Efficacy of neurokinin-1 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based chemotherapy: A systematic review and meta-analysis
Introduction
Nausea and vomiting are common adverse events in cancer patients receiving chemotherapy (Laszlo, 1983; Navari and Aapro, 2016). Chemotherapy-induced nausea and vomiting (CINV) can significantly affect health-related quality of life (QoL) of cancer patients and can impair compliance with treatments (Ballatori and Roila, 2003; Ballatori et al., 2007). For these reasons, a correct management of CINV is essential. According to guidelines, all antineoplastic agents are classified, based on their emetogenic potential, on a 4-group scale: high (emetic risk >90%), moderate (30%–90%), low (10%–30%), and minimal (<10%) emetogenic chemotherapy (Ballatori et al., 2007). For each category, guidelines recommend different strategies to prevent CINV: a triple drug strategy with 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists (RAs) plus dexamethasone plus Neurokinin-1 (NK-1) RAs is currently recommended in highly emetogenic chemotherapy (HEC) (such as cisplatin-based treatment or combination of anthracyclines and cyclophosphamide in breast cancer patients) to prevent acute and delayed nausea and vomiting (Roila et al., 2016; Moher et al., 2009). In patients receiving moderately emetogenic chemotherapy (MEC) such as oxaliplatin and irinotecan, only 5-HT3RA and dexamethasone are recommended. Instead, for carboplatin, the latest ESMO-MASCC guidelines recommend a different prophylaxis compared to other MEC, consisting in a triple combination of 5-HT3RA plus dexamethasone plus NK-1RA (Roila et al., 2016). However, the level of confidence was moderate, and the consensus reached among panelists was not unanimous.
To better define the value of NK-1RAs addition in the prevention of emesis for patients receiving carboplatin-based chemotherapy, we conducted a systematic review and a literature-based meta-analysis of all randomized trials (RCTs) published to date.
Section snippets
Methods
This systematic review and meta-analysis was conducted and reported according to PRISMA guidelines (Herrstedt et al., 2011). Full protocol of the review is available on request from the corresponding author.
The systematic review was performed in January 2017 and updated in June 2017, in order to identify all RCTs comparing NK1RA + dexamethasone + 5-HT3RA vs. dexamethasone + 5-HT3RA in patients receiving the first cycle of carboplatin-based chemotherapy. PubMed search was based on the following
Results
Out of 180 records, 173 were excluded and 7 trials were identified as potentially eligible (Fig. 1) (Tanioka et al., 2013; Ito et al., 2014; Kusagaya et al., 2015; Kaushal et al., 2015; Maehara et al., 2015; Yahata et al., 2016; Hesketh et al., 2016). In addition, 2 trials were found in the proceedings of meetings (Weinstein et al., 2016; Gralla et al., 2010), for a total of 9 trials potentially eligible. More specifically, 7 trials tested the role of aprepitant, 1 fosaprepitant and 1
Discussion
In this meta-analysis, we collected the results of all RCTs comparing antiemetic prophylaxis based on the combination of 5-HT3RA plus dexamethasone with the same combination implemented with a NK1RA, in patients undergoing carboplatin-based chemotherapy. Through the comparison of complete response rates (defined as no episodes of emesis and no need for rescue medications), we demonstrated that the addition of a NK1RA significantly increases the rate of success in the control of CINV after the
Funding
None.
Conflicts of interest statement
Massimo Di Maio had roles as advisor, and speaker’s fee for Merck Sharp & Dohme, AstraZeneca, Bayer, Janssen, Bristol Myers Squibb, and Eli Lilly. Emilio Bria had roles as advisor, and speakers’ fee for Merck Sharp & Dohme, AstraZeneca, Celgene, Pfizer, Eli-Lilly, Bristol Myers Squibb, and Novartis. All remaining authors declared no conflicts of interest.
References (24)
- et al.
Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy
Lung Cancer
(2014) - et al.
Evaluation of palonosetron and dexamethasone with or without aprepitant to prevent carboplatin-induced nausea and vomiting in patients with advanced non-small-cell lung cancer
Lung Cancer
(2015) - et al.
2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea of nausea and vomiting in advanced cancer patients
Ann. Oncol.
(2016) - et al.
Impact of nausea and vomiting on quality of life in cancer patients during chemotherapy
Health Qual. Life Outcomes
(2003) - et al.
The impact of chemotherapy-induced nausea and vomiting on health-related quality of life
Support. Care Cancer
(2007) - et al.
Prevention of chemotherapy-induced nausea and vomiting and the role of neurokinin 1 inhibitors: from guidelines to clinical practice in solid tumors
Anticancer Drugs
(2013) - et al.
Assessing the magnitude of antiemetic benefit with the addition of the NK1 receptor antagonist aprepitant for all platinum agents: analysis of 1872 patients in prospective randomized clinical phase III trials
J. Clin. Oncol.
(2010) - et al.
Acute emesis: moderately emetogenic chemotherapy
Support. Care Cancer
(2011) - et al.
Efficacy of the neurokinin-1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin-based chemotherapy
Cancer
(2016) - et al.
Antiemetics: American Society of Clinical Oncology clinical practice guideline update
J. Clin. Oncol.
(2017)
Efficacy benefit of a NK1 receptor antagonist (NK1RA) in patients receiving carboplatin: supportive evidence with NEPA (a fixed combination of the NK1 RA, netupitant, and palonosetron) and aprepitant regimens
Support. Care Cancer
Is the addition of a neurokinin-1 receptor antagonist beneficial in moderately emetogenic chemotherapy?-A systematic review and meta-analysis
Support. Care Cancer
Cited by (15)
Simulation of the oxidative metabolization pattern of netupitant, an NK<inf>1</inf> receptor antagonist, by electrochemistry coupled to mass spectrometry
2021, Journal of Pharmaceutical AnalysisCitation Excerpt :The quality of life of patients has been a major area of concern over the last decades, with efforts made to improve the palliative care of individuals with terminal illnesses or to relieve the side effects associated with chemotherapy protocols. Netupitant, a relatively new and selective neurokinin-1 (NK1) receptor antagonist, is used either in monotherapy or in combination with palonosetron (a 5-HT3 receptor antagonist) for the control of unwanted side effects (e.g., nausea and emesis) associated with the postoperative condition or those caused by acute and delayed chemotherapy [1–4]. Given the wide distribution of the NK1 receptors throughout the central and peripheral nervous systems and the omnipresence of the substance P (SP) peptide in all bodily fluids, a better understanding of the SP/NK1 receptor system is warranted to add to our understanding of how these molecules contribute to the molecular bases of numerous human pathologies, as suggested by Huang and Korlipara [5] and Muñoz and Coveñas [6].
Duration of dexamethasone administration for the prevention of chemotherapy-induced nausea and vomiting – A systematic review and meta-analysis
2020, Critical Reviews in Oncology/HematologyCitation Excerpt :However, several advances in pharmacotherapy have improved control of delayed emesis. In particular, multiple randomised controlled trials and a recent meta-analysis have shown NK-1 receptor antagonists significantly improve control of acute and delayed CINV in both highly and moderately emetogenic chemotherapy (Di Maio et al., 2018; dos Santos et al., 2012). Furthermore, extended half-life 5-HT3 receptor antagonists such as palonosetron and ramosetron have further improved control of CINV over first-generation agents with a shorter half-life, such as ondansetron or dolasetron (Aapro et al., 2005; Kang et al., 2020; Likun et al., 2011).
Cisplatin-Induced Anorexia and Pica Behavior in Rats Enhanced by Chronic Stress Pretreatment
2022, Frontiers in Pharmacology