Warr David G, Grunberg Steven M, Gralla Richard J, Hesketh Paul J, Roila Fausto, Wit Ronald de, Carides Alexandra D, Taylor Arlene, Evans Judith K, Horgan Kevin J
Princess Margaret Hospital, 610 University Avenue, Toronto, Ont., Canada M5G 2M9.
Eur J Cancer. 2005 Jun;41(9):1278-85. doi: 10.1016/j.ejca.2005.01.024.
In this work, data from two phase III studies were pooled to further evaluate the NK(1) antagonist aprepitant for prevention of cisplatin induced nausea and vomiting. One thousand and forty three patients receiving cisplatin (> or = 70 mg/m2) were randomised to receive either a control regimen (32 mg intravenous ondansetron [O] and 20 mg oral dexamethasone [D] on day 1; 8 mg D twice daily on days 2-4) or an aprepitant (A) regimen (125 mg A plus 32 mg O and 12 mg D on day 1, 80 mg A and 8 mg D once daily on days 2-3, and 8 mg D on day 4). The primary endpoint was no emesis and no rescue therapy. Potential correlations between acute and delayed emesis were assessed, as were frequency of emetic episodes by time interval and effects on nausea and quality of life as measured by the functional living index emesis (FLIE) questionnaire. In the aprepitant group, there was statistically significantly less nausea over the study period as well as higher functioning on the FLIE questionnaire in both the nausea and vomiting domains. Patients without acute emesis were more likely to have no emesis in the delayed phase. Compared with control, the aprepitant regimen improved prevention of delayed emesis by 16% points in patients without acute emesis, and by 17% points in patients with acute emesis. Among patients who did not have complete response, the frequency of emesis at various intervals over 5 days was consistently lower in patients receiving aprepitant. Analyses of this combined Phase III population further characterized the clinical profile of the aprepitant regimen, showing that delayed emesis is correlated with, but not entirely dependent on, the presence of acute emesis, and that aprepitant has a favorable effect against nausea throughout 5 days postchemotherapy. In addition, even among patients who had emesis or needed rescue therapy, aprepitant was associated with a lower frequency of these events compared with the control regimen.
在本研究中，汇总了两项III期研究的数据，以进一步评估NK(1)拮抗剂阿瑞匹坦预防顺铂所致恶心和呕吐的效果。1043例接受顺铂（≥70mg/m²）治疗的患者被随机分为两组，一组接受对照方案（第1天静脉注射32mg昂丹司琼[O]和口服20mg地塞米松[D]；第2 - 4天每天两次口服8mg D），另一组接受阿瑞匹坦（A）方案（第1天口服125mg A加32mg O和12mg D，第2 - 3天每天一次口服80mg A和8mg D，第4天口服8mg D）。主要终点为无呕吐且未接受挽救治疗。评估了急性呕吐与延迟性呕吐之间的潜在相关性，以及按时间间隔划分的呕吐发作频率，还有通过功能性生活指数呕吐（FLIE）问卷测量的对恶心和生活质量的影响。在阿瑞匹坦组中，在研究期间恶心症状在统计学上显著减轻，并且在FLIE问卷的恶心和呕吐领域功能评分更高。无急性呕吐的患者在延迟期更有可能无呕吐。与对照组相比，阿瑞匹坦方案在无急性呕吐的患者中延迟性呕吐的预防效果提高了16个百分点，在有急性呕吐的患者中提高了17个百分点。在未完全缓解的患者中，接受阿瑞匹坦治疗的患者在5天内不同时间段的呕吐频率持续较低。对这一合并的III期研究人群的分析进一步明确了阿瑞匹坦方案的临床特征，表明延迟性呕吐与急性呕吐有关，但并非完全依赖于急性呕吐的存在，并且阿瑞匹坦在化疗后5天内对恶心有良好效果。此外，即使在有呕吐或需要挽救治疗的患者中，与对照方案相比，阿瑞匹坦治疗这些事件的频率更低。
