Osaki Akihiko, Inoue Kenichi, Sakai Hiroshi, Yamada Kazuhiko, Minato Koichi, Ohyanagi Fumiyoshi, Tokuda Yutaka, Ikeda Norihiko, Kagamu Hiroshi, Kubota Kaoru, Tamura Tomohide, Saeki Toshiaki
Department of Breast Oncology, Saitama Medical University International Medical Center, Saitama.
Division of Breast Oncology, Saitama Cancer Center, Saitama.
Jpn J Clin Oncol. 2019 Feb 1;49(2):121-129. doi: 10.1093/jjco/hyy161.
Netupitant is a novel, selective neurokinin-1 receptor antagonist used for prevention of chemotherapy-induced nausea and vomiting, a distressing side effect of chemotherapy. This double-blind, randomized, Phase II study investigated the dose-response of oral netupitant in Japanese patients receiving highly emetogenic chemotherapy.
Chemotherapy-naïve patients were randomized (1:1:1) to a single oral netupitant 30-, 100- or 300-mg dose before chemotherapy initiation. Patients received concomitant palonosetron (0.75 mg intravenously [i.v.] Day 1) and dexamethasone (9.9 mg i.v. Day 1, 8 mg orally Days 2-4).
Overall, 402 patients (30 mg: 134; 100 mg: 135; 300 mg: 133) were treated and evaluable for efficacy and safety. The primary endpoint of overall (0-120 h after chemotherapy administration) complete response (CR) rate (no emesis, no rescue medication) was 64.2%, 60.0% and 54.9% in the 30-, 100- and 300-mg arms, respectively, without statistical significance for dose-response. The safety profile of netupitant was comparable in the three arms. The plasma concentrations of netupitant and its metabolites increased with the dose increase from 30 mg to 300 mg.
No dose-response relationship of netupitant in terms of overall CR rate was observed in this study. Netupitant was well tolerated at all doses without clinically harmful safety signals observed.
JapicCTI-142 483.
奈妥吡坦是一种新型的选择性神经激肽-1受体拮抗剂，用于预防化疗引起的恶心和呕吐，这是化疗令人痛苦的副作用。这项双盲、随机、II期研究调查了口服奈妥吡坦在接受高致吐性化疗的日本患者中的剂量反应。
未接受过化疗的患者在化疗开始前被随机（1:1:1）分为口服单剂量30、100或300mg奈妥吡坦组。患者同时接受帕洛诺司琼（第1天静脉注射0.75mg）和地塞米松（第1天静脉注射9.9mg，第2 - 4天口服8mg）。
总体上，402例患者（30mg组：134例；100mg组：135例；300mg组：133例）接受治疗并可评估疗效和安全性。总体（化疗给药后0 - 120小时）完全缓解（CR）率（无呕吐、未使用解救药物）的主要终点在30mg、100mg和300mg剂量组中分别为64.2%、60.0%和54.9%，剂量反应无统计学意义。奈妥吡坦在三个剂量组中的安全性相当。奈妥吡坦及其代谢产物的血浆浓度随剂量从30mg增加到300mg而升高。
本研究未观察到奈妥吡坦在总体CR率方面的剂量反应关系。奈妥吡坦在所有剂量下耐受性良好，未观察到临床有害的安全信号。
JapicCTI - 142 483。
