e20536 Background: Patients may experience breakthrough nausea and vomiting (BNV) despite adequate prophylaxis for chemotherapy-induced nausea and vomiting (CINV). BNV presents a difficult situation as treatment of ongoing nausea and vomiting is challenging. We investigated three different drug classes for the treatment of BNV: phenothiazines (prochlorperazine)(Pro), dopamine-serotonin receptor antagonists (metoclopramide) (Meto), and a corticosteroid-thiobenzodiazepine combination (dexamethasone plus atypical antipsychotic olanzapine) (Dex-Olan). METHODS: Adult patients, receiving moderately emetogenic chemotherapy and CINV prophylaxis with a 5-hydroxytryptamine-3 receptor antagonist and Dex pre-chemotherapy and Dex post-chemotherapy according to ASCO guidelines, who experienced BNV during the five days post-chemotherapy were randomized to receive Pro, 10 mg IV, and 10 mg, po, bid for three days; Meto, 20 mg IV, and 10 mg, po, bid for 3 days; or Dex, 20 mg IV and Olan, 5 mg, po, bid for three days. All patients also received at least one liter of IV fluids during the IV phase of their treatment. Patients were excluded if they had undergone rescue therapy with any of the study agents. Beginning with the first day of treatment for BNV (day 1) and daily through day 5, patients recorded episodes of vomiting/retching, nausea, other symptoms utilizing the M.D. Anderson Symptom Inventory, and the utilization of any additional rescue therapy. One hundred six patients (median age 61, range 37 - 85, 60 males, ECOG performance status ≤ 2) consented to the protocol and 100 were evaluable. RESULTS: A complete response (no emesis, no additional rescue) for the five days post-initiation of BNV treatment was recorded for 7 of 35 patients (20%) in the Pro regimen, 12 of 33 patients (36%) receiving the Meto regimen, and 21 of 32 patients (66%) receiving the Dex-Olan regimen. There were no Grade III or IV treatment related toxicities. CONCLUSION: The combination of Dex-Olan was an effective treatment for BNV and was significantly more effective than Pro or Meto alone. No significant financial relationships to disclose.