5HT3 and Dexamethasone in Pediatric Patients
5HT3 and Dexamethasone in Pediatric Patients
5-hydroxytryptamine (5-HT3) receptor antagonists (RAs) are a class of antiemetics used to relieve nausea and vomiting associated with chemotherapy. At this time, four 5-HT3 RAs are approved by the Food and Drug Administration (FDA) for use in the United States: ondansetron, granisetron, dolasetron, and palonosetron. Dexamethasone is a corticosteroid. These drugs have been evaluated for use in pediatric patients to treat acute emesis associated with highly or moderately emetogenic chemotherapy.
Likely to Be Effective
Jordan, K., Roila, F., Molassiotis, A., Maranzano, E., Clark-Snow, R. A., Feyer, P., & MASCC/ESMO. (2011). Antiemetics in children receiving chemotherapy. MASCC/ESMO guideline update 2009. Supportive Care in Cancer, 19(Suppl 1), 37-42.doi:10.1007/s00520-010-0994-7
Purpose & Patient Population:
To provide a consensus statement derived from published articles as well as expert opinion about antiemetic therapy in children younger than 18 years
Type of Resource/Evidence-Based Process:
This resource is a guideline, developed by the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO).
A panel of 23 oncology professionals determined the level of evidence and confidence according to EMSO and MASCC criteria. Between 2004 and June 2009, eight articles were published regarding 5-HT3 receptor antagonists (RAs) in pediatric populations (two regarding safety issues, four dose-finding or -optimizing studies, and two comparative studies), four articles reported on the NK1 RA aprepitant (one randomized study, two case reports, and one study on the liquid formulation of aprepitant), and two miscellaneous studies looked at the impact of an antiemetic pump and the value of metopimazine when added to ondansetron. Recommendations were classified using the MASCC level of scientific confidence and consensus.
Pertinent information from the published literature from 2004 to June 2009 was retrieved and reviewed for the creation of this guideline.
Database searched was Medline.
Search keywords were antiemetics, chemotherapy-induced emesis, children, neoplasms, nausea, vomiting, serotonin antagonists, neurokinin 1 receptor antagonists, phenothiazines, butyrophenones, cannabinoids, corticosteroids, and metoclopramide.
No inclusion criteria were identified.
Articles were excluded if they were review articles or addressed emesis not caused by chemotherapy.
Phase of Care and Clinical Applications:
- All patients were in active treatment.
- This guideline has application for pediatrics.
Guidelines & Recommendations:
- No designated 5-HT3 RA was recommended. (The MASCC level of confidence was moderate and level of consensus was high. The ESMO level of evidence was II and grade of recommendation was B.)
- No verifiable, high-level evidence-based consensus was possible on the dose of the individual 5-HT3 RAs.
- Corticosteroids were found to be effective antiemetics for CINV, especially when combined with a 5-HT3 RA. (The MASCC level of confidence was moderate and level of consensus was high. The ESMO level of evidence was II and grade of recommendation was B.) Safety issues when administering corticosteroids in children must strongly be considered.
- No recommendations was made regarding neurokinin 1 (NK1) RAs, but they showed promising activity. The guideline panel recommended development of more well-designed, three-agent trials testing the addition of a NK1 RA to draw firm conclusions for a recommendation.
- The guideline recommended that all pediatric patients receive antiemetic prophylaxis with a combination of a 5-HT3 RA and dexamethasone for the acute phase of highly emetogenic chemotherapy. (The MASCC level of confidence was moderate and level of consensus was high. The ESMO level of evidence was III and grade of recommendation was B.)
- For the acute phase of moderately emetogenic chemotherapy, all pediatric patients are recommended to receive antiemetic prophylaxis with a combination of a 5-HT3 RA and dexamethasone. (The MASCC level of confidence was moderate and level of consensus was high. The ESMO level of evidence was II and grade of recommendation was B.)
- For the acute phase of low and minimal emetogenic chemotherapy, not enough studies in children have been produced to make a recommendation.
Children receiving chemotherapy should receive a 5-HT3 RA and dexamethasone for antiemetic prophylaxis both in highly emetogenic and moderately emetogenic chemotherapy. A significant lack of well-designed randomized studies exist to evaluate the problem of chemotherapy-induced emesis in children. Optimal dosing in children and management of delayed and anticipatory CINV in children is not yet clear. Investigation is needed regarding the potential role of NK1 RAs and the 5-HT3 RAs palonosetron and transdermal granisetron for future consideration in pediatrics.