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10.1093/annonc/mdu110

http://scihub22266oqcxt.onion/10.1093/annonc/mdu110
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C4071755!4071755 !24608196
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suck abstract from ncbi


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pmid24608196
      Ann+Oncol 2014 ; 25 (7 ): 1340-1346
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  • 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 #MMPMID24608196
  • Hesketh PJ ; Rossi G ; Rizzi G ; Palmas M ; Alyasova A ; Bondarenko I ; Lisyanskaya A ; Gralla RJ
  • Ann Oncol 2014[Jul]; 25 (7 ): 1340-1346 PMID24608196 show ga
  • 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.
  • |Administration, Oral [MESH]
  • |Antineoplastic Agents/*adverse effects [MESH]
  • |Dose-Response Relationship, Drug [MESH]
  • |Double-Blind Method [MESH]
  • |Drug Combinations [MESH]
  • |Female [MESH]
  • |Humans [MESH]
  • |Isoquinolines/*administration & dosage/adverse effects [MESH]
  • |Male [MESH]
  • |Middle Aged [MESH]
  • |Nausea/chemically induced/*prevention & control [MESH]
  • |Palonosetron [MESH]
  • |Pyridines/*administration & dosage/adverse effects [MESH]
  • |Quinuclidines/*administration & dosage/adverse effects [MESH]


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