Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.
Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, China.
JAMA Netw Open. 2023 Jul 3;6(7):e2326127. doi: 10.1001/jamanetworkopen.2023.26127.
Unlike substantial evidence in the prevention of chemotherapy-induced nausea and vomiting (CINV), research in the prevention of nausea and vomiting caused by concurrent chemoradiotherapy (CCRT) is currently lacking.
To compare the efficacy and safety of fosaprepitant weekly vs every 3 weeks for the prevention of nausea and emesis caused by CCRT among patients with nasopharyngeal carcinoma.
DESIGN, SETTING, AND PARTICIPANTS: This pilot randomized clinical trial was conducted at a single cancer center from November 24, 2020, to July 26, 2021, among patients with nasopharyngeal carcinoma who had achieved CINV control after 2 to 3 cycles of induction chemotherapy. Efficacy analyses were performed in the intention-to-treat population. Data were analyzed on November 4, 2022.
Eligible patients were randomly assigned (1:1) to receive fosaprepitant either weekly or every 3 weeks.
The primary end point was the proportion of patients with sustained complete response (defined as no emesis and no rescue therapy) during CCRT. Secondary end points were sustained no emesis, no nausea, no significant nausea, mean time to first emetic episode, quality of life, and 1-year progression-free survival (PFS).
A total of 100 patients (mean [SD] age, 46.6 [10.9] years; 83 [83.0%] male) who had achieved CINV control after induction chemotherapy were randomly assigned to receive fosaprepitant weekly (50 patients) or every 3 weeks (50 patients). There was no significantly significant difference in cumulative risk of emesis or rescue therapy in the group that received weekly fosaprepitant compared with those who received fosaprepitant every 3 weeks (subhazard ratio, 0.66 [95% CI, 0.43-1.02]; P = .06). The proportion of patients with sustained no emesis (38% vs 14%; P = .003) or no significant nausea (92% vs 72%; P = .002) was significantly higher in the group that received fosaprepitant weekly vs those who received fosaprepitant every 3 weeks. Treatments were well tolerated. Patients in the weekly group had improved scores for multiple quality-of-life measures. There was no significant difference in survival outcomes between groups (91.8% vs 93.7%; P = .99). In the mean brainstem dose subgroups, a possible treatment interaction effect was observed in sustained complete response (mean brainstem dose ≥36 Gy: hazard ratio [HR], 0.32 [95% CI, 0.15-0.69]; mean brainstem dose <36 Gy: HR, 0.95 [95% CI, 0.55-1.63]) and sustained no emesis (mean brainstem dose ≥36 Gy: HR, 0.21 [95% CI, 0.08-0.53]; mean brainstem dose <36 Gy: HR, 0.73 [95% CI, 0.41-1.28]).
In this pilot randomized clinical trial, there was no statistically significant difference in the complete response primary end point, but patients receiving weekly fosaprepitant were less likely to experience emesis compared with those who received fosaprepitant every 3 weeks, especially in the subgroup with a mean brainstem dose of 36 Gy or more. Weekly fosaprepitant was well tolerated and improved quality of life of patients without compromising survival.
ClinicalTrials.gov Identifier: NCT04636632.
与预防化疗引起的恶心和呕吐（CINV）的大量证据相比，目前在预防同期放化疗（CCRT）引起的恶心和呕吐方面的研究相对缺乏。
比较每周给予福沙匹坦与每 3 周给予福沙匹坦预防鼻咽癌患者 CCRT 相关恶心和呕吐的疗效和安全性。
设计、地点和参与者：这项单中心的前瞻性随机临床试验于 2020 年 11 月 24 日至 2021 年 7 月 26 日在一家癌症中心进行，入组对象为接受 2 至 3 个周期诱导化疗后控制 CINV 的鼻咽癌患者。主要分析在意向治疗人群中进行。数据于 2022 年 11 月 4 日进行分析。
符合条件的患者被随机（1:1）分为每周或每 3 周接受福沙匹坦治疗。
CCRT 期间持续完全缓解（定义为无呕吐和无解救治疗）的患者比例。次要终点为持续无呕吐、无恶心、无显著恶心、首次呕吐发作的平均时间、生活质量和 1 年无进展生存率（PFS）。
共有 100 例（平均年龄 46.6[10.9]岁；83[83.0%]为男性）患者在接受诱导化疗后控制了 CINV，被随机分为每周接受福沙匹坦（50 例）或每 3 周接受福沙匹坦（50 例）。与每 3 周接受福沙匹坦的患者相比，每周接受福沙匹坦的患者发生呕吐或解救治疗的累积风险无显著差异（亚危险比，0.66[95%CI，0.43-1.02]；P=0.06）。与每 3 周接受福沙匹坦的患者相比，每周接受福沙匹坦的患者持续无呕吐（38%比 14%；P=0.003）或无显著恶心（92%比 72%；P=0.002）的比例更高。两种治疗方案均耐受良好。每周接受福沙匹坦的患者多项生活质量评分得到改善。两组之间的生存率无显著差异（91.8%比 93.7%；P=0.99）。在平均脑干剂量亚组中，在持续完全缓解（平均脑干剂量≥36 Gy：HR，0.32[95%CI，0.15-0.69]；平均脑干剂量<36 Gy：HR，0.95[95%CI，0.55-1.63]）和持续无呕吐（平均脑干剂量≥36 Gy：HR，0.21[95%CI，0.08-0.53]；平均脑干剂量<36 Gy：HR，0.73[95%CI，0.41-1.28]）方面观察到可能的治疗相互作用效应。
在这项单中心的随机临床试验中，主要终点完全缓解的差异无统计学意义，但与每 3 周接受福沙匹坦的患者相比，每周接受福沙匹坦的患者发生呕吐的可能性较小，特别是在平均脑干剂量为 36 Gy 或更高的亚组中。每周接受福沙匹坦耐受性良好，改善了患者的生活质量，而不影响生存。
ClinicalTrials.gov 标识符：NCT04636632。
