The Cancer Anorexia–Cachexia Syndrome

Nelson, Kristine A.; Walsh, Declan

doi:10.1016/s0885-3924(02)00508-0

Cited by 54 publications

(40 citation statements)

References 22 publications

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“…This syndrome compromises quality of life and contributes to mortality. 10,11 Cancerassociated weight loss reflects activation of host catabolism with loss of muscle protein mass and body fat. As with other aspects of human cancer, this has been difficult to reproduce in animal models.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14][15][16] Tumor cell-and host-produced cytokines such as IL-6, TNF-␣ and IFN-␥ are thought to play an important role in the catabolism and weight loss associated with several malignant and nonmalignant conditions. 10,11,[17][18][19] However, the specific contribution of human tumor cell-secreted IL-6 to body weight loss has not been described. We hypothesized that neutralization of tumor cell-secreted IL-6 could inhibit body weight loss.…”

Section: Discussionmentioning

confidence: 99%

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CNTO 328, a monoclonal antibody to IL‐6, inhibits human tumor‐induced cachexia in nude mice

Zaki¹,

Nemeth²,

Trikha³

2004

Intl Journal of Cancer

104

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IL-6 is a multifunctional cytokine implicated in several cancers. IL-6 is a growth factor for certain tumors and contributes to drug resistance, cachexia and bone resorption. Cachexia is characterized by progressive weight loss and depletion of host reserves of adipose tissue and skeletal muscle. We have developed CNTO 328 (cCLB8), a humanmouse chimeric MAb to IL-6 (K d approx. 10 ؊12 M) that inhibits IL-6 function. A phase I study with CNTO 328 in multiple myeloma patients demonstrated that the antibody was safe and had a circulating half-life of approximately 17 days. Since IL-6 is implicated in cachexia, we hypothesized that CNTO 328 could inhibit tumor-induced cachexia. We used 2 human tumor-induced cachexia models in nude mice. In the first model, human melanoma cells were inoculated in female nude mice. Control treated animals lost 19% (؎7.7%) body weight from day 0 to day 31, whereas CNTO 328 (10 mg/kg)-treated animals lost only 1.5% (؎1.3%) body weight from day 0 to day 31 (p ‫؍‬ 0.023). Cachexia (wasting syndrome) is a debilitating state of involuntary weight loss that is characterized by hypercatabolism of the body's carbon sources, proteins and lipids, for conversion into energy. 1 Cachexia is induced by a variety of pathologic conditions, including cancer, where an estimated 30% of cancer deaths are attributed to cachexia. Tumor necrosis factor (TNF)-␣, IL-1, IFN-␥ and IL-6 contribute to many of the host changes seen in cancer cachexia, including loss of appetite, loss of body weight and induction of acute-phase proteins. 2 These cytokines induce cachexia by altering the metabolism of lipids and proteins. IL-6 is a 26 kDa protein with a broad range of activities, involving not only immunomodulation but also hemostatic, neuroendocrine and cancer-associated disorders. 3 IL-6 is an acute phase-inducing cytokine that is secreted to a large extent by human adipose tissue under noninflammatory conditions. 4 It also influences atrophy and increases catabolism of muscle protein. IL-6 is expressed together with its receptor in neurons of hypothalamic nuclei that regulate body composition. IL-6 levels in serum correlate with body mass index (BMI), and IL-6-deficient mice developed mature-onset obesity. 4 Although several studies have suggested that host-derived IL-6 contributes to cachexia, the role for tumor cell-secreted IL-6 in cachexia is less clear.IL-6 is also implicated in regulating the growth and differentiation of several malignant diseases. The ability of IL-6 to mediate tumor cell survival and disease progression has been demonstrated by the inhibitory effects of an anti-IL-6 MAb on tumor growth both in vitro and in vivo. Blockade of IL-6 can inhibit growth of human glioblastoma cells in vitro. 5 Using the same approach, it was shown that injection of an antihuman IL-6 MAb prolonged the survival of human lymphoma-bearing mice. 6 Several clinical trials using monoclonal antibodies (MAbs) against IL-6 have been conducted on various diseases, including plasma cell leukemia, multiple myeloma, B-lymphop...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CNTO 328, a monoclonal antibody to IL‐6, inhibits human tumor‐induced cachexia in nude mice

