Rebecca A. Clark-Snow

Recommendations for the Use of Antiemetics: Evidence-Based, Clinical Practice Guidelines

THE GOAL OF ANTIEMETIC therapy is to prevent nausea and vomiting completely. This goal is achieved for many patients receiving chemotherapy or radiation therapy, and is based on clinical and basic research that has steadily improved the control of emesis over the last 20 years. As therapy has become more effective, it has also become safer, with few side effects associated with the most commonly used regimens. These regimens are convenient for patients to receive and for health care professionals to administer. However, despite improvements, a significant number of patients still experience emesis, and efforts to reduce this side effect of treatment must continue. As antiemetic usage has grown, the classes of agents available for antiemetic treatment, the number of agents, and the indications for antiemetics have all increased as well. The prevention of delayed emesis and anticipatory emesis is equal in importance to the need to prevent acute chemotherapyand radiation-induced emesis. Additionally, managing special and difficult emetic problems and selecting the proper antiemetic approach necessitate identification of the patient’s emetic risk. Although the neuropharmacologic basis of emesis is still incompletely understood, the selection of an appropriate antiemetic regimen is possible and can have an impact on several aspects of clinical care. Goals related to the complete control of emesis, ie, no vomiting, include providing care that is convenient for the patient, treatment that reduces hospitalization and time in the ambulatory setting, and therapy that enhances the patient’s quality of life. Additionally, practitioners need to be mindful of reducing costs of treatment while achieving these goals. 1-3

Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update

PURPOSE To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology. METHODS A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library, and meeting materials from ASCO and the Multinational Association for Supportive Care in Cancer were all searched. Primary outcomes of interest were complete response and rates of any vomiting or nausea. RESULTS Thirty-seven trials met prespecified inclusion and exclusion criteria for this systematic review. Two systematic reviews from the Cochrane Collaboration were identified; one surveyed the pediatric literature. The other compared the relative efficacy of the 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonists. RECOMMENDATIONS Combined anthracycline and cyclophosphamide regimens were reclassified as highly emetic. Patients who receive this combination or any highly emetic agents should receive a 5-HT(3) receptor antagonist, dexamethasone, and a neurokinin 1 (NK(1)) receptor antagonist. A large trial validated the equivalency of fosaprepitant, a single-day intravenous formulation, with aprepitant; either therapy is appropriate. Preferential use of palonosetron is recommended for moderate emetic risk regimens, combined with dexamethasone. For low-risk agents, patients can be offered dexamethasone before the first dose of chemotherapy. Patients undergoing high emetic risk radiation therapy should receive a 5-HT(3) receptor antagonist before each fraction and for 24 hours after treatment and may receive a 5-day course of dexamethasone during fractions 1 to 5. The Update Committee noted the importance of continued symptom monitoring throughout therapy. Clinicians underestimate the incidence of nausea, which is not as well controlled as emesis.

Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference

Despite the relevant progress achieved in the last 20 years,vomiting and, especially, nausea, continue to be two of themost distressing side-effects of cancer chemotherapy. In the late1990s several professional organizations publishedrecommendations on the optimal antiemetic prophylaxis inpatients submitted to chemotherapy and radiotherapy.Subsequently, due to the emergence of new findings and newantiemetic agents since the first recommendations from 1997,representatives from several oncology societies met in Perugia,Italy, in 2004 and updated the antiemetic guidelines. On 20–21June 2009 the European Society of Medical Oncology (ESMO)and the Multinational Association of Supportive Care inCancer (MASCC) organized the third Consensus Conferenceon antiemetics in Perugia. The results of this Conference arereported in this paper.The methodology for the guideline process was based ona literature review through 1 June 2009 using MEDLINE(National Library of Medicine, Bethesda, MD, USA) and otherdatabases, with evaluation of the evidence by an expert panelcomposed of 23 oncology professionals in clinical medicine,medical oncology, radiation oncology, surgical oncology,oncology nursing, statistics, pharmacy, pharmacology, medicalpolicy and decision making. With the participating expertscoming from 10 different countries, on five continents, webelieve that this is the most representative and evidence-basedguideline process that has yet been performed.The panel comprised 10 committees dealing with majortopics in this field (e.g. acute or delayed nausea and vomitinginduced by highly emetogenic chemotherapy). Althoughprevention of acute and delayed nausea and vomiting inducedby highly and moderately emetogenic chemotherapy (HEC andMEC) had specific committees, these worked finally together, as

