Poli-Bigelli Sergio, Rodrigues-Pereira Jose, Carides Alexandra D, Julie Ma Guoguang, Eldridge Krista, Hipple Anita, Evans Judith K, Horgan Kevin J, Lawson Francesca
Instituto de Oncologia Hematologia, Universidad Central de Venezuela, Caracas, 1050 Venezuela.
Cancer. 2003 Jun 15;97(12):3090-8. doi: 10.1002/cncr.11433.
Aprepitant is a novel neurokinin 1 (NK(1)) antagonist that has been shown to improve control of chemotherapy-induced nausea and vomiting (CINV) when added to a standard antiemetic regimen of a 5-hydroxytriptamine-3 antagonist plus a corticosteroid. The authors sought to evaluate further the efficacy and tolerability of aprepitant plus standard therapy in a large clinical trial.
This was a multicenter, randomized, double-blind, placebo-controlled, parallel-groups, Phase III study. Patients with cancer who were scheduled to receive treatment with high-dose cisplatin chemotherapy were randomized to receive 1 of 2 treatment regimens; the standard therapy group received intravenous ondansetron 32 mg and oral dexamethasone 20 mg on Day 1, and oral dexamethasone 8 mg twice daily on Days 2-4. The aprepitant group received oral aprepitant 125 mg, intravenous ondansetron 32 mg, and oral dexamethasone 12 mg on Day 1; oral aprepitant 80 mg and oral dexamethasone 8 mg once daily on Days 2-3; and oral dexamethasone 8 mg on Day 4. Patients recorded episodes of emesis, use of rescue therapy, and severity of nausea in a diary. A modified intent-to-treat approach was used to analyze the efficacy data. The primary endpoint was complete response (no emesis and no rescue therapy) during the 5-day period postcisplatin. Treatment comparisons were made using logistic regression models, and reported adverse events and physical and laboratory assessments were used to assess tolerability.
A total of 523 patients were evaluated for efficacy, and 568 patients were evaluated for safety. During the 5 days after chemotherapy, the percentages of patients who achieved a complete response were 62.7% in the aprepitant group (163 of 260 patients) versus 43.3% in the standard therapy group (114 of 263 patients; P < 0.001). For Day 1, the complete response rates were 82.8% for the aprepitant group and 68.4% for the standard therapy group (P < 0.001); for Days 2-5, the complete response rates were 67.7% in the aprepitant group and 46.8% in the standard therapy group (P < 0.001). The overall incidence of adverse events was similar between the 2 treatment groups (72.8% in the aprepitant group [206 of 283 patients] and 72.6% in the standard therapy group [207 of 285 patients]) as were rates of serious adverse events, discontinuations due to adverse events, and deaths.
In patients with cancer who are receiving high-dose cisplatin-based chemotherapy, therapy consisting of aprepitant (125 mg on Day 1 and 80 mg on Days 2-3) plus a standard regimen of ondansetron and dexamethasone provided superior antiemetic protection compared with standard therapy alone and was generally well tolerated.
阿瑞匹坦是一种新型神经激肽1（NK(1)）拮抗剂，已证明在5-羟色胺-3拮抗剂加皮质类固醇的标准止吐方案基础上添加阿瑞匹坦，可改善化疗引起的恶心和呕吐（CINV）的控制。作者试图在一项大型临床试验中进一步评估阿瑞匹坦加标准疗法的疗效和耐受性。
这是一项多中心、随机、双盲、安慰剂对照、平行组III期研究。计划接受高剂量顺铂化疗的癌症患者被随机分配接受2种治疗方案中的1种；标准治疗组在第1天接受静脉注射昂丹司琼32mg和口服地塞米松20mg，在第2 - 4天接受口服地塞米松8mg，每日2次。阿瑞匹坦组在第1天接受口服阿瑞匹坦125mg、静脉注射昂丹司琼32mg和口服地塞米松12mg；在第2 - 3天接受口服阿瑞匹坦80mg和口服地塞米松8mg，每日1次；在第4天接受口服地塞米松8mg。患者在日记中记录呕吐发作、急救治疗的使用情况以及恶心的严重程度。采用改良意向性分析方法分析疗效数据。主要终点是顺铂治疗后5天内的完全缓解（无呕吐且未使用急救治疗）。使用逻辑回归模型进行治疗组间比较，并通过报告的不良事件以及体格和实验室评估来评估耐受性。
共523例患者接受疗效评估，568例患者接受安全性评估。化疗后5天内，阿瑞匹坦组完全缓解的患者百分比为62.7%（260例患者中的163例），而标准治疗组为43.3%（263例患者中的114例；P < 0.001）。第1天，阿瑞匹坦组的完全缓解率为82.8%，标准治疗组为68.4%（P < 0.001）；第2 - 5天，阿瑞匹坦组的完全缓解率为67.7%，标准治疗组为46.8%（P < 0.001）。两个治疗组的不良事件总发生率相似（阿瑞匹坦组为72.8% [283例患者中的206例]，标准治疗组为72.6% [285例患者中的207例]），严重不良事件、因不良事件停药和死亡的发生率也相似。
在接受高剂量顺铂化疗的癌症患者中，由阿瑞匹坦（第1天125mg，第2 - 3天80mg）加昂丹司琼和地塞米松标准方案组成的治疗与单独的标准治疗相比，提供了更好的止吐保护，且总体耐受性良好。
