Neurokinin-1-Receptor Antagonists: A New Approach in Antiemetic Therapy

Abstract

Aprepitant (Emend®), the first neurokinin-1-receptor antagonist (NK-1-RA), represents a new class of antiemetics. Aprepitant has been approved for the prevention and treatment of acute (0-24 h after chemotherapy) and delayed (1-5 days after chemotherapy) emesis resulting from cisplatin-based chemotherapy and moderately emetogenic chemotherapy. The addition of aprepitant to standard antiemetic therapy in cisplatin-based chemotherapy significantly improves emesis protection in general and, in particular, in the delayed phase by approximately 20%. Results from a recently published study in patients receiving moderately emetogenic chemotherapy suggest a benefit of aprepitant when combined with dexamethasone and a 5-HT3 receptor antagonist for the prevention of acute emesis, followed by aprepitant as a single agent in the prevention of delayed emesis. Altogether, the addition of aprepitant to the standard antiemetic regimen (5-HT3 receptor antagonist and dexamethasone) significantly improves the protection against vomiting in the acute as well as in the delayed phase in highly and moderately emetogenic chemotherapies. Therefore, the combination of a 5-HT3 receptor antagonist, dexamethasone and aprepitant should be considered as a new standard antiemetic therapy.

Chemotherapy-induced pica and anorexia are reduced by common hepatic branch vagotomy in the rat

“…Antiemetic treatments may differ depending on efficacy for the acute (up to 1 day after treatment) and delayed (1-5 days after treatment) phases of emesis associated with cisplatin and other chemotherapy treatments (50). 5-HT 3 receptor antagonists largely control the severity of acute-phase emesis, while the NK 1 receptor antagonists appear most useful for treatment of delayed chemotherapy-induced vomiting (28). The present data show increased pica in intact rats most markedly within the first and second days after injection, as well as a reappearance of significant kaolin intake on the fourth day after cisplatin treatment, but also on days 6 -10 ( Figs.…”

Aprepitant as Salvage Therapy in Patients with Chemotherapy-Induced Nausea and Emesis Refractory to Prophylaxis with 5-HT₃ Antagonists and Dexamethasone

“…Aprepitant has also shown to improve antiemetic control in patients with breast cancer receiving moderately emetogenic anthracyclinebased chemotherapy [17]. Aprepitant is considered as a new standard in antiemetic primary prophylaxis in combination with 5-HT3 antagonists und dexamethasone in patients receiving cisplatin-based or moderate emetogentic prohylaxis [18]. The aim of the current phase II trial was to evaluate the antiemetic efficacy of adding aprepitant to the antiemetic regimen in patients with chemotherapy-induced nausea and emesis refractory to standard prophylaxis with dexamethasone and 5-HT3 antagonists.…”

Chemotherapie-induziertes Erbrechen - Praktische Anleitung zur Prophylaxe und Therapie

“…4) [10,15]. Studien zufolge kann durch die zusätzli-che Gabe von Aprepitant das Auftreten von akutem und besonders verzögertem Erbrechen bei hoch emetogenen Chemotherapien in bis zu 20% der Fälle gesenkt werden [8].…”

“…Da Aprepitant ein moderater CYP 3A4-Inhibitor ist, sollte bei Komedikation mit Dexamethason die Desamethasondosis halbiert werden. Bedeutsame Interaktionen mit Chemotherapeutika sind nicht beschrieben [10].…”

“…Imipenem), suboptimale Dosierung, Hirnmetastasen oder gastrointestinale Obstruktionen, bedacht bzw. abgeklärt werden[10].ASCO-Guidelines: www.asco.org MASCC-Guidelines: www.mascc.org NCCN-Guidelines: www.nccn.org Autorisierte Übersetzung der MASCC Guidelines durch die ASO: www.onkosupport.de Autorenerklärung: WV erklärt, dass keine finanziellen Verbindungen mit einer Firma bestehen, deren Produkt in dem Artikel eine wichtige Rolle spielt (oder mit einer Firma, die ein Konkurrenzprodukt vertreibt). KJ und H-JS haben Vorträge für die Firmen MSD (Aprepitant) und Hofmann-LaRoche (Granisetron) gehalten.…”