Ondansetron for the Management of Chemotherapy ... Ondansetron for the Management of CINV in Pediatric

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  • Disclaimer: The Rapid Response Service is an information service for those involved in planning and providing health care in Canada. Rapid responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. Rapid responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material and may contain material in which a third party owns copyright. This report may be used for the purposes of research or private study only. It may not be copied, posted on a web site, redistributed by email or stored on an electronic system without the prior written permission of CADTH or applicable copyright owner. Links: This report may contain links to other information available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners’ own terms and conditions.

    TITLE: Ondansetron for the Management of Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients: A Review of the Clinical Effectiveness, Safety and Guidelines

    DATE: 01 February 2013 CONTEXT AND POLICY ISSUES Chemotherapy-induced nausea and vomiting (CINV) are side effects occurring in people receiving chemotherapeutic drugs for cancer treatment.1 Nausea and vomiting are two of the most frequent and distressing side effects1-3 that can significantly reduce the quality of life in patients2,4 and reduce adherence to treatment.2 CINV remains a challenge in youth as children (above the age of 5) are typically more prone to experience vomiting upon treatment.5 The incidence of CINV is dependent on numerous factors, the most important of which being the emetogenicity of the chemotherapeutic agents used.1,4 Nausea and vomiting can vary depending upon emetogenicity, and for some chemotherapeutic agents the incidence of CINV can approach 90% without prophylactic anti-emetic treatment.1 CINV can be classified into three distinct clinical phases of nausea and vomiting: anticipatory, acute, and delayed.1,2 Anticipatory phase nausea and vomiting occurs prior to receiving the first dose in a new cycle of chemotherapy and is usually in response to an adverse reaction in a previous cycle.1 Its estimated prevalence is 20-30% in pediatric patients receiving chemotherapy.1 The acute phase is defined as occurring within 24 hours of receiving treatment.1 In the delayed phase, the symptoms appear anywhere after the 24 hour period up to 120 hours and usually correspond to the use of alkylating agents or platinum compounds. The incidence of CINV with these agents is around 50%.1 Numerous classes of anti-emetic medications are available, however the current standard of practice for pediatric populations receiving moderate to highly emetogenic chemotherapy includes treatment with a 5-hydroxytryptamine3 (5-HT3) antagonist and corticosteroids.

    3,5,6 Since the 5-HT3 receptors found in the chemoreceptor trigger zone of the brain are involved in the emetic reflex, the 5-HT3 antagonists are quite valuable in controlling emesis,

    2,7 even though 30% of patients are non-responders.7 Ondansetron, granisetron, dolasetron, tropisetron, and palonosetron are medications belonging to the 5-HT3 antagonist class.

    7 The main side effects of 5-HT3 antagonists include headache, diarrhea, constipation, sedation/somnolence, abdominal

  • Ondansetron for the Management of CINV in Pediatric Patients 2

    pain, and dizziness.1,4,8 The administration of 5-HT3 antagonists has been associated with changes in electrocardiogram (ECG) readings and may be of concern in some instances.9 The purpose of this report is to provide evidence on the clinical effectiveness, safety, and harms of ondansetron for the management of CINV in pediatric populations. It will also report on evidence-based guidelines for the use of ondansteron for CINV in pediatric populations. RESEARCH QUESTIONS 1. What is the clinical effectiveness of ondansetron for the management of chemotherapy-

    induced nausea and vomiting (CINV) in pediatric patients? 2. What is the clinical evidence on the safety and harms of ondansetron for the management

    of CINV in pediatric patients? 3. What are the evidence-based guidelines regarding the use of ondansetron for the

    management of CINV in pediatric patients? KEY FINDINGS For the management of CINV in the pediatric population, the antiemetic effects of ondansetron plus dexamethasone appeared to be better than ondansetron alone or placebo. There was no statistically significant difference in antiemetic effect between ondansetron and tropisetron. There were some inconsistencies in the results for antiemetic effects of ondansetron compared with granisetron. Numerical values suggested that the antiemetic effects of palonosetron was greater compared to ondansetron, however it was unclear if the differences were statistically significant. It should be noted that in most instances, for each comparison there was only one relevant study. Clinical practice guidelines recommended ondansetron as a treatment option for controlling CINV in the pediatric population. METHODS Literature Search Strategy A limited literature search was conducted on key resources including PubMed, The Cochrane Library (2012, Issue 12), University of York Centre for Reviews and Dissemination (CRD) databases, EMBASE, Canadian and major international health technology agencies, as well as a focused Internet search. No filters were applied to limit the retrieval by study type. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2008 and January 3, 2013. Selection Criteria and Methods One reviewer screened the titles and abstracts of the retrieved publications and selected potentially relevant articles for retrieval of full-text publications for further investigation. A second reviewer evaluated the full-text publications for final selection, according to the criteria listed in Table 1.

  • Ondansetron for the Management of CINV in Pediatric Patients 3

    Table 1: Selection Criteria

    Population

    Pediatric patients (≤18 years old) undergoing chemotherapy treatment and are experiencing symptoms of nausea and/or vomiting – chemotherapy-induced nausea and vomiting (CINV)

    Intervention

    Ondansetron

    Comparator

    Placebo

    Active comparators

    Outcomes

    Decrease in nausea and vomiting

    Adverse events

    Guidelines and recommendations (how many tablets to administer, when to administer, patient criteria)

    Study Designs

    Health technology assessments, systematic reviews and meta- analyses, randomized controlled trials (RCT), non-randomized studies and evidence-based guidelines

    Exclusion Criteria Studies were excluded if they did not satisfy the selection criteria in Table 1, if they were published prior to 2008, or duplicate publications of the same study and did not provide additional relevant information. Individual studies which were included in at least one of the included systematic reviews were excluded. Systematic reviews which did not report results specifically for ondansetron were excluded. Critical Appraisal of Individual Studies

    Critical appraisal of a study was conducted based on an assessment tool appropriate for the particular study design. The AMSTAR checklist10 was used for systematic reviews; the Downs and Black checklist11 for RCTs and non-randomized studies; and the AGREE checklist12 for guidelines. For the critical appraisal, a numeric score was not calculated. Instead, the strength and limitations of the study were described. SUMMARY OF EVIDENCE Quantity of Research Available The literature search yielded 226 citations. Upon screening titles and abstracts, 213 articles were excluded and 13 potentially relevant articles were selected for full-text review. Five potentially relevant articles were identified from the grey literature. Of these 18 articles, 12 did not satisfy the inclusion criteria and were excluded. Two systematic reviews, one RCT, one non- randomized study, and two evidence-based guidelines were relevant and selected for inclusion. No relevant health technology assessment was identified. Details of the study selection process are outlined in Appendix 1.

  • Ondansetron for the Management of CINV in Pediatric Patients 4

    Summary of Study Characteristics Characteristics of the included systematic reviews, RCTs, non-randomized studies and guidelines are summarized below and details are provided in Appendices 2 and 3. Systematic reviews

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