Zaki¹,

Nemeth²,

Trikha³

2004

Intl Journal of Cancer

104

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“…The development of cachexia is common in people with solid tumours such as pancreatic, lung, gastric and colorectal cancer. Cancer cachexia is associated with metabolic alterations that are likely to affect energy expenditure [7,8,9]. Patients with cancer cachexia are often malnourished; therefore, the provision of adequate nutrition support is essential for maintaining or improving nutritional status.…”

Section: Introductionmentioning

confidence: 99%

The agreement between measured and predicted resting energy expenditure in patients with pancreatic cancer — A pilot study

Bauer

Reeves²,

Capra³

2003

Clinical Nutrition

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Objective To compare measured resting energy expenditure to resting energy expenditure predicted from eight published prediction equations in a sample of patients with pancreatic cancer.Design Cross-sectional study.Setting Ambulatory patients of a tertiary private hospital.Participants Eight patients with pancreatic cancer (5 males, 3 females; age: 62.0±5.2 years; BMI: 24.4±3.2 kg/m 2 ; weight loss: 12.1±6.0%; mean±SD). MethodsResting energy expenditure was measured using indirect calorimetry and predicted from eight published prediction methods (Harris-Benedict with no injury factor, Harris-Benedict with 1.3 injury factor, Schofield, Owen, Mifflin, Cunningham, and Wang equations and the 20 kcal/kg ratio). Body composition was assessed by deuterium oxide dilution technique. Statistical analysis was performed by using the method of Bland and Altman, and the Student's t-test. ResultsThe Harris-Benedict equations with an injury factor of 1.3 resulted in a significantly higher mean predicted resting energy expenditure compared to measured resting energy expenditure, while there was no significant difference between mean measured and predicted resting energy expenditure and the other 7 methods. At an individual level, the limits of agreement are wide for all equations. The best combination of low bias and narrowest limits of agreement was observed in the prediction of resting energy expenditure from the Wang equation (based on fat free mass) and the HarrisBenedict equation (based on weight and height). ConclusionAt a group level, there is agreement between mean measured and predicted resting energy expenditure with the exception of the Harris-Benedict equation with an injury factor of 1.3. The results of this pilot study suggest that, for an individual, the limits of agreement are wide, and clinically important differences in resting energy expenditure would be obtained. Clinicians need to be aware of the limitations of the use of resting energy expenditure prediction equations for individuals.

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“…It has been suggested that the loss of adipose tissue accounts for the majority of the weight loss, but the loss of muscle accounts for most of the morbidity and mortality (13,14) . However, the extent of weight loss that is prognostic is not well defined (15,16) and performance status is recognised to be subjective (17) and therefore their reliability has been questioned.…”

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confidence: 99%

An inflammation-based prognostic score and its role in the nutrition-based management of patients with cancer

2008

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Progressive involuntary weight loss, in particular the loss of lean tissue, is common in patients with advanced cancer and has long been recognised to result in a deterioration in performance status and quality of life, increased morbidity and mortality. The aetiology of such weight loss or cachexia is complex and involves both tumour and host responses. Thus, identification of patients who are or are likely to become cachectic has been problematic. In addition to a reduction in appetite and increased satiety leading to poor dietary intake, there is now increasing clinical evidence that the activation of a chronic ongoing systemic inflammatory response is one of the earliest and most important contributory factors to cachexia. Such findings help to explain the failure of simple nutritional programmes to reverse weight loss adequately in patients with cancer. In the present paper the development of an inflammationbased score is described, which is derived from the acute-phase proteins C-reactive protein and albumin and is termed the Glasgow prognostic score (GPS). Its value as a predictor of survival, independent of tumour stage, performance status and treatment (active or palliative), has been shown in a variety of advanced common solid tumours. The nature of the relationship between the GPS, appetite, body composition, performance status and quality of life of the patient with advanced cancer will be described. Recently, it has become evident that the systemic inflammatory response is also present in a smaller proportion of patients with primary operable cancer and is also predictive of disease progression and poor survival. The role of GPS in clinical decision making will be discussed.

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The Cancer Anorexia–Cachexia Syndrome

Cited by 54 publications

References 22 publications

CNTO 328, a monoclonal antibody to IL‐6, inhibits human tumor‐induced cachexia in nude mice

CNTO 328, a monoclonal antibody to IL‐6, inhibits human tumor‐induced cachexia in nude mice

The agreement between measured and predicted resting energy expenditure in patients with pancreatic cancer — A pilot study

An inflammation-based prognostic score and its role in the nutrition-based management of patients with cancer

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