Antiemetic Prophylaxis for Chemotherapy

Chemotherapy-induced nausea and vomiting is largely preventable, and prophylaxis must be given before the chemotherapy, not after symptoms start. Choice depends on the emetic risk of the regimen and the patient’s risk factors (age under 50, female, low alcohol intake, previous chemotherapy nausea, motion sickness, pregnancy sickness).

Emetic risk.

• High (over 90% without prophylaxis): cisplatin, anthracycline with cyclophosphamide, cyclophosphamide over 1500 mg/m2, dacarbazine.
• Moderate (30 to 90%): carboplatin, oxaliplatin, doxorubicin, cyclophosphamide 1500 mg/m2 or under, irinotecan.
• Low (10 to 30%): paclitaxel, docetaxel, gemcitabine, fluorouracil, etoposide, cetuximab.
• Minimal (under 10%): bevacizumab, vincristine, rituximab.

Timing. Acute (first 24 hours), delayed (days 2 to 5) and anticipatory. Delayed symptoms are common with cisplatin and anthracycline-cyclophosphamide.

High risk (4 drug prophylaxis).

• NK1 antagonist: aprepitant 125 mg orally on day 1, then 80 mg on days 2 and 3 (or fosaprepitant 150 mg IV on day 1).
• 5HT3 antagonist on day 1: granisetron 1 mg IV (or 2 mg orally), ondansetron 8 mg IV (or 16 mg orally), or palonosetron 250 micrograms IV.
• Dexamethasone 12 mg orally or IV on day 1, then 8 mg once daily on days 2 to 4 when given with an NK1 antagonist (without one, use 20 mg on day 1).
• Olanzapine 5 to 10 mg orally at night on days 1 to 4.

Moderate risk.

• 5HT3 antagonist plus dexamethasone 8 mg on day 1 (then 8 mg daily on days 2 and 3 if delayed nausea is likely).
• Add an NK1 antagonist for carboplatin AUC 4 or more, and for patients with extra risk factors.

Low risk. A single agent before treatment: dexamethasone 8 mg, or metoclopramide 10 mg, or a 5HT3 antagonist.

Minimal risk. No routine prophylaxis.

Breakthrough. Add a drug from another class: olanzapine 5 to 10 mg once daily, metoclopramide 10 mg every 6 to 8 hours, or haloperidol 0.5 to 1 mg every 6 to 8 hours. Lorazepam 0.5 to 1 mg for anticipatory symptoms.

Choice where NK1 antagonists are unavailable. Use 5HT3 antagonist, dexamethasone and olanzapine together for high-risk regimens.

Kidney impairment. No change for most drugs; metoclopramide reduce by 50% if eGFR under 60 mL/min.

Liver impairment. Reduce olanzapine and aprepitant dose in moderate to severe impairment; ondansetron maximum 8 mg daily in severe impairment.

Older adults. Olanzapine start at 2.5 to 5 mg; avoid metoclopramide and haloperidol in parkinsonism; watch sedation, falls and constipation.

Interactions. Aprepitant is a moderate CYP3A4 inhibitor: dexamethasone exposure rises (use the reduced dexamethasone doses), and warfarin and oral contraceptive effect is reduced. QT-prolonging drugs with ondansetron or haloperidol: check ECG and electrolytes. Metoclopramide with olanzapine or haloperidol: extrapyramidal reactions.

Safety. Ondansetron causes constipation and QT prolongation (maximum single IV dose 16 mg). Dexamethasone raises glucose and causes insomnia; give in the morning. Avoid olanzapine in uncontrolled diabetes unless glucose is monitored.

Pregnancy and breastfeeding. Ondansetron, metoclopramide and chlorphenamine are used in pregnancy when benefit outweighs risk; aprepitant data are limited. Avoid breastfeeding during chemotherapy.

Regional. Aprepitant and palonosetron are often costly or unavailable in East Africa, so protect access to ondansetron, dexamethasone, metoclopramide and olanzapine. Check for malaria before attributing vomiting to chemotherapy in febrile patients.

Assess. Ask about nausea, vomiting, oral intake and constipation at each cycle; use a simple 0 to 10 scale.

Adjust. Step up the risk category by one level for the next cycle if control fails.

Complications. Dehydration, hypokalaemia, hypomagnesaemia, hyponatraemia (check electrolytes after repeated vomiting) and weight loss.

Escalate. Refer or admit for vomiting lasting over 24 hours, inability to take oral fluids or drugs, or signs of obstruction or raised intracranial pressure. Use parenteral hydration and IV antiemetics.