奈帕（NEPA）是一种由奈妥匹坦和帕洛诺司琼组成的口服固定复方制剂，在多周期化疗中对化疗引起的恶心和呕吐（CINV）的控制效果优于口服帕洛诺司琼：一项随机、双盲、3期试验（与口服帕洛诺司琼对比）的结果 。
NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral palonosetron.
作者信息
Aapro Matti, Karthaus Meinolf, Schwartzberg Lee, Bondarenko Igor, Sarosiek Tomasz, Oprean Cristina, Cardona-Huerta Servando, Hansen Vincent, Rossi Giorgia, Rizzi Giada, Borroni Maria Elisa, Rugo Hope
机构信息
Clinique de Genolier, Institut Multidisciplinaire d'Oncologie, Case Postale (P.O. Box) 100, Route du Muids 3, 1272, Genolier, Switzerland.
Hematology and Oncology, Staedt Klinikum Neuperlach and Harlaching, Munich, Germany.
出版信息
Support Care Cancer. 2017 Apr;25(4):1127-1135. doi: 10.1007/s00520-016-3502-x. Epub 2016 Nov 24.
PURPOSE
Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study.
METHODS
This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25-120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0-120 h) CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles.
RESULTS
Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1-4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles.
CONCLUSIONS
NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.
目的
止吐指南推荐联合使用靶向预防性药物，以抑制参与呕吐的分子途径。NEPA是一种新型NK受体拮抗剂（RA）奈妥匹坦（NETU 300毫克）和帕洛诺司琼（PALO 0.50毫克）的固定口服组合，后者是一种药理学上不同的5-HT RA。在单一化疗周期中，与口服PALO相比，NEPA在预防化疗引起的恶心和呕吐（CINV）方面表现更优；本研究的目的是评估在后续周期中其疗效/安全性的维持情况。
方法
本研究是一项多国双盲研究，比较初治患者单剂量口服NEPA与口服PALO的效果，这些患者接受基于蒽环类/环磷酰胺的化疗，并在第1天同时服用12毫克（NEPA组）或20毫克（PALO组）地塞米松。主要疗效终点是第1周期延迟（25 - 120小时）完全缓解（CR：无呕吐，未使用救援药物）。在多周期扩展阶段，通过计算第2 - 4周期总体（0 - 120小时）CR患者的比例以及评估多个周期持续CR的概率来评估持续疗效。
结果
在1455例随机分组的患者中，1286例（88%）参与了多周期扩展，共计5969个周期；76%的患者完成了≥4个周期。在第1 - 4周期中，NEPA组总体CR患者的比例显著高于口服PALO组（分别为74.3%对66.6%、80.3%对66.7%、83.8%对70.3%、83.8%对74.6%；每个周期p≤0.001）。在所有4个周期中，NEPA组持续CR患者的累积百分比也更高（p < 0.0001）。在多个周期中，NEPA耐受性良好。
结论
NEPA是一种方便、符合指南的固定止吐组合，在多个化疗周期中有效且安全。
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