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Current and Future Care of Patients with the Cancer Anorexia-Cachexia Syndrome

Multimodality therapy of Cancer cachexia

Since muscle wasting and poor caloric intake are multifactorial in nature, a comprehensive multidimensional approach of pharmacologic and non-pharmacologic interventions should be used for cancer cachexia. Ideally, treatment should be individualized, taking into account the patient's overall condition, the principal mechanisms of their weight loss, and their goals of care. In future, patients with a genetic predisposition to developing cachexia may be targeted earlier, when they are still in the ‘pre-cachexia ‘stage. Unfortunately our current options are more limited for the screening and management of patients that develop this devastating condition.

Systematic reviews suggest current pharmacological options such as progestational agents1, fish oil2, Non-Steroidal Anti-inflammatories3 or thalidomide4 are restricted by side-effects and limited efficacy. However, some of these medications in combination with supportive care and nutritional counseling have been incorporated into multimodal clinical trials, showing improved clinical outcomes. A multi-arm randomized controlled trial showed a progestin in combination with fish oil, L-carnitine, and thalidomide significantly increased appetite, LBM (p = 0.007), and spontaneous physical activity5. All patients were provided with dietary counseling and nutritional supplements. Similarly, another group has adopted an approach of combining medications with enteral and parenteral nutrition. Beta blockers and insulin in combination with nonsteroidal anti-inflammatories (NSAIDs), reduced resting energy expenditure, attenuated weight loss and improved in survival (p = 0.03) in patients with cancer cachexia6.

Despite these encouraging studies there is still an unmet need for an effective single pharmacologic agent, and although we now have promising candidates7, any specific anti-cachexia intervention would still need to be incorporated into a multimodality approach.

Multimodal therapy includes interdisciplinary care

Multimodal therapy should not be confined only to pharmacological agents; therapy must be extended to include the expertise of other disciplines such as dietitians, physical and occupational therapists, psychologists, social workers and nurses. A nutritional assessment measure such as the Patient-Generated Subjective Global Assessment (PG-SGA), a validated tool endorsed by the American Dietetic Society is useful to identify reversible factors contributing to poor oral intake. A brief version, the abridged PGSGA8 can be administered by professionals other than dietitians and correlates with cancer cachexia features such as increased inflammation, decreased muscle strength, loss of fat mass, increased hospitalization, decreased chemotherapy tolerance and shorter life expectancy. Individualized nutritional counseling and education by dietitians have also shown improved clinical outcomes in trials. Weight and survival improved in patients receiving radiotherapy for colorectal cancer9, while a systematic review also found improvements in quality of life and nutritional status in head and neck cancer10. More recently a pilot trial of intensive individualized nutritional therapy in cachectic patients maintained body weight, decreased hospitalizations and improved survival11.

In smaller academic centers and in community practices where resources and support staff may be limited, physicians and nurses may be the sole providers responsible for the assessment and management of both cancer and cachexia. Identifying weight loss of >5% (the core criterion for cancer cachexia) along with modifiable symptoms that contribute to poor caloric intake can be implemented in daily clinical practice. In North America the Edmonton symptom assessment scale (ESAS) is commonly used to identify symptoms in patients with cancer, including poor appetite, pain, nausea, and depression that have an impact on nutritional intake. Treating these symptoms with relatively inexpensive medications can improve appetite and body weight even in patients with advanced cancer. The ESAS can be done in less than 5 minutes and has been incorporated into a standardized assessment for a large population of oncology outpatients12. By incorporating brief screening tools, nurses can provide basic nutritional advice, assess symptoms that may be contributing to poor caloric intake, and provide psychological support13.

Although a systematic review found insufficient evidence for the efficacy of exercise in cancer cachexia14 pre-clinical studies have shown promising results, indicating exercise may be an important future component of multimodal therapy. Exercise improves mitochondrial dysfunction in animal models of cachexia15, decreases oxidative stress16 and modulates pro-inflammatory cytokines17. Resistance training also increases the lean body mass of patients receiving chemotherapy, and improves chemotherapy completion rate18, suggesting trials in cachectic patients are long overdue.

Conclusion

While we eagerly await the development of promising new therapies targeting muscle19 and proinflammatory cytokines20, and the favorable results of phase III studies21 suggest our patients may soon benefit from an effective pharmacological agent, we must consider all the other vital facets of multimodal therapy. Figure 1 illustrates potential combination therapies that could provide simultaneous, multifaceted therapy targeting the different mechanisms contributing to CAC22S introduced against a background of “best supportive care” that includes optimal symptom management and physician–patient communication.

Egidio Del Fabbro, MD
Director Palliative Care Program, Virginia Commonwealth University

References

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