Overview
Definition:
Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of cancer treatment, significantly impacting a child's quality of life and treatment adherence
It encompasses both acute (within 24 hours) and delayed (24-120 hours post-chemotherapy) phases, and can be anticipatory (occurring before treatment).
Epidemiology:
The incidence of CINV in children varies widely depending on the emetogenicity of the chemotherapy regimen, patient age, prior CINV experience, and genetic predisposition
Highly emetogenic chemotherapy can affect up to 90% of pediatric patients without prophylaxis
CINV is a leading cause of dose reduction or discontinuation of chemotherapy, affecting treatment efficacy.
Clinical Significance:
Effective management of CINV in pediatric oncology is paramount for maintaining nutritional status, improving adherence to treatment, reducing hospitalizations, and enhancing the overall well-being and psychological state of the child and their family
Understanding evidence-based antiemetic protocols is crucial for all pediatric residents preparing for board examinations.
Risk Stratification
Emetogenicity Classification:
Chemotherapeutic agents are classified based on their emetogenic potential into low, moderate, high, and very high categories
This classification guides antiemetic prophylaxis strategies
For example, cisplatin, cyclophosphamide, and doxorubicin are commonly used in pediatric regimens and are associated with high emetogenicity.
Patient Factors:
Age, sex, previous CINV experience, genetic factors (e.g., ABCB1 gene polymorphisms), concomitant medications, and psychosocial factors can influence an individual's risk of developing CINV
Younger children may have different responses compared to adolescents.
Treatment Related Factors:
Dose and schedule of chemotherapy, route of administration (IV vs
oral), combination chemotherapy regimens, and concurrent radiotherapy can all influence the risk and severity of CINV.
Pathophysiology
Central Mechanisms:
The chemoreceptor trigger zone (CTZ) in the area postrema and the nucleus tractus solitarius (NTS) are key areas involved in mediating CINV
Serotonin (5-HT3), dopamine (D2), histamine (H1), acetylcholine (muscarinic), and substance P/neurokinin-1 (NK1) receptors play critical roles.
Peripheral Mechanisms:
Enterochromaffin cells in the gastrointestinal mucosa release serotonin, which stimulates vagal afferent fibers, leading to CINV
Other neurotransmitters and local mediators are also involved.
Pediatric Considerations:
While the basic mechanisms are similar, developmental differences in receptor expression and neurotransmitter systems may contribute to variations in CINV response between pediatric and adult populations
Research is ongoing to elucidate these specific pediatric nuances.
Pharmacological Management
Serotonin Receptor Antagonists:
Examples include ondansetron and granisetron
These are highly effective for acute CINV
For very high emetogenic chemotherapy, they are typically used in combination with NK1 receptor antagonists
Standard pediatric dosing for ondansetron is typically 0.15 mg/kg/dose IV every 8 hours or 3 times daily.
Nk1 Receptor Antagonists:
Aprepitant is the most commonly used NK1 receptor antagonist
It is highly effective for both acute and delayed CINV, especially when combined with 5-HT3 antagonists and corticosteroids
Pediatric dosing varies by age and regimen, often involving weight-based calculations and different formulations (capsules, oral suspension).
Corticosteroids:
Dexamethasone is a cornerstone of antiemetic prophylaxis, particularly for delayed CINV, and also has synergistic effects with 5-HT3 and NK1 antagonists
It is typically given intravenously or orally, with doses adjusted for weight and age.
Dopamine Receptor Antagonists:
Antipsychotics like prochlorperazine and haloperidol can be used as second-line agents or for breakthrough CINV, particularly when other agents are insufficient
Careful monitoring for side effects like extrapyramidal symptoms is important.
Other Agents:
Cannabinoids (e.g., nabilone) may be considered in refractory CINV, but their use in pediatric patients requires careful risk-benefit assessment due to potential central nervous system side effects
Olanzapine has shown efficacy and is increasingly used in pediatric protocols.
Prophylactic And Treatment Protocols
Highly Emetogenic Chemotherapy:
A combination of a 5-HT3 antagonist, an NK1 receptor antagonist, and a corticosteroid (e.g., dexamethasone) is recommended
Oral aprepitant or intravenous fosaprepitant can be used in children
Prophylaxis should begin prior to chemotherapy administration.
Moderately Emetogenic Chemotherapy:
A combination of a 5-HT3 antagonist and a corticosteroid is generally recommended
An NK1 antagonist may be added for patients at higher risk or those receiving specific regimens.
Low To Minimally Emetogenic Chemotherapy:
A single antiemetic agent (e.g., 5-HT3 antagonist) or scheduled oral antiemetics may be sufficient
Rescue medication should be available.
Breakthrough Cinv:
If CINV occurs despite prophylaxis, rescue antiemetics from a different class or with a different mechanism of action should be administered
This may include agents like olanzapine, haloperidol, or prochlorperazine, based on clinical judgment and patient age.
Key Points
Exam Focus:
DNB and NEET SS exams will test knowledge of current pediatric CINV guidelines, risk stratification, and the specific antiemetic agents and their combinations for different emetogenic chemotherapy regimens
Dosing, routes of administration, and common side effects are also important.
Clinical Pearls:
Always initiate prophylaxis before chemotherapy
Tailor regimens to the emetogenic potential of the specific drugs
Engage with the child and family to assess effectiveness and manage breakthrough symptoms promptly
Consider the psychological impact of CINV and provide reassurance and support.
Common Mistakes:
Underestimating the emetogenic potential of certain regimens
Inadequate combination therapy for highly emetogenic chemotherapy
Failure to provide adequate prophylaxis for delayed CINV
Inappropriate choice of rescue medication for breakthrough symptoms.