What is the treatment for cachexia?

Treatment of Cachexia

For cancer-related cachexia, clinicians may offer a short-term trial of megestrol acetate or corticosteroids (such as dexamethasone) to improve appetite and potentially stabilize weight, though no pharmacologic agent is FDA-approved or strongly endorsed for improving cachexia outcomes. 1

Initial Assessment and Non-Pharmacologic Management

Nutritional Counseling

• Refer patients to a registered dietitian for assessment and counseling focused on high-protein, high-calorie, nutrient-dense foods and practical feeding advice 1
• Nutritional intervention alone does not significantly affect weight gain or energy intake but may improve quality of life aspects including emotional functioning, dyspnea, and hunger 1
• Avoid enteral tube feeding or parenteral nutrition outside clinical trials, as these do not improve cachexia outcomes and may increase suffering near end of life 1
• A short-term trial of parenteral nutrition may be considered only in highly select patients with reversible bowel obstruction, short bowel syndrome, or malabsorption who are otherwise reasonably fit 1

Address Reversible Causes

• Treat oropharyngeal candidiasis, depression, pain, constipation, and nausea/vomiting that interfere with food intake 1
• Use metoclopramide for early satiety 1

Exercise Interventions

• Exercise may enhance muscle protein synthesis, attenuate catabolic effects, and modulate inflammation 1
• Supervised rehabilitation programs may improve skeletal muscle function and fatigue, particularly in heart failure patients with cachexia 1
• No formal recommendation can be made for exercise outside clinical trials due to insufficient evidence 1

Pharmacologic Management

First-Line Pharmacologic Options

Progesterone Analogs (Megestrol Acetate)

• Approximately 1 in 4 patients will experience increased appetite and 1 in 12 will have weight gain 1, 2
• Critical caveat: 1 in 6 patients will develop thromboembolic phenomena and 1 in 23 will die from treatment-related complications 1
• Weight gain is predominantly fat rather than lean muscle mass 1
• Consider for patients with months-to-weeks life expectancy when increased appetite is important for quality of life 1

Corticosteroids (Dexamethasone)

• Offers similar appetite improvement to megestrol acetate with faster onset of action 2
• May also help with fatigue 2
• Appropriate for short-term trials in patients with shorter life expectancy 1, 2
• Weight gain is predominantly fat rather than muscle 1

Alternative Pharmacologic Options

Cannabinoids (Dronabinol)

• Limited evidence for cancer-related cachexia; randomized trials showed no benefit over placebo for appetite and quality of life 1
• In comparative trials, megestrol acetate was superior (75% vs 49% weight gain; 11% vs 3% appetite improvement) 1
• FDA-approved for AIDS-related anorexia but not cancer cachexia 3
• May cause delirium in elderly patients 1
• Dosing typically starts at 2.5 mg twice daily, with potential reduction to once daily if side effects occur 3

Olanzapine

• May be considered for patients with concurrent nausea/vomiting 1, 2
• Causes weight gain as a side effect, though evidence for cachexia treatment is limited 2

Combination Therapy Approach

Multimodal regimens show superior outcomes compared to single agents:

• A phase III trial demonstrated that combination therapy (medroxyprogesterone + megestrol acetate + eicosapentaenoic acid + L-carnitine + thalidomide) was superior to single agents 1
• Another phase III trial showed that megestrol acetate plus L-carnitine, celecoxib, and antioxidants improved lean body mass, appetite, and quality of life compared to megestrol acetate alone 1
• Combination approaches are more likely to be successful given the multifactorial pathogenesis of cachexia 4, 5

Treatment Timing and Patient Selection

Early Intervention Principle

• Intervention is more likely effective when given early, before pronounced metabolic abnormalities produce anabolic resistance 1
• Evidence of anabolic resistance in advanced cachexia suggests focusing on prevention rather than attempting to regain lost muscle 1
• The phase of active anti-cancer therapy offers a window of opportunity for intervention when tumor control is achieved 1

Life Expectancy-Based Approach

Years to Months:

• Focus on treating underlying cancer, nutritional counseling, and addressing reversible causes 1
• Consider appetite stimulants if anorexia is prominent 1

Months to Weeks:

• Consider short-term trials of megestrol acetate or corticosteroids if appetite is important for quality of life 1
• Shift focus toward maintaining quality of life rather than prolonging life 1

Weeks to Days:

• Discontinue enteral or parenteral nutrition 1
• Focus on treating dry mouth and thirst rather than aggressive nutritional support 1
• Provide family education about alternate ways to provide comfort 1

Heart Failure-Specific Cachexia

• Cachexia affects 10-15% of chronic heart failure patients and is defined as involuntary non-edematous weight loss of 6% of total body weight within 6-12 months 1
• Mortality of cachectic heart failure patients exceeds that of most malignant diseases 1
• Treatment has not been established as a standard goal in heart failure cachexia 1
• Options include hypercaloric feeding, appetite stimulants, exercise training, and anabolic agents (insulin, anabolic steroids) 1

Critical Caveats

• No FDA-approved medications exist for cancer cachexia 1
• Evidence quality for all interventions remains low to intermediate 1
• Clinicians may choose not to offer medications for cachexia treatment given insufficient evidence 1
• Avoid fad diets and unproven extreme diets 1
• Aggressive nutritional support near end of life can increase patient suffering 1
• Single-agent therapy is unlikely to be completely successful given the multifactorial pathogenesis 4, 5