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Clinical practice guidelines on Cancer Cachexia in advanced cancer patients

Radbruch L, Elsner F, Trottenberg P, Strasser F, Fearon K. Aachen, Department of Palliative Medicinen/ European Palliative Care Research Collaborative;2010. Available at: http://www.epcrc.org

This publication represents a consensus- and evidence-based clinical practice guideline for the management of Cachexia in advanced cancer patients, with a focus on refractory cachexia, on behalf of the European Palliative Care Research Collaborative (EPCRC http://www.epcrc.org). The patient group covered patients with advanced cancer, and the target audience was intended as all health professionals involved in the provision of palliative care and in the care of patients with advanced cancer.

Key points of the EPCRC 2010 guidelines are summarized hereafter.

Definition

Cancer cachexia is a multi-factorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. The pathophysiology is characterized by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism.


Stages

Cancer cachexia represents a continuum with three stages of clinical relevance: pre-cachexia, cachexia and refractory cachexia. Not all patients traverse the entire spectrum. At present there are no robust biomarkers to identify those pre-cachectic patients who are likely to progress further down the trajectory or the rate at which they will do so. The cachexia stages are defined essentially on the basis of the patient’s clinical characteristics and circumstances (see also Fearon et al. Lancet Oncol. 2011;12(5):489-95).


Signs & symptoms

Assessment of signs and symptoms has to cover different dimensions of cachexia. A model with 4 dimensions has been proposed, including Storage, Intake, Potential and Perfomance (SIPP).


Storage Assess gap of usual to current weight, speed of weight loss, weight loss corrected for fluid retention or obesity, deficits for specific nutrients
Intake Assess anorexia, early satiety, nausea, vomiting, disturbances of taste or smelling, other gastrointestinal symptoms, percentage of normal intake, dietary diary for 1-2 days
Potential Assess tumor [catabolic] activity, C-reactive protein
Performance Assess performance status, cachexia-related suffering, prognosis

Assessment

Assessment of cachexia and anorexia should cover the signs and symptoms in the dimensions described above. Parameters that should be considered for assessment are listed below. Screening should include at least appetite and gastrointestinal symptoms, history of weight change and BMI, CRP and performance status.


Subjective symptoms Appetite, early satiety, nausea, vomiting, disturbances of taste or smelling, other gastrointestinal symptoms, weakness, disease-related burden, well-being
History Weight change, speed of weight loss, percentage of normal intake
Clinical examination Inspection of mouth, abdomen, hydration status, oedema, body weight, perceived physical strength
Laboratory examination CRP, blood sugar profile, testosterone
Activity monitoring Performance status (ECOG or Karnofsky), upper limb hand-grip dynamometry, body-worn activity meters
Body composition Cross-sectional imaging (CT or MRI), dual energy x-ray imaging (DEXA), anthropometry (mid-arm muscle area), bioelectrical impedance analysis (BIA)

Patient management

Management of cachexia must take into account the patient’s prognosis.
Health professionals should discuss all treatment options with the patient and ensure that they are well informed. Patients should have equal access to appropriate assessment and management of cachexia whether they are homecare, day care or inpatients.


The treatment goal for cachexia should be the reversal of the loss of body weight and muscle mass. As a minimal goal body weight should be maintained and further loss prevented.

The treatment approach should be multimodal and similar to pre-cachexia. This includes detailed assessment and repeated monitoring, vigorous nutritional support, anti-inflammatory treatment, treatment of secondary gastrointestinal symptoms and other causes for decreased oral nutritional intake as well as evaluation of anti-neoplastic options to reduce the catabolic drive of the cancer.

Treatments

The expert group identified key questions on nutritional treatment, non-drug treatment, drug treatment, multi-dimensional therapy and prophylaxis as major domains. Main recommendations on these domains are summarized hereafter.


Nutritional Treatment

  • Enteral nutrition therapy may be partially effective for selected patient groups (level of recommendation: strong positive; mean consensus 7.03 on a scale from 0=completely disagree to 10=completely agree). For refractory cachexia the provision of appetising food and enteral nutritional support in a context that does not add to eating-related distress is recommended.

