8608 Background: Olanzapine has been shown to be a safe and effective agent for the prevention of CINV in chemotherapy naïve cancer patients. Palonosetron has been approved for the prevention of acute CINV and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy (MEC). METHODS: A phase II trial was performed for the prevention of CINV in chemotherapy naïve patients using the combination of olanzapine and palonosetron. The regimen was 10 mg of oral olanzapine, 0.25 mg of intravenous palonosetron, and dexamethasone (20 mg for highly emetogenic and 8 mg for moderately emetogenic chemotherapy) on the day of chemotherapy, day 1, and 10 mg/day of oral olanzapine alone on days 2-4 after chemotherapy. Forty patients (median age 60 yrs, range 38-84; 22 females; ECOG PS 0,1) consented to the protocol and all were evaluable. RESULTS: The percentage of patients with a complete response (CR) (no emesis, no rescue) was 100% for the acute period (24 h post chemotherapy), 75% for the delayed period (days 2-5 post chemotherapy), and 75% for the overall period (0-120 h) for eight patients receiving highly emetogenic chemotherapy (HEC) (cisplatin > 70 mg/m(2)). CR was 97% for the acute period, 75% for the delayed period, and 72% for the overall period in 32 patients receiving MEC (doxorubicin, >50mg/m(2)). In the patients receiving HEC, the percentage of patients without nausea (0, scale 0-10, M. D. Anderson Symptom Inventory) was 100% in the acute period, 50% in the delayed period, and 50% in the overall period. In patients receiving MEC, the percentage without nausea was 100% in the acute period, 78% in the delayed period, and 78% in the overall period. There were no Grade 3 or 4 toxicities and no significant pain, fatigue, disturbed sleep, memory changes, dyspnea, lack of appetite, drowsiness, dry mouth, mood changes or restlessness experienced by the patients. CR and control of nausea in subsequent cycles of chemotherapy (35 patients, cycle 2; 31 patients cycle 3; 23 patients, cycle 4) were equal to or greater than cycle one. CONCLUSIONS: The combination of olanzapine and palonosetron with dexamethasone given only on the day of chemotherapy was safe and highly effective in controlling acute and delayed CINV in patients receiving HEC and MEC. No significant financial relationships to disclose.