Your browser doesn't support javascript.
loading
Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose-ranging pivotal study.
Hesketh, P J; Rossi, G; Rizzi, G; Palmas, M; Alyasova, A; Bondarenko, I; Lisyanskaya, A; Gralla, R J.
Afiliação
  • Hesketh PJ; Lahey Hospital & Medical Center, Burlington, USA. Electronic address: paul.hesketh@lahey.org.
  • Rossi G; Corporate Clinical Development and Statistics & Data Management, Helsinn Healthcare SA, Lugano, Switzerland.
  • Rizzi G; Corporate Clinical Development and Statistics & Data Management, Helsinn Healthcare SA, Lugano, Switzerland.
  • Palmas M; Corporate Clinical Development and Statistics & Data Management, Helsinn Healthcare SA, Lugano, Switzerland.
  • Alyasova A; Federal State Institution, Privolzhsky District Medical Center under the Federal Medical-Biological Agency of Russia, Nizhny Novgorod, Russia.
  • Bondarenko I; Dnepropetrovsk Medical Academy, Dnepropetrovsk, Ukraine.
  • Lisyanskaya A; City Clinical Oncology Dispensary, Saint Petersburg, Russia.
  • Gralla RJ; Albert Einstein College of Medicine, Bronx, USA.
Ann Oncol ; 25(7): 1340-1346, 2014 Jul.
Article em En | MEDLINE | ID: mdl-24608196
BACKGROUND: NEPA is a novel oral fixed-dose combination of netupitant (NETU), a new highly selective neurokinin-1 (NK1) receptor antagonist (RA) and palonosetron (PALO), a pharmacologically and clinically distinct 5-hydroxytryptamine type 3 (5-HT3) RA. This study was designed to determine the appropriate clinical dose of NETU to combine with PALO for evaluation in the phase 3 NEPA program. PATIENTS AND METHODS: This randomized, double-blind, parallel group study in 694 chemotherapy naïve patients undergoing cisplatin-based chemotherapy for solid tumors compared three different oral doses of NETU (100, 200, and 300 mg) + PALO 0.50 mg with oral PALO 0.50 mg, all given on day 1. A standard 3-day aprepitant (APR) + IV ondansetron (OND) 32 mg regimen was included as an exploratory arm. All patients received oral dexamethasone on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) during the overall (0-120 h) phase. RESULTS: All NEPA doses showed superior overall CR rates compared with PALO (87.4%, 87.6%, and 89.6% for NEPA100, NEPA200, and NEPA300, respectively versus 76.5% PALO; P < 0.050) with the highest NEPA300 dose studied showing an incremental benefit over lower NEPA doses for all efficacy endpoints. NEPA300 was significantly more effective than PALO and numerically better than APR + OND for all secondary efficacy endpoints of no emesis, no significant nausea, and complete protection (CR plus no significant nausea) rates during the acute (0-24 h), delayed (25-120 h), and overall phases. Adverse events were comparable across groups with no dose response. The percent of patients developing electrocardiogram changes was also comparable. CONCLUSIONS: Each NEPA dose provided superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with PALO following highly emetogenic chemotherapy; however, NEPA300 was the best dose studied, with an advantage over lower doses for all efficacy endpoints. The combination of NETU and PALO was well tolerated with a similar safety profile to PALO and APR + OND.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piridinas / Quinuclidinas / Vômito / Isoquinolinas / Náusea / Antineoplásicos Tipo de estudo: Clinical_trials Limite: Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piridinas / Quinuclidinas / Vômito / Isoquinolinas / Náusea / Antineoplásicos Tipo de estudo: Clinical_trials Limite: Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2014 Tipo de documento: Article