Antiemetics: American Society of Clinical Oncology Focused Guideline Update

PURPOSE To update a key recommendation of the American Society of Clinical Oncology antiemetic guideline. This update addresses the use of the oral combination of netupitant (a neurokinin 1 [NK1] receptor antagonist) and palonosetron (a 5-hydroxytryptamine-3 [5-HT3] receptor antagonist) for the prevention of acute and delayed nausea and vomiting in patients receiving chemotherapy. METHODS An update committee conducted a targeted systematic literature review and identified two phase III clinical trials and a randomized phase II dose-ranging study. RESULTS In one phase III trial, the oral combination of netupitant and palonosetron was associated with higher complete response rates (no emesis and no rescue medications) compared with palonosetron alone in patients treated with anthracycline plus cyclophosphamide chemotherapy (74% v 67% overall; P = .001). In another phase III trial, the oral combination of netupitant and palonosetron was safe and effective across multiple cycles of moderately or highly emetogenic chemotherapies. In the phase II dose-ranging study, each dose of netupitant (coadministered with palonosetron 0.50 mg) produced higher complete response rates than palonosetron alone among patients receiving cisplatin-based chemotherapy. The highest dose of netupitant (ie, 300 mg) was most effective. RECOMMENDATIONS All patients who receive highly emetogenic chemotherapy regimens (including anthracycline plus cyclophosphamide) should be offered a three-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone. The oral combination of netupitant and palonosetron plus dexamethasone is an additional treatment option in this setting. The remaining recommendations from the 2011 ASCO guideline are unchanged pending a full update. Additional information is available at www.asco.org/guidelines/antiemetics and www.asco.org/guidelineswiki.

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.

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-HT3 antagonists. Finally, only weak evidence has been published on the efficacy of dopamine receptor antagonists.

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-HT3 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.

Antiemetics in children receiving chemotherapy

Only a few studies have been carried out in children on the prevention of chemotherapy-induced acute emesis. 5-HT3 antagonists have been shown to be more efficacious and less toxic than metoclopramide, phenothiazines and cannabinoids. The optimal dose and scheduling of the 5-HT3 antagonists has not been identified. Combinations of a 5-HT3 antagonist and dexamethasone show increased efficacy with respect to 5-HT3 antagonists alone. All pediatric patients receiving chemotherapy of high or moderate emetogenic potential should receive a combination of a 5-HT3 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.

Role of the nurse in patient education and follow-up of people receiving oral chemotherapy treatment: an International survey

PurposeThe aim of this study was to explore the nursing role in education and follow-up of patients who were taking oral chemotherapy (CT) and to identify the worldwide gap in patient education about oral CT.Materials and methodsMultinational Association of Supportive Care in Cancer members were invited to participate in a survey on oral CT. Nurse coordinators collected data via a 16-item questionnaire. Respondents totaled 1115 oncology nurses from 15 countries.ResultsFindings showed that about half of subjects work in outpatient/ambulatory clinics and had given at least two or more oral CT drugs. Although 52% had some type of guidelines/protocols, 47% reported not having received any education about oral CT drugs. While 64% report being involved in patient education, 58% of subjects indicated lack of patient education materials that are specific for oral CT agents. Only 27% stated that they gave all necessary information such as when and how to take the drugs, drug safety and storage, side effects, and symptom management. Reasons for not being involved in oral CT education and follow-up included beliefs that the physician plans the oral CT and gives patients necessary instructions (34%), that nurses only see patients who receive intravenous chemotherapy (16%), that nurses have lack of knowledge about oral agents (15%), and belief that physicians are responsible for patient follow-up. The nurses suggested better education and follow-up of patients to include the written patient education materials (33%) and professional education for nurses (30%).ConclusionsFindings revealed the need for professional education for nurses to ensure comprehensive, consistent patient education and development of written materials for patients receiving oral CT treatment.

Chemotherapy-induced nausea and vomiting: contemporary approaches to optimal management

IntroductionChemotherapy-induced nausea and vomiting remains a significant problem for cancer patients.DiscussionPatient 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.ConclusionExtended-release formulations and new delivery systems such as transdermal patches, nasal sprays, and pumps provide a new strategy that may improve patient outcomes.