How to manage anorexia (loss of appetite) due to cancer?

Management of Cancer-Related Anorexia

Address reversible causes first, then initiate nutritional counseling with oral supplements, and consider appetite stimulants (megestrol acetate or dexamethasone) only when increased appetite is important for quality of life in patients with months-to-weeks life expectancy. 1

Initial Assessment and Nutritional Screening

• Perform nutritional assessment at tumor diagnosis and repeat at every visit to initiate intervention early before severe compromise occurs 1
• Recognize that cancer-related anorexia results from two main components: decreased nutrient intake (from tumor effects or cytokine-mediated anorexia) and metabolic alterations from systemic inflammation 1
• Understand that cytokine-induced metabolic changes prevent cachectic patients from regaining body cell mass with nutritional support alone, requiring integrated approaches beyond exogenous nutrients 1

Step 1: Address Reversible Causes

Systematically evaluate and treat underlying conditions that interfere with food intake: 1

• Pain management - uncontrolled pain suppresses appetite
• Constipation relief - causes early satiety and discomfort
• Nausea/vomiting control - use appropriate antiemetics
• Depression treatment - assess and treat with SSRIs if present 1
• Oropharyngeal candidiasis - examine oral cavity and treat fungal infections 1
• Early satiety - consider metoclopramide as a gastroprokinetic agent 1

Step 2: Nutritional Interventions

For Patients Undergoing Active Treatment

• Provide nutritional counseling with oral supplements for patients with gastrointestinal or head and neck cancers undergoing radiation, which significantly improves weight maintenance and quality of life 1
• Dietary counseling alone (without supplements) showed significant benefit for anorexia and quality of life in patients with colorectal cancer receiving radiotherapy 1

For Malnourished Patients

• If malnourished or facing >1 week of starvation and enteral nutrition is not feasible, initiate parenteral nutrition (PN) 1
• Do NOT use routine PN during chemotherapy, radiotherapy, or combined therapy in well-nourished patients 1
• For incurable patients with intestinal failure, offer long-term PN if: (1) enteral nutrition is insufficient, (2) expected survival >2-3 months, (3) PN can stabilize/improve performance status and quality of life, and (4) patient desires this support 1

Step 3: Pharmacological Appetite Stimulation

Primary Agent: Megestrol Acetate

For patients with months-to-weeks or weeks-to-days life expectancy where increased appetite is important for quality of life, megestrol acetate is the preferred appetite stimulant: 1, 2

• Efficacy: 1 in 4 patients will experience increased appetite; 1 in 12 will achieve measurable weight gain 1, 2
• Dosing: 400-800 mg/day 3
• Critical safety warning: 1 in 6 patients will develop thromboembolic phenomena and 1 in 23 will die from treatment-related complications 1, 2
• Weight gain is primarily adipose tissue rather than skeletal muscle, limiting clinical benefit 2
• Systematic review showed patients receiving megestrol acetate were 2.57 times more likely to experience appetite improvement versus placebo 2

Alternative Agent: Dexamethasone

• Consider dexamethasone (2-8 mg/day) for short-term appetite stimulation in patients with limited life expectancy due to rapid onset of action 3
• Similar appetite-stimulating effects to megestrol acetate but different toxicity profile 2

Other Options

• Olanzapine (5 mg/day) may be considered, especially for patients with concurrent nausea or anxiety 1, 3
• Mirtazapine can be useful for appetite stimulation, particularly in patients with concurrent sleep difficulties or mood disorders 3

Cannabinoids (Dronabinol): Limited Role

Cannabinoids have very limited data to support their use for cancer-related anorexia/cachexia and are NOT recommended as first-line therapy: 1, 3

• A randomized trial of cannabis extract and delta-9-tetrahydrocannabinol did NOT demonstrate benefit over placebo on appetite and quality of life 1
• FDA approval for dronabinol in AIDS-related anorexia showed statistically significant appetite improvement at 4 and 6 weeks, but this does not translate to cancer populations 4
• Major safety concern: Cannabinoid administration in elderly patients may induce delirium 3
• Megestrol acetate shows superior efficacy compared to cannabinoids 3

Step 4: Combination Therapy Approaches

For optimal outcomes, consider multimodal combination therapy: 1, 2

• A phase III trial showed superior outcomes with combination regimen including medroxyprogesterone, megestrol acetate, eicosapentaenoic acid, L-carnitine supplementation, and thalidomide versus single agents 1
• Another phase III trial demonstrated that megestrol acetate plus L-carnitine, celecoxib, and antioxidants improved lean body mass, appetite, and quality of life compared to megestrol acetate alone 1, 2

Common Pitfalls to Avoid

• Do not delay nutritional assessment - waiting until severe compromise occurs reduces chances of restoration 1
• Do not use routine PN in well-nourished patients undergoing chemotherapy or radiotherapy 1
• Do not ignore thromboembolic risk with megestrol acetate - requires regular monitoring 1, 2
• Do not use cannabinoids as first-line therapy - limited efficacy and delirium risk in elderly 1, 3
• Do not assume feeding the tumor is harmful - there is no evidence that PN has deleterious effects on outcome when clinically indicated 1
• Do not rely on nutritional support alone - cytokine-induced metabolic alterations prevent body cell mass restoration without addressing underlying inflammation 1

Monitoring Requirements

• Regular weight monitoring to assess response to interventions 2
• Assessment for thromboembolic phenomena in patients receiving megestrol acetate 2
• Cognitive monitoring in elderly patients, especially if using cannabinoids 3
• Performance status and quality of life assessment to guide continuation of interventions 1