Aprepitant as salvage antiemetic therapy in breast cancer patients receiving doxorubicin and cyclophosphamide (AC)

Abstract

8618 Background: Aprepitant (APR), a neurokinin-1 receptor antagonist, has efficacy in the prevention of nausea and vomiting (NV) in breast cancer (BC) patients (pts) receiving doxorubicin (A) and cyclophosphamide (C) (JCO 2005, 23:2822). Nevertheless, many pts continue to receive only 5-hydroxytryptamine antagonists and dexamethasone (doublet therapy) during cycle 1 of AC. APR is often used as a salvage treatment, with anecdotal reports of improved outcome. We sought to prospectively evaluate this issue in a phase II trial. Methods: Design: multicenter study funded by an unrestricted grant from Merck. Eligibility: BC pts receiving their first cycle of A (≤ 60 mg/m2) and C (≥ 500 mg/m2) on day (d) 1. Antiemetics: ondansetron 8mg IV/PO, or dolasetron 100 mg IV/PO, or granisetron 1 mg IV or 2 mg PO on d 1; and dexamethasone (dex) 8–10 mg IV/PO d 1 and 4 mg PO bid d 2–3. Pts without complete control (no emesis, nausea, or rescue antiemetics) during cycle 1 could continue to cycle 2.During cycle 2, pts again received AC and identical antiemetics (except dex only 4 mg qd d 2–3) plus APR 125 mg PO d 1 and 80 mg PO d 2–3. Data on nausea (4-point scale), emesis and rescue was collected with a pt-report diary. Primary end point: proportion of pts with complete control (CC) during the 120-hours after chemotherapy. Secondary endpoints included acute (< 24 hrs), delayed (24–120 hrs) CC and complete response (no emesis or rescue) Results: Pts: total (47), female (47), eligible (46), analyzed (42), still on study (4). Median age: 49 yrs. CC during cycle 1: 8 pts (19%). Thirty-four pts continued to cycle 2. During cycle 2, 7 pts (21%)(95% CI 9–38%) achieved CC and 13 pts (38 %) complete response (CR) for the 120-hour study period. Acute CR and delayed CR rates for cycles 1 and 2 were 32%(11 pts) vs 68% (23 pts) (p=0.01) and 12%(4 pts) vs 44% (15 pts) (p=0.02) respectively. No emesis rates were 38 vs 79 % during cycles 1 and 2 respectively(p=0.02). The proportion of pts with no nausea or severe nausea for cycles 1 and 2 were 0 vs 21% and 12 vs 3 % respectively. Conclusions: The addition of APR to standard doublet therapy improves antiemetic outcome in BC pts receiving AC who failed to achieve CC during cycle 1 with standard doublet therapy alone. Improvement is seen in the control of emesis and nausea. APR was well tolerated. [Table: see text]