Olanzapine combined with standard antiemetics for the prevention of nausea and vomiting in patients with germ cell tumor undergoing a 5-day cisplatin-based chemotherapy (NAVIGATE study)： A phase III crossover trial

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-04-25 DOI:10.1016/j.ejca.2025.115437

Lulu Zhang , Meiting Chen , Qingru Zhou , Cong Xue , Riqing Huang , Xiaoju Diao , Jibin Li , Jing Peng , Qiufang Zheng , Mengqian Ni , Lijia Zhou , Daining Wang , Haifeng Li , Wei Yang , Shu Dun , Zhuowei Liu , Yalan Wang , Yanxia Shi , Xin An

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引用次数: 0

Abstract

Purpose Prophylactic use of olanzapine significantly improves chemotherapy-induced nausea and vomiting (CINV) in patients receiving single-day highly emetogenic chemotherapy and 3-day cisplatin-based chemotherapy. This phase III, double-blind, placebo-controlled crossover trial aimed to evaluate the efficacy and safety of olanzapine combined with triple antiemetic therapy for CINV in germ cell tumor (GCT) patients receiving 5-day cisplatin-based chemotherapy.Methods Eligible patients receiving at least two consecutive identical courses of 5-day cisplatin-based chemotherapy were randomly assigned to either olanzapine (5 mg) or its matching placebo during days 1–7 of the first chemotherapy cycle, then crossed over to the alternate group during the second cycle. The primary endpoint was complete response (CR) rate. Main secondary endpoints included CR rates in acute and delayed phases, no nausea rates, and toxicities. Results Between January 2022 and February 2024, 77 patients were enrolled, 40 were randomized to the olanzapine group, and 37 to the placebo group during the first course. The overall CR rate was 55.8 % (43/77) in the olanzapine group, compared with 36.3 % (28/77) in the placebo group (P = 0.03). The CR rates in the acute and delayed phases were 62.3 % (48/77) vs. 40.3 % (31/77), P = 0.01, and 79.2 % (61/77) vs. 53.2 % (41/77), P = 0.04, respectively. No nausea rates were also significantly higher in the olanzapine group than those in the placebo group: 36.4 % vs. 15.6 % in overall phase (P = 0.005), 39.0 % vs.16.9 % in acute phase (P = 0.004) and 72.7 % vs. 49.4 % in delayed phase (P = 0.005). Addition of olanzapine did not increase toxicities. Conclusion This trial provides the first high-level evidence supporting the olanzapine-based four-drug combination to prevent CINV in GCT patients undergoing 5-day cisplatin-based chemotherapy. Clinical Trial Registration: ClinicalTrials.gov, number NCT05198796.

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奥氮平联合标准止吐药预防生殖细胞肿瘤患者接受5天顺铂化疗的恶心和呕吐（NAVIGATE研究）：一项III期交叉试验

目的预防使用奥氮平可显著改善接受1天高致吐性化疗和3天以顺铂为基础的化疗患者化疗诱导的恶心和呕吐（CINV）。这项III期、双盲、安慰剂对照交叉试验旨在评估奥氮平联合三联止吐治疗接受5天顺铂化疗的生殖细胞肿瘤（GCT）患者CINV的疗效和安全性。方法在第一个化疗周期的第1-7天，接受至少连续两个相同疗程的以顺铂为基础的5天化疗的符合条件的患者随机分配到奥氮平（5 mg）或其匹配的安慰剂组，然后在第二个化疗周期切换到另一组。主要终点为完全缓解（CR）率。主要次要终点包括急性期和延迟期的CR率、无恶心率和毒性。结果在2022年1月至2024年2月期间，共有77例患者入组，其中40例随机分为奥氮平组，37例随机分为安慰剂组。奥氮平组总CR率为55.8% %(43/77)，安慰剂组为36.3% % (28/77)（P = 0.03）。急性期和延迟期的CR率分别为62.3 %（48/77）比40.3 % (31/77),P = 0.01;79.2 %（61/77）比53.2 % (41/77),P = 0.04。没有恶心率也明显高于奥氮平组比安慰剂组:36.4 % 15.6 vs %在总体阶段(0.005 P = ),39.0 % vs.16.9 %在急性期(P = 0.004)和72.7 % 49.4 vs %在延迟阶段(P = 0.005)。奥氮平的加入没有增加毒性。结论该试验首次提供了高水平的证据，支持奥氮平为基础的四药联合治疗可预防5天顺铂化疗的GCT患者的CINV。临床试验注册：ClinicalTrials.gov，编号NCT05198796。

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.