Treatment of Chemotherapy-Induced Nausea and Vomiting
For chemotherapy-induced nausea and vomiting, use a risk-stratified prophylactic approach with combination antiemetic therapy starting 30-60 minutes before chemotherapy, selecting from 5-HT3 receptor antagonists, dexamethasone, and NK1 receptor antagonists (aprepitant) based on the emetogenic potential of the chemotherapy regimen. 1
Risk Stratification and Prophylactic Regimens
High Emetogenic Risk Chemotherapy (e.g., Cisplatin ≥50 mg/m²)
Triple therapy is mandatory:
- Aprepitant 125 mg PO on day 1, followed by 80 mg PO on days 2-3 1
- Dexamethasone 12 mg PO or IV on days 1-4 1
- Palonosetron 0.25 mg IV on day 1 (preferred 5-HT3 antagonist) 1
- Alternative: Ondansetron 24 mg PO as single dose or 8 mg IV 2
This combination achieves complete response (no emetic episodes) in approximately 66% of patients receiving highly emetogenic chemotherapy 2. When using aprepitant with corticosteroids, reduce the dexamethasone dose by 50% due to CYP3A4 interactions 1.
Moderate Emetogenic Risk Chemotherapy (e.g., Cyclophosphamide/Doxorubicin)
Dual or triple therapy depending on patient factors:
- 5-HT3 antagonist: Ondansetron 8 mg IV or 16-24 mg PO 3, 2
- Dexamethasone 8 mg IV single dose before chemotherapy 3
- Aprepitant 125 mg PO day 1, then 80 mg PO days 2-3 (in select patients) 1
For cyclophosphamide-based regimens, ondansetron 8 mg administered 30 minutes before chemotherapy, with a subsequent dose 8 hours later, followed by 8 mg twice daily for 2 days after completion, was significantly more effective than placebo 2.
Low Emetogenic Risk Chemotherapy
Single antiemetic agent is sufficient:
Timing and Route of Administration
Administer all prophylactic antiemetics 30-60 minutes before chemotherapy initiation 4, 5. Oral and IV formulations have equivalent efficacy for prophylaxis, but switch to IV administration immediately if breakthrough nausea or vomiting occurs 4, 3.
Management of Delayed Nausea and Vomiting (>24 hours post-chemotherapy)
Continue antiemetic coverage for 1-5 days after chemotherapy:
- Continue aprepitant 80 mg PO on days 2-3 if used on day 1 1
- Dexamethasone 8 mg PO twice daily on days 2-3 3
- Add metoclopramide 20-30 mg PO three to four times daily on days 2-4 if symptoms persist 3
Corticosteroids for delayed emesis are given twice daily, unlike the once-daily dosing for acute prophylaxis 4.
Breakthrough and Refractory Nausea and Vomiting
When prophylaxis fails, escalate therapy aggressively:
- Switch to IV administration of all antiemetics 4, 5
- Ondansetron 8 mg IV (not oral) for active vomiting 3
- Add metoclopramide 10-40 mg IV every 4-6 hours as a dopamine antagonist 3
- Add or increase dexamethasone to 20 mg IV if not already prescribed 3
- Consider olanzapine 10 mg PO daily for 3 days 6, 7
For refractory cases, consider switching to a different 5-HT3 antagonist, as substances within the same class have comparable efficacy but individual patient response may vary 4, 1.
Anticipatory Nausea and Vomiting
Prevent with anxiolytic and behavioral interventions:
- Lorazepam 0.5-2 mg PO, IV, or sublingual 30 minutes before chemotherapy 1, 3
- Incorporate behavioral techniques alongside pharmacologic management 3
Anticipatory symptoms occur days to hours before chemotherapy and are best prevented by ensuring excellent control during prior cycles 4, 8.
Special Considerations and Pitfalls
Multiple-Day Chemotherapy Regimens
Use the acute prophylaxis protocol on all chemotherapy days, followed by delayed prophylaxis for 1-2 days after the final chemotherapy dose 5, 7.
High-Dose Chemotherapy with Stem Cell Transplant
Use full doses of 5-HT3 antagonist IV plus dexamethasone plus aprepitant (125 mg day 1,80 mg days 2-4), with consideration of adding olanzapine 6, 7.
QT Prolongation Risk
High-dose ondansetron (32 mg IV single dose) has been associated with QT interval prolongation and is not recommended 1. The 24 mg oral dose or 8 mg IV dose are preferred 2.
Hepatic Impairment
In patients with severe hepatic impairment (Child-Pugh ≥10), ondansetron clearance is reduced 2-3 fold with half-life increasing to 20 hours; dose adjustment may be necessary 2.
Differential Diagnosis to Exclude
Before attributing symptoms solely to chemotherapy, rule out other causes: radiotherapy, infection, metabolic disorders, electrolyte disturbances, constipation, gastrointestinal obstruction, brain/liver/bone metastases, and other emetogenic medications (opioids, antibiotics, antifungals) 4.
Key Principle: Prevention Over Treatment
Good control of acute nausea and vomiting (first 24 hours) strongly predicts control of delayed emesis 8. Conversely, protection failure during the first 24 hours has high predictive value for delayed emesis in the same cycle 8. Therefore, aggressive prophylaxis matched to chemotherapy emetogenicity is essential from the outset.