Efficacy of a 1-day 3-drug antiemetic regimen for prevention of acute and delayed nausea and vomiting induced by moderately emetogenic chemotherapy

Abstract

9111 Background: Serotonin antagonists, NK-1 antagonists (NKA) and corticosteroids (C) have all shown efficacy against chemotherapy-induced nausea and vomiting. However these agents are commonly used in cumbersome and inconvenient multiple day regimens that can also raise questions of compliance. Palonosetron is a serotonin antagonist with a 40 hour half-life, requiring only one dose for several days of exposure. Single high doses of NKA and C can also be used to simulate drug exposures achieved with a multiple day regimen. We have therefore evaluated a 1-day 3-drug antiemetic regimen for 5 day efficacy against moderately emetogenic chemotherapy. Methods: Patients with solid tumors receiving their first cycle of cyclophosphamide and/or doxorubicin were eligible to receive a single pre-treatment dose of palonosetron 0.25 mg IV/dexamethasone 20 mg PO/aprepitant 285 mg PO. Nausea and vomiting were evaluated over the following 5 days with a patient diary including vomiting episodes, use of rescue medication, and daily nausea visual analogue scale (VAS). Patients were urged to begin rescue medication for nausea, vomiting, or related discomfort. Endpoints included Complete Response (CR) (no emesis or rescue), No Emesis (NE), and No Significant Nausea (NSN) (VAS<25) during the acute period (A) (Day 1), the delayed period (D) (Days 2–5), and the overall period (O) (Days 1–5). Adverse events were recorded and tabulated for at least 14 days. Results: 32 of 40 planned patients have been entered on study. 31 women and 1 man with breast cancer receiving adjuvant chemotherapy with median age 52 years (range 34–74) have been treated and all are evaluable. CR for A/D/O was 78%/59%/50%. However NE for A/D/O was 100%/97%/97%, and NSN for A/D/O was 75%/62%/56%. Only 8 patients had more than one day of Significant Nausea. The most common treatment-related adverse events were fatigue and mild headache. Conclusions: A 1-day 3-drug antiemetic regimen is feasible and effective, and should be tested against a multiple day standard antiemetic regimen. [Table: see text]