Non-Drug-Treatment

  • There is evidence that non-drug treatment is effective in the treatment of cancer cachexia (level of recommendation: strong positive; mean consensus 8.17). However, evidence for patients with refractory cachexia is insufficient.
  • There is some evidence that counseling has positive effects on nutritional status and quality of life in cancer patients undergoing anti-neoplastic therapy (level of recommendation: strong positive; mean consensus 9.08). There is no evidence to support or refute the value of counseling in advanced cancer/refractory cachexia.
  • There some evidence that psychotherapeutic interventions (relaxation therapy) have positive effects on quality of life (level of recommendation: strong positive; mean consensus7.14). There is no evidence that psychotherapeutic interventions have an effect on nutritional status. Moreover, for refractory cachexia, reduced performance status and short prognosis may preclude this intervention.
  • In cancer patients, physical training and other physical treatment options are beneficial as a preventive procedure to maintain functional status. The activities and training interventions have to be individualized (overall level of recommendation: strong positive; mean consensus 7.92). However, most research has been done in patients treated with curative intent, and it is not clear to what extent physical training is appropriate in patients with advanced cancer/refractory cachexia.

Drug Treatment

  • Thalidomide and cytokine antagonists: There is not enough evidence on the net benefit of thalidomide or cytokine antagonists (level of recommendation: weak negative; mean consensus 7.57). The use of thalidomide is not recommended in patients with refractory cachexia.
  • Cannabinoids: Cannabinoids may increase appetite in selected patients but overall there is not enough evidence to support their use (level of recommendation: weak negative; mean consensus 7.78). The use of cannabinoids is not recommended in patients with refractory cachexia.
  • Omega-3-fatty acids, including eicosapentaenoic acid (EPA): There is not enough evidence to reach consensus on the net benefit of omega-3-fatty acids in patients with advanced cancer/refractory cachexia ( mean consensus 6.54). Omega-3-fatty acids may be effective in specific patients who achieve effective blood levels. More research is needed to optimize compliance and determine the potential role of omega-3-fatty acids in multimodal regimens.
  • Megestrol and progestins: Megestrol or progestins seem to stimulate appetite and increase body weight, though not muscle mass (level of recommendation: weak positive; mean consensus 7.73). Progestins should be considered for patients with refractory cachexia and with anorexia as a major distressing symptom.
  • Steroids: Steroids may be beneficial in patients with refractory cachexia for stimulation of appetite and improvement in quality of life (level of recommendation: strong positive; mean consensus 8.50). However, the use of steroids is recommended for short (maximal 2 weeks) periods as longer duration of treatment may increase the burden on the patient from side effects and may cause a deterioration in muscle strength.
  • Non-steroidal anti-inflammatory drugs: Non-steroidal anti-inflammatory drugs alone seem to offer little benefit (level of recommendation: weak negative; mean consensus 7.36). NSAIDs may be more effective as part of a multi-modal intervention. The indication is still under discussion for patients with high CRP-blood levels. The use of NSAIDs for treatment of refractory cachexia is not recommended.
  • Prokinetics: Prokinetics are recommended in patients with early satiety, chronic nausea, dyspeptic symptoms and gastroparesis (level of recommendation: weak positive; mean consensus 8.53). There is no evidence that prokinetics will improve the nutritional status of patients with advanced cancer/refractory cachexia.  
  • Anticancer treatment for treating cancer cachexia: The best way to cure cachexia is to cure the cancer. However, for cachectic patients who have progressed through anticancer treatment, the use of further palliative anticancer treatment (where the chance of response is low and where side-effects may lead to further nutritional decline) should be considered very carefully, involving oncological and palliative care expertise (level of recommendation: weak negative; mean consensus 7.97). The use of anticancer treatment for alleviation of refractory cachexia is clearly not recommended.

Multimodal Therapy

  • Multimodal therapy for cancer cachexia should be offered, as a combination of nutrition, medication and non-drug-treatment may be more effective than monotherapy (level of recommendation: weak positive; mean consensus 8.32). However, more research is needed to evaluate the concept also for refractory cachexia.

Prophylaxis

  • Patients at risk of losing weight should be offered prophylactic interventions such as nutritional counseling and physical training, as these interventions are thought to be beneficial in delaying or preventing the development of the anorexia-cachexia syndrome (level of recommendation: weak positive; mean consensus 8.65). Per definition, prophylaxis is not relevant for patients with refractory cachexia.

Conclusions

For patients with refractory cachexia consider the following interventions:


  • That patients with simple starvation/secondary nutrition impact symptoms have been identified. For example, it is important to diagnose constipation, incident pain and other factors that might lead to the false diagnosis of refractory cachexia.
  • Appetising food or ONS within a context that does not exaggerate eating-related distress.
  • Educate patient/family to minimise eating related distress, counsel them about weight loss related distress and end of life issues and appraise rational factors of distress related to eating.
  • Encourage physical activities related to comfort of patients as far as possible, but do not set false goals of muscle mass or strength related to overactivity.
  • Progestational agents for short term use with the major goal of improving the objective symptoms of anorexia.
  • Corticosteroids for very short term use (1-2 weeks) for improvement of appetite, mood, for special life events.

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