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TITLE: Ondansetron for the Management of Chemotherapy-Induced Nausea and
Vomiting in Pediatric Patients: A Review of the Clinical Effectiveness, Safety and
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.
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.
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?
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
Clinical practice guidelines recommended ondansetron as a treatment option for controlling
CINV in the pediatric population.
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
Ondansetron for the Management of CINV in Pediatric Patients 3
Table 1: Selection Criteria
Pediatric patients (≤18 years old) undergoing chemotherapy treatment
and are experiencing symptoms of nausea and/or vomiting –
chemotherapy-induced nausea and vomiting (CINV)
Decrease in nausea and vomiting
Guidelines and recommendations (how many tablets to administer,
when to administer, patient criteria)
Health technology assessments, systematic reviews and meta-
analyses, randomized controlled trials (RCT), non-randomized studies
and evidence-based guidelines
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
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.