION Identify and assess possible c a u s e s o f b u r d e n o f illness
6 MONITORING & REASSESSMENT Ongoing monitoring using m a r k e r s s e l e c t e d to i n d i c a t e success and reassessment of m a g n i t u d e o f b u r d e n o f illness
3 COMMUNITY EFFECTIVENESS /,-~sess b e n e f i t / h a r m r a t i o o f potentially feasible interventions and estimate r e d u c t i o n o f b u r d e n o f illness i f
SYNTHESIS & DIFLEMENTATION Integration of feasibility, I m p a c t a n d e f f i c i e n c y to m a k e recom mendations
EFFICIENCY Determine rclationshi p b e t w e e n costs a n d effects of options within and across programs
impact of interventions on health-care costs, b o t h to society and the family, and assessments of the effects of therapy on patient/family quality of life. Following presentations on the pathophysiology, assessment, and c u r r e n t clinical managem e n t of cachexia-anorexia, the participants discussed a series of strategies that, with support, could be successfully introduced without delay. T h e workshop r e c o m m e n d a t i o n s are listed below.
General Recommendations A s t h e n i a - C a c h e x i a - A norexia in Cancer Patients
1. The c a c h e x i a - a n o r e x i a - a s t h e n i a synd r o m e should be assigned a high priority for research support as it (a) devastates family relations and makes the patient d e p e n d e n t u p o n family and health-care institutions; (b) results in a r e q u i r e m e n t for expensive medical care; and (c) is a promising target for intervention which can reduce patient-family suffering and the associated high costs of care during the last days of life. 2. Cancer control represents a series of
preventive strategies. In keeping with this concept, research interventions should be available to patients early in the trajectory of the cachexia-anorexia-asthenia cascade. For this to occur, (a) cancer centers should recognize that anticancer therapy goes beyond destructive therapeutic modalities and encompasses approaches aimed at altering t u m o r biology and associated symptoms, and (b) cancer centers should create a milieu wherein studies on symptom control can flourish. 3. Family studies d e m o n s t r a t e that the c a c h e x i a - a n o r e x i a - a s t h e n i a complex ranks at the top of physical causes of suffering and contributes to psychosocial distress. T h e priorities of patients and families should be reflected in cancer research studies. 4. C o n s o n a n t with this observation, cancer research o u t c o m e measures should emphasize (a) i m p r o v e m e n t in function a n d (b) satisfaction with therapy. 5. While laboratory scientists are making progress in elucidating the pathophysiology of the cachexia-anorexia-asthenia complex, their studies are not sufficiently linked in a c o n t i n u u m with clinical research. Conversely, clinical research leads, such as the effect of progestational agents on the cachexia-ano-
154
MacDonald et al.
rexia-asthenia complex, have not been sufficiently applied to laboratory models. Priority should be assigned to studies bridging the two research reahns. 6. Expertise relevant to the cachexia-anorexia complex is f o u n d in disciplines as yet not involved in cancer research. Proposals that recruit this expertise in coordinated studies should be encouraged. 7. The mechanisms of the cachexia-anorexia-asthenia complex may vary from tumor to tumor. For example, muscle weakness and fatigue are c o m m o n in advanced breast cancer patients, but weight loss is relatively uncommon. Efforts should be made to enroll patients, from specific disease categories.
Specific Recommendations Taxonomy The descriptive terminology and staging of the cachexia-anorexia-asthenia complex are not sufficiently defined. The formation of working groups to develop a taxonomy that can be subsequently used in research studies represents an early priority for action. Assessment
The NCI-CCS should support a workshop to establish a standard assessment panel for studies on the cachexia-anorexia-asthenia complex. Colleagues to be invited who are usually not involved in cancer research include • Neurologists knowledgeable in muscle studies • Geriau'icians, physiotherapists, and occupational therapists knowledgeable in function assessment • Nutritional experts knowledgeable in the analysis of body composition and nutrients • Health-care economists • Family/patient representatives Categories for assessment may include • Changes in patient function (psychosocial and physical) • Cost-benefit studies • Changes in body composition • Measurement of select metabolic abnormalities • Measurement of associated neurologic abnormalities
Vol. 10 No. 2 February 1995
• Measurement of associated immunologic abnormalities While the suffering dimension of the cachexiaanorexia-asthenia complex is well established, the economic costs are less clear. The NCICCS should encourage baseline studies on associated health-care costs. Therapy The impact of progestational agents on the cachexia-anorexia-asthenia complex may be an observation of seminal importance. As good animal models of tumor cachexia exist, studies of the effects of progestational agents and related anabolic agents in these models should be encouraged. Clinical studies involving the following pharmacologic strategies should be encouraged: 1. Progestational agents (P.A.)--stress outcomes on patient function and family life 2. Anabolic steroids--comparison with progestational agents 3. Dietary interventions involving omega-3 fatty acids ( m e n h a d e n oil) and branchedchain amino acids 4. Combination approaches P.A. plus cannabinoids P.A. plus dietary supplements P.A. plus prokinetic agents P.A. plus central nervous system (CNS) stimulants (for example, methylphenidate in asthenic patients) Sufficient information is already available from research on the cachexia-anorexia-asthenia complex to be applied in our clinics. A working group should be commissioned to bring forward clinical guidelines for the current assessment and m a n a g e m e n t of patients in cancer centers and the community.
FoUow-Up An audit of the disposition of researchstrategy proposals should be carried out: Process: • Generation of research proposals • Response of CCS-NCI and other agencies to these proposals • Monitoring of Canadian studies and grants panel responses
Vol. 10 No. 2 February 1995
Cachexia-Anorexia-Asthenia
Outcome: • Publication of statements from granting a g e n c i e s l e n d i n g e n c o u r a g e m e n t to res e a r c h e r s to d e v e l o p m u h i d i s c i p l i n a r y coordinated proposals • Publication of health professional guidelines • Review o f l i t e r a t u r e c i t a t i o n • Review o f s u b s e q u e n t p r a c t i c e c h a n g e
Ref~e$ 1. Bruera E, Fainsinger RL. Clinical management of cachexia and anorexia. In: Doyle D, Hanks GWC, MacDonald N, eds. Oxford textbook of palliative medicine, vol 4. London: Oxford University Press, 1993;330-337. 2. Warren RS. The immediate causes of death in cancer. A m J Med Sci 1932;184:610. 3. Anonymous. It has been said, collected by Harold FM. Perspect Biol Med 1992;35:594. 4. Dewys WD, Begg N, Lavin PT, et al. Clinical studies on prognostic effect of weight loss prior to chemotherapy in cancer patients. Am J Med 1980;69:491497. 5. Moldawer LL, Georgieff M, Lundholm tL Interlenkin-1, tumor necrosis factor-alpha (cachectin)
155
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