Fixed Combination Antiemetic: A Literature Review on Prevention of Chemotherapy-Induced Nausea and Vomiting Using Netupitant/Palonosetron

BACKGROUND: Prevention of chemotherapy-induced nausea and vomiting (CINV) can be improved with guideline-consistent use of antiemetics. However, adherence to antiemetic guidelines remains often insufficient. Therefore, new strategies that improve adherence are needed. OBJECTIVES: To review the latest antiemetic guideline recommendations and provide an update on the use of NEPA, a fixed combination antiemetic composed of the neurokinin-1 receptor antagonist (RA) netupitant and the 5-hydroxytryptamine-3 RA palonosetron (Akynzeo®). METHODS: Analysis of the literature was performed, including guidelines, published literature, congress data on NEPA, and relevant articles on CINV. FINDINGS: Nurses are in a unique position to promote guideline-consistent antiemetic prophylaxis and are central in the education of patients and caregivers. Thus, nurses' continuous education on antiemetic treatments is key for the prevention and management of CINV. NEPA offers a simplified antiemetic therapy with the potential to increase guideline adherence.

Radiotherapy-induced nausea and vomiting (RINV): MASCC/ESMO guideline for antiemetics in radiotherapy: update 2009.

Radiation-induced nausea and vomiting (RINV) are still often underestimated by radiation oncologists. However, as many as 50-80% of patients undergoing radiotherapy (RT) will experience nausea and/or vomiting, depending on the site of irradiation. Fractionated RT may involve up to 40 fractions over a 6-8-week period, and prolonged symptoms of nausea and vomiting affect quality of life. Furthermore, uncontrolled nausea and vomiting may result in patients delaying or refusing further radiotherapy. Incidence and severity of nausea and vomiting depend on RT-related factors (irradiated site, single and total dose, fractionation, irradiated volume, radiotherapy techniques) and patient-related factors (gender, general health of the patient, age, concurrent or recent chemotherapy, psychological state, tumor stage). The new proposed guideline from the Multinational Association of Supportive Care in Cancer and European Society of Clinical Oncology summarises the updated data from the literature and takes into consideration the existing guidelines. According to the irradiated area (the most frequently studied risk factor), the proposed guideline divided these areas into four levels of emetogenic risk: high, moderate, low and minimal. In fact, the emetogenicity of radiotherapy regimens and recommendations for the appropriate use of antiemetics including 5-hydroxytryptamine receptor antagonists and steroids are given in regard to the applied radiotherapy or radiochemotherapy regimen. This updated guideline offers guidance to the treating physicians for effective antiemetic therapies in RINV.

Guidelines for the control of nausea and vomiting with chemotherapy of low or minimal emetic potential.

PURPOSE: The purpose of this study is to update the guidelines for antiemetic therapy to be used with anticancer agents of low to minimal emetic potential. METHODS: Experts from the Multinational Association of Supportive Care in Cancer (MASCC) met in Perugia in 2009 to revise the MASCC antiemetic consensus guidelines. There is an increasing number of anticancer agents which are classified as being associated with a low or minimal risk of nausea and vomiting. However, the emetic potential of such agents and particularly those given as prolonged oral therapy is not well documented, and neither is the optimal antiemetic therapy. RESULTS: The consensus is that patients receiving anticancer therapy of low emetic potential should receive single-agent antiemetic prophylaxis such as dexamethasone, 5 hydroxytryptamine3 (5HT3) receptor antagonists, or dopamine receptor antagonists. Those receiving anticancer therapy of minimal emetic potential and who have no prior history of nausea and vomiting should not receive antiemetic prophylaxis. Those who experience nausea and vomiting subsequently can receive single-agent dexamethasone, 5HT3 receptor antagonists, or dopamine receptor antagonists. CONCLUSIONS: More data are needed on the emetic potential and the outcome of antiemetic treatment with agents likely to fall into the low or minimal emetic potential category.

Antiemetics in children receiving chemotherapy. MASCC/ESMO guideline update 2009.

