Antiemetic medication for prevention and treatment of chemotherapy induced nausea and vomiting in childhood

BACKGROUND: Nausea and vomiting are still a problem for children undergoing treatment for malignancies despite new antiemetic therapies. Optimising antiemetic regimens could improve quality of life by reducing nausea, vomiting and associated clinical problems. OBJECTIVES: To assess the effectiveness and adverse events of pharmacological interventions in controlling anticipatory, acute and delayed nausea and vomiting in children and young people (aged < 18 years) about to receive/receiving chemotherapy. SEARCH STRATEGY: Searches included CENTRAL, MEDLINE, EMBASE and LILACS, trial registries from their earliest records to February 2008, and ASCO