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Published online: 27 November 2015
^ Springer International Publishing Switzerland 2015
Abstract An oral fixed combination of netupitant/palonosetron (NEPA; Akynzeo®) is available for use in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Netupitant is a highly selective neurokinin-1 receptor antagonist and palonosetron is a serotonin 5-HT^sub 3^ receptor antagonist with a distinct pharmacological profile. Complete response rates during the delayed, acute and overall phases were significantly higher with single-dose netupitant 300 mg plus palonosetron 0.5 mg than with single-dose palonosetron 0.5 mg in cycle 1 of cisplatin-based highly emetogenic chemotherapy (HEC) in a phase II trial and with single-dose netupitant/palonosetron 300/0.5 mg than with single-dose palonosetron 0.5 mg in cycle 1 of anthracycline-cyclophosphamide (AC) moderately emetogenic chemotherapy (MEC) in a phase III trial; the greater efficacy of netupitant/palonosetron was maintained over repeated cycles of AC MEC in the phase III trial. In another phase III trial, netupitant/palonosetron 300/0.5 mg was effective over repeated cycles of non-AC MEC or HEC. Netupitant/palonosetron was well tolerated, with no cardiac safety concerns. The convenience of administering netupitant/palonosetron as a single dose in a fixed combination has the potential to improve adherence to CINV prevention guidelines. In conclusion, netupitant/palonosetron is an important option to consider in the prevention of acute and delayed CINV in patients receiving MEC or HEC.
1 Introduction
Nausea and vomiting are important adverse effects of chemotherapy that may affect adherence to treatment, as well as adversely impacting health-related quality of life [1, 2]. The neurotransmitters serotonin (the endogenous ligand of the serotonin 5-HT3 receptor) and substance P [the preferred endogenous ligand of the neurokinin-1 (NK1) receptor] play a major role in the regulation of chemotherapy-induced nausea and vomiting (CINV) [3, 4]. Historically, serotonin has been implicated in acute emesis and substance P has been considered the dominant mediator of delayed emesis, although given the complexity of emetic pathways it is likely that multiple overlapping neurotransmitters play a role in both acute and delayed CINV [3-5].
Combination antiemetic therapy is the standard of care for the prevention of CINV in patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) [6-8]. Guidelines generally recommend a 5-HT3 receptor antagonist (RA) plus an NK1 RA and a corticosteroid for use in HEC, and...