A 38-year-old woman undergoing chemotherapy with cisplatin for ovarian cancer develops severe nausea and vomiting on day 1 of treatment despite premedication with ondansetron 8 mg IV. The vomiting is refractory and interferes with oral intake. What is the most appropriate next step in management?

Explanation

## Chemotherapy-Induced Nausea and Vomiting (CINV) Management ### Classification of CINV Cisplatin is a **highly emetogenic** chemotherapy agent (>90% risk of CINV without prophylaxis). The vomiting occurring within 24 hours is **acute CINV**. ### Rationale for Combination Therapy **Key Point:** Highly emetogenic chemotherapy requires **multimodal antiemetic prophylaxis** targeting multiple receptor pathways simultaneously. The optimal regimen for cisplatin-induced CINV includes: | Component | Agent | Mechanism | Timing | | --- | --- | --- | --- | | **5-HT₃ antagonist** | Ondansetron 8 mg IV | Blocks serotonin at CTZ | Pre-chemotherapy | | **NK1 antagonist** | Aprepitant 125 mg PO | Blocks substance P in chemoreceptor trigger zone | Day 1, 2, 3 | | **Corticosteroid** | Dexamethasone 8 mg IV/PO | Reduces inflammatory mediators | Days 1–4 | | **Optional: Benzodiazepine** | Lorazepam | Anxiolytic + amnestic | PRN | **High-Yield:** The **5-HT₃ antagonist monotherapy is insufficient** for highly emetogenic agents. Adding a **corticosteroid + NK1 antagonist** significantly improves control of acute and delayed CINV. ### Why This Patient Needs Escalation - Ondansetron monotherapy (even at standard dose) fails in ~40% of cisplatin recipients - Refractory vomiting on day 1 indicates need for **combination therapy**, not dose escalation of the same agent - Aprepitant + dexamethasone are **guideline-recommended additions** for highly emetogenic chemotherapy **Clinical Pearl:** Delayed CINV (days 2–5) is even more common than acute CINV with cisplatin; prophylaxis must continue beyond day 1. [cite:KD Tripathi 8e Ch 47]