What is the appropriate workup and treatment for cachexia?

From the Guidelines

The appropriate workup for cachexia begins with identifying the underlying cause through a comprehensive history, physical examination, and laboratory tests including complete blood count, comprehensive metabolic panel, inflammatory markers, and hormone levels, as recommended by the most recent guidelines 1.

Key Components of Workup and Treatment

• Identifying the underlying cause of cachexia is crucial for effective management.
• Treatment requires a multimodal approach addressing both the underlying condition and the cachexia itself.
• Nutritional support is fundamental, with high-protein, calorie-dense diets (1.2-1.5 g/kg/day of protein) supplemented with omega-3 fatty acids (2-4 g/day) 1.
• Appetite stimulants like megestrol acetate (400-800 mg daily) or dexamethasone (2-4 mg daily for short courses) can improve food intake, as shown in a systematic review and meta-analysis 1.
• Exercise interventions, particularly progressive resistance training 2-3 times weekly, help preserve muscle mass.
• For pharmacological management, consider anamorelin (100 mg daily), a ghrelin receptor agonist that improves appetite and lean body mass.
• Psychosocial support is essential as depression often accompanies cachexia.
• Regular monitoring of weight, muscle mass, functional status, and nutritional parameters should guide treatment adjustments.

Importance of Early Intervention

Early intervention is critical, as cachexia becomes increasingly refractory to treatment as it progresses. The pathophysiology involves complex inflammatory processes, metabolic alterations, and anabolic resistance, which explains why multimodal therapy targeting different pathways is more effective than single interventions 1.

Classification and Management

Cachexia can be classified into precachexia, cachexia, and refractory cachexia, with different management strategies for each stage, including nutrition counseling, fortified food, oral nutritional supplements (ONS), enteral feeds, and palliative nutrition 1.

From the FDA Drug Label

The effectiveness of dronabinol capsules has been established based on studies for the treatment of anorexia associated with weight loss in patients with AIDS and nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. The appetite stimulant effect of dronabinol capsules in the treatment of AIDS-related anorexia associated with weight loss was studied in a randomized, double-blind, placebo-controlled study involving 139 patients.

The appropriate workup for cachexia is not directly addressed in the provided drug labels. However, the treatment of anorexia associated with weight loss, which is a component of cachexia, can include the use of dronabinol 2 to stimulate appetite.

• Dronabinol has been shown to be effective in increasing appetite in patients with AIDS-related anorexia associated with weight loss.
• Another option for the treatment of anorexia is megestrol acetate 3, although its use is associated with potential risks, including adrenal insufficiency and glucose intolerance. It is essential to note that cachexia is a complex condition that requires a comprehensive approach, including nutritional support and management of underlying conditions.

From the Research

Diagnosis and Workup of Cachexia

• Cachexia is a multiorgan, multifactorial, and often irreversible wasting syndrome associated with cancer and other serious, chronic illnesses, including AIDS, chronic heart failure, chronic kidney disease, and chronic obstructive pulmonary disease 4.
• The clinical consequences of cachexia are dependent on both weight loss and systemic inflammation, which accompany cachexia development 5.
• Diagnosis of cachexia is based on the loss of >5% of an individual's baseline body weight over 2-6 months, and anorexia is considered a key component of the anorexia-cachexia syndrome 6.

Treatment Options for Cachexia

• Treatment of cachexia is currently targeted to correcting the two underlying features of the condition: anorexia and metabolic disturbances 4.
• Several classes of drugs are under active development for cachexia, including drugs acting on hormone receptors or cytokine receptors, myostatin/activin pathway antagonists, beta-adrenoceptor agonists, and cannabinoids 4.
• Nonpharmacological therapy, such as nutritional support and physical exercise, is considered central to cachexia prevention and treatment 5.
• Megestrol acetate is commonly used to treat anorexia-cachexia syndrome, and its mechanism of action involves stimulation of appetite and antagonism of the metabolic effects of catabolic cytokines 6, 7, 8.
• Meta-analysis has shown that megestrol acetate improves appetite and is associated with slight weight gain in cancer, AIDS, and other underlying conditions, but higher doses are more related to weight improvement than lower doses 7.

Management of Cachexia

• Preventive strategies for cachexia have largely focused on muscle mass preservation 5.
• Different treatment options have been described, including nutritional support, neurohormonal blockade, reducing intestinal bacterial translocation, anemia and iron deficiency treatment, appetite stimulants, immunomodulatory agents, anabolic hormones, and physical exercise regimens 5.
• The optimal dose of megestrol acetate is not well defined, but it is essential to inform patients of the risks involved in taking the drug, including oedema, thromboembolic phenomena, and deaths 7.