Only a few studies have been carried out in children on the prevention of chemotherapy-induced nausea and vomiting (CINV). 5-HT(3) receptor antagonists have been shown to be more efficacious and less toxic than metoclopramide, phenothiazines and cannabinoids. Most dose studies are available for the 5-HT(3) receptor antagonists ondansetron and granisetron. The new 5-HT(3) receptor antagonist palonosetron was evaluated in one comparative study so far showing promising activity. Combinations of a 5-HT(3) receptor antagonist and dexamethasone showed increased efficacy with respect to a 5-HT(3) receptor antagonist alone. All paediatric patients receiving chemotherapy of high or moderate emetogenic potential should receive a combination of a 5-HT(3) receptor antagonist and dexamethasone to prevent acute emesis. No studies have specifically evaluated antiemetic drugs in the prevention of chemotherapy-induced delayed and anticipatory emesis in children. The role of the NK1 receptor antagonists in children has to be further investigated, although one small study is published so far, showing promising activity in the prevention of CINV with aprepitant. The new proposed guideline from the Multinational Association of Supportive Care in Cancer and the European Society of Clinical Oncology summarises the updated data from the literature and takes into consideration the existing guidelines.

Delayed emesis: moderately emetogenic chemotherapy (single-day chemotherapy regimens only).

PURPOSE: An update of the recommendations for the prophylaxis of delayed emesis induced by moderately emetogenic chemotherapy discussed during the third Perugia Consensus Conference (June 2009) sponsored by MASCC-ESMO was presented. The review considered new studies published since the second consensus conference (April 2004). METHODS: An online search was used conducting PubMed and the search terms moderately, chemotherapy, and emesis with a restriction to papers in English. RESULTS: Overall, nine randomized controlled studies were included: four evaluating NK1 receptor antagonists, one palonosetron, and four dopamine receptor antagonists. CONCLUSIONS: In patients receiving a combination of anthracycline plus cyclophosphamide treated with a combination of aprepitant, a 5-HT(3) receptor antagonist and dexamethasone to prevent acute nausea and vomiting, aprepitant is suggested to prevent delayed emesis. In patients who do not receive aprepitant for the prophylaxis for acute emesis and in which palonosetron is recommended, a multiday oral dexamethasone is the preferred treatment for the prevention of delayed emesis. Levels of evidence and of consensus for both recommendations are moderate.

Chemotherapy-induced nausea and vomiting: contemporary approaches to optimal management. Proceedings from a symposium at the 2008 Multinational Association of Supportive Care in Cancer (MASCC) Annual Meeting.

INTRODUCTION: Chemotherapy-induced nausea and vomiting remains a significant problem for cancer patients. DISCUSSION: Patient factors such as polypharmacy, medication costs, mucositis, and depression may hinder good antiemetic control, while high workloads, poor communication, and underestimation of the problem on the part of healthcare professionals also play a role. Improving outcomes requires accurate assessment of risk factors, use of guidelines, and better adherence to antiemetic regimens. CONCLUSION: Extended-release formulations and new delivery systems such as transdermal patches, nasal sprays, and pumps provide a new strategy that may improve patient outcomes.

Evidence-based recommendations for the use of antiemetics in radiotherapy.

BACKGROUND AND PURPOSE: To report recommendations given in the Multinational Association of Supportive Care in Cancer (MASCC) International Consensus Conference regarding the use of antiemetics in radiotherapy. PATIENTS AND METHODS: A steering committee under MASCC auspice chose panel participants for the guidelines development process on prevention of chemotherapy- and radiotherapy-induced emesis (RIE). Pertinent information from published literature as of March 2004 was reviewed for the guideline process. Both the MASCC level of scientific confidence and level of consensus, and the American Society of Clinical Oncology (ASCO) type of evidence and grade for recommendation were adopted. RESULTS: Total body irradiation is classified at high risk, upper abdomen at moderate, lower thorax, pelvis, cranium (radiosurgery) and craniospinal at low, head and neck, extremities, cranium and breast at minimal risk. The recommendations for the use of antiemetics in radiotherapy are as follows: prophylaxis with a 5-HT3 antagonist in patients at high and moderate risk levels of RIE (+/-dexamethasone in the former group), prophylaxis or rescue with a 5-HT3 antagonist in the low risk group, and rescue with dopamine or a 5-HT3 receptor antagonist in minimal risk level. CONCLUSIONS: These recommendations represent a valid tool for prophylaxis and treatment of RIE in clinical practice.

