Aapro M, Rugo H, Rossi G, Rizzi G, Borroni M E, Bondarenko I, Sarosiek T, Oprean C, Cardona-Huerta S, Lorusso V, Karthaus M, Schwartzberg L, Grunberg S
Institut Multidisciplinaire d'Oncologie, Clinique de Genolier, Genolier, Switzerland.
Comprehensive Cancer Center, University of California San Francisco, San Francisco, USA.
Ann Oncol. 2014 Jul;25(7):1328-1333. doi: 10.1093/annonc/mdu101. Epub 2014 Mar 5.
Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 RA, which targets dual antiemetic pathways.
This multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-naïve patients receiving moderately emetogenic (anthracycline-cyclophosphamide) chemotherapy evaluated the efficacy and safety of a single oral dose of NEPA versus a single oral dose (0.50 mg) of PALO. All patients also received oral dexamethasone (DEX) on day 1 only (12 mg in the NEPA arm and 20 mg in the PALO arm). The primary efficacy end point was complete response (CR: no emesis, no rescue medication) during the delayed (25-120 h) phase in cycle 1.
The percentage of patients with CR during the delayed phase was significantly higher in the NEPA group compared with the PALO group (76.9% versus 69.5%; P = 0.001), as were the percentages in the overall (0-120 h) (74.3% versus 66.6%; P = 0.001) and acute (0-24 h) (88.4% versus 85.0%; P = 0.047) phases. NEPA was also superior to PALO during the delayed and overall phases for all secondary efficacy end points of no emesis, no significant nausea and complete protection (CR plus no significant nausea). NEPA was well tolerated with a similar safety profile as PALO.
NEPA plus a single dose of DEX was superior to PALO plus DEX in preventing CINV following moderately emetogenic chemotherapy in acute, delayed and overall phases of observation. As a fixed-dose antiemetic drug combination, NEPA along with a single dose of DEX on day 1 offers guideline-based prophylaxis with a convenient, single-day treatment.
止吐指南推荐联合使用针对呕吐相关多种分子途径的药物，以最大程度预防和控制化疗引起的恶心和呕吐（CINV）。NEPA是一种新型口服固定剂量复方制剂，由300mg奈妥匹坦（一种高选择性NK1受体拮抗剂（RA））和0.50mg帕洛诺司琼（PALO，一种药理和临床特性独特的5-HT3 RA）组成，作用于双重止吐途径。
这项在1455例初治化疗患者中开展的多中心、随机、双盲、平行组III期研究（NCT01339260），纳入接受中度致吐性（蒽环类药物-环磷酰胺）化疗的患者，评估单次口服NEPA与单次口服（0.50mg）PALO的疗效和安全性。所有患者仅在第1天接受口服地塞米松（DEX）（NEPA组12mg，PALO组20mg）。主要疗效终点为第1周期延迟期（25 - 120小时）的完全缓解（CR：无呕吐、未使用解救药物）。
NEPA组延迟期CR患者的百分比显著高于PALO组（76.9%对69.5%；P = 0.001），总体期（0 - 120小时）（）74.3%对66.6%；P = 0.001）和急性期（0 - 24小时）（88.4%对）85.0%；P = 0.047）也是如此。在无呕吐、无明显恶心和完全保护（CR加无明显恶心）的所有次要疗效终点方面，NEPA在延迟期和总体期也优于PALO。NEPA耐受性良好，安全性与PALO相似。
在中度致吐性化疗后的CINV预防中，在观察的急性期、延迟期和总体期，NEPA加单次剂量DEX优于PALO加DEX。作为一种固定剂量的止吐药物复方制剂，NEPA与第1天单次剂量DEX一起提供了基于指南的预防措施，且治疗方便，只需一天。
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