What antiemetic is used for dose-dense Adriamycin (doxorubicin) and Cyclophosphamide (AC) chemotherapy?

From the Guidelines

**For dose-dense AC (Adriamycin/Cyclophosphamide) chemotherapy, the recommended anti-emetic regimen is:

1. Aprepitant 125 mg orally on day 1, followed by 80 mg orally on days 2 and 3
2. Dexamethasone 12 mg orally on day 1, then 8 mg orally on days 2-4
3. 5-HT3 receptor antagonist (e.g., ondansetron 8 mg orally twice daily) on day 1.** This three-drug combination is highly effective for preventing both acute and delayed nausea and vomiting associated with highly emetogenic chemotherapy like dose-dense AC, as supported by the most recent and highest quality study 1. Aprepitant is a neurokinin-1 (NK1) receptor antagonist that blocks substance P in the brain, reducing the vomiting reflex. Dexamethasone has anti-inflammatory effects and may reduce serotonin release. The 5-HT3 antagonist blocks serotonin receptors in the gastrointestinal tract and chemoreceptor trigger zone. Some key points to consider:

• The antiemetic regimen for highly emetogenic drugs, including AC combinations, typically includes aprepitant, dexamethasone, and a 5-HT3 antagonist, as recommended by guidelines 1.
• Aprepitant has been shown to augment the antiemetic activity of 5-HT3 receptor antagonists and corticosteroids for preventing both acute and delayed emesis 1.
• Proper hydration and small, frequent meals can also help manage nausea, and a rescue anti-emetic like prochlorperazine may be prescribed for breakthrough nausea.
• The optimal dose and schedule of antiemetics may vary depending on the specific chemotherapy regimen and patient factors, but the recommended regimen for dose-dense AC chemotherapy is well-established 1.

From the FDA Drug Label

A randomized, placebo-controlled, double-blind trial was conducted in the US in 67 patients receiving a cyclophosphamide-based chemotherapy regimen containing doxorubicin The first 8 mg dose of ondansetron tablets was administered 30 minutes before the start of chemotherapy, with a subsequent dose 8 hours after the first dose, followed by 8 mg of ondansetron tablets twice a day for 2 days after the completion of chemotherapy.

The antiemetic used for dose-dense Adriamycin (doxorubicin) and Cyclophosphamide (AC) chemotherapy is ondansetron.

• The recommended dosage is 8 mg administered twice a day. 2

From the Research

Antiemetic Regimens for Chemotherapy-Induced Nausea and Vomiting

• The use of a combination of a 5-HT3 receptor antagonist, dexamethasone, and aprepitant is recommended for the prophylaxis of acute and delayed emesis in patients receiving highly emetogenic chemotherapy, including dose-dense Adriamycin (doxorubicin) and Cyclophosphamide (AC) chemotherapy 3, 4.
• Aprepitant, a neurokinin-1 (NK(1)) receptor antagonist, has been shown to be effective in preventing chemotherapy-induced nausea and vomiting (CINV) when combined with a standard regimen of a corticosteroid and a serotonin 5-HT(3) receptor antagonist 4, 5.
• The addition of 3-day aprepitant to ondansetron and dexamethasone has been shown to be effective in controlling CINV in patients with diffuse large B cell lymphoma receiving 5-day cisplatin-based chemotherapy 6.
• For patients receiving high-dose chemotherapy with stem cell transplant, a combination of a 5-HT3 receptor antagonist with dexamethasone and aprepitant is recommended before chemotherapy 3, 7.

Specific Antiemetic Agents

• Olanzapine has been shown to be effective in the treatment of breakthrough nausea and vomiting, with a recommended dose of 10 mg orally daily for 3 days 3.
• Aprepitant is recommended at a dose of 125 mg orally on day 1 and 80 mg orally on days 2-4 for the prevention of CINV 4, 5, 6.