Emesis induced by low or minimal emetic risk chemotherapy.

For patients treated with low or minimally emetogenic chemotherapy there is little evidence from clinical trials supporting the choice of a given antiemetic therapy or of any treatment at all. The panel recognized the necessity of considering the introduction into clinical practice of new agents in these categories, particularly oral cytotoxic agents and targeted biological agents and also the possibility of over-treatment with antiemetics. There was consensus among panel members regarding the recommended treatment for patients receiving chemotherapy agents with low and minimal emetic risk. Patients without a history of nausea and vomiting for whom minimally emetic risk chemotherapy is prescribed should not routinely receive antiemetic prophylaxis. A single agent such as a low-dose corticosteroid is suggested for patients receiving agents of low emetic risk. If nausea and vomiting occurs during subsequent cycles of chemotherapy, prophylaxis with a single agent such as a substituted benzamide, a corticosteroid, or a phenothiazine should be administered. Only patients with persistent nausea and vomiting despite treatment with these recommended agents should receive a 5-HT3 receptor antagonist in the following cycles.

Radiotherapy-induced nausea and vomiting (RINV): antiemetic guidelines.

As many as 40-80% of patients undergoing radiotherapy (RT) will experience nausea and/or vomiting, depending on the site of irradiation. Fractionated RT may involve up to 40 fractions over a 6-8 weeks period, and prolonged symptoms of nausea and vomiting could affect quality of life. Furthermore, uncontrolled nausea and vomiting may result in patients delaying or refusing further radiotherapy. Nausea and vomiting are often underestimated by radiation oncologists. Incidence and severity of nausea and vomiting depend on RT-related factors (single and total dose, fractionation, irradiated volume, radiotherapy techniques) and patient-related factors (gender, general health of the patient, age, concurrent or recent chemotherapy, psychological state, tumor stage). Current antiemetic guidelines prescribe the emetogenicity of radiotherapy regimens and recommend the use of 5-HT(3) antagonists with or without a steroid for prophylaxis in moderately and highly emetogenic treatment (MASCC, ASCO, ASHP, NCCN). The new proposed guidelines summarise the updated data from the literature and take into consideration the existing guidelines. According to the irradiated area (the most frequently studied risk factor), the proposed guidelines are divided into four levels of emetogenic risk: high, moderate, low and minimal. They offer guidance to prescribing physicians for effective antiemetic therapies in RINV.

Delayed emesis: moderately emetogenic chemotherapy.

Data on the incidence and efficacy of antiemetic prophylaxis against delayed emesis induced by moderately emetogenic chemotherapy are scanty. An overview of the literature has been done that showed the efficacy of dexamethasone in two of three randomized trials. Its optimal dose and duration of administration has not been defined. Only one of four randomized studies showed a statistically significant efficacy of 5-HT(3) antagonists. Finally, only weak evidence has been published on the efficacy of dopamine receptor antagonists.

Antiemetic guidelines: creating a more practical treatment approach.

Antiemetic guidelines from a variety of professional organizations have been available for several years. It is unclear just how often these guidelines have been used, however; data indicate that some practitioners still do not treat their patients according to the recommendations. Some of those involved in the creation of the original guidelines convened to try to create a simpler, more practical approach to the use of antiemetics in preventing chemotherapy-induced nausea and vomiting. The group's intention was to clarify available guidelines and produce a practical document, based on evidence, that could be used in everyday practice. The group created four consensus statements that would serve as a basis for their recommendations. One primary strategy used was to have chemotherapy-induced nausea and vomiting viewed as a single process that can occur throughout a treatment cycle, and not so much as an acute and a delayed process, as is usual in clinical trials. Patients' management should be considered over a 4- to 5-day period, rather than primarily dealing with the day of treatment only. The group created three tables: emetic risk of chemotherapy; treatment options based on emetic category; and antiemetic dosing recommendations. Use of these tables should make appropriate antiemetic selection more straightforward and easier for the practitioner in an everyday setting. Although this document alone may not solve all the challenges with appropriate antiemetic management, it will hopefully prove to be a step in the right direction.