What are the appetite stimulants used in children with cancer?

Appetite Stimulants in Pediatric Cancer Patients

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Primary Appetite Stimulant Options

Cyproheptadine hydrochloride is the first-line appetite stimulant for children with cancer-related cachexia, demonstrating safe and effective weight gain with minimal side effects. 1

Cyproheptadine (First-Line Agent)

• Efficacy in pediatric oncology: In a study of 70 children with cancer-related cachexia, 76% (50/66 evaluable patients) responded to cyproheptadine with an average weight gain of 2.6 kg and mean weight-for-age z-score improvement of 0.35 (P=0.001) after 4 weeks 1

• Safety profile: The most commonly reported side effect is drowsiness, making it significantly safer than alternatives like megestrol acetate which carries risks of thromboembolic events, edema, and adrenal suppression 2, 1

• Dosing approach: Start cyproheptadine and evaluate response after 4 weeks of treatment 1

• Evidence limitations: The French National Federation of Cancer Centres notes only Level C evidence for cyproheptadine in cancer patients, recommending its use primarily in clinical trials for adult cancer cachexia 2

Megestrol Acetate (Second-Line Agent)

• Use after cyproheptadine failure: Reserve megestrol acetate for patients who do not respond to cyproheptadine after 4 weeks 1

• Efficacy in non-responders: Among 16 children who failed cyproheptadine, 5 of 6 who completed 4 weeks of megestrol acetate responded with average weight gain of 2.5 kg 1

• Significant adverse effects: One patient developed low cortisol levels and hyperlipidemia, highlighting the need for monitoring 1

• Adult guideline support: The French National Federation of Cancer Centres recommends megestrol acetate for anorexia and weight loss in cancer patients (Level B1 evidence), though these guidelines focus on adults 3

Agents NOT Recommended

Corticosteroids

• Adult evidence only: Corticosteroids are appetite stimulants with Level B1 evidence in adult cancer patients, but optimal dosing and scheduling remain undefined 3

• Lack of pediatric data: No specific evidence supports corticosteroid use as appetite stimulants in pediatric cancer populations in the provided literature

Dronabinol

• FDA indication: Approved for anorexia associated with weight loss in adult AIDS patients, not specifically for pediatric cancer cachexia 4

• Pediatric use concerns: FDA labeling indicates pediatric use has not been adequately studied 4

Hydrazine Sulphate

• Not an appetite stimulant: Level A evidence demonstrates hydrazine sulphate lacks appetite-stimulating effects 3

Clinical Algorithm for Pediatric Cancer Cachexia

Step 1: Nutritional Assessment

• Anthropometric measurements: Weight, height, weight-for-age z-scores 1, 5
• Laboratory indices: Prealbumin and serum leptin levels 1
• Clinical observation: Assess for treatment side effects affecting intake 6, 5
• Dietary assessment: Evaluate actual food intake patterns 5
• Psychosocial evaluation: Include family and child (age 6+) in assessment 6, 5

Step 2: Initial Intervention

• Dietetic and oral nutritional management first: Implement before or alongside appetite stimulants 3
• Start cyproheptadine: Initiate as first-line pharmacologic appetite stimulant 1
• Monitor for drowsiness: Primary side effect to counsel families about 1

Step 3: Response Evaluation at 4 Weeks

• Measure weight gain: Target average gain of 2-3 kg 1
• Reassess z-scores: Look for improvement in weight-for-age metrics 1
• Check laboratory markers: Repeat prealbumin and leptin levels 1

Step 4: Management of Non-Responders

• Switch to megestrol acetate: For patients failing cyproheptadine after 4 weeks 1
• Monitor for adverse effects: Check cortisol levels and lipid profiles 1
• Continue for 4 weeks: Evaluate response with same metrics 1

Critical Considerations

Multifactorial Nature of Cancer Cachexia

• Direct tumor effects: Increased metabolic rate, circulating anorexigenic peptides, gut involvement 7
• Metabolic alterations: Increased whole body protein breakdown, lipolysis, and gluconeogenesis 7
• Cytokine involvement: Tumor necrosis factor, interleukin-1, and interleukin-6 contribute to cachexia 7
• Treatment side effects: Chemotherapy and radiation cause nausea, vomiting, mucositis affecting intake 6, 7

Impact on Clinical Outcomes

• Treatment tolerance: Malnutrition leads to intolerance of chemotherapy and radiotherapy 6, 7
• Infection risk: Nutritionally depleted patients have increased local and systemic infections 7
• Survival outcomes: Nutritional status influences overall survival and event-free survival 6
• Quality of life: Adequate nutrition is essential for maintaining quality of life during treatment 6

Family-Centered Approach

• Parental perception accuracy: Parents have realistic perceptions of their child's food intake and recognize reasons for poor intake that staff may miss 8
• Parental distress: The responsibility of getting the child to eat is distressing for many parents 8
• Individual coping mechanisms: Each family requires unique support strategies 8
• Continuous support needed: Parents need ongoing support to serve an optimal role in nutritional care 8

Common Pitfalls to Avoid

• Delaying intervention: Nutritional status is a modifiable prognostic factor requiring timely intervention 6
• Using adult guidelines uncritically: Most appetite stimulant guidelines focus on adult cancer patients; pediatric evidence is limited 3
• Neglecting monitoring: Regular nutritional monitoring should occur at diagnosis, during treatment, and during follow-up 6
• Overlooking psychosocial factors: Treatment-related anxiety and family dynamics significantly impact eating patterns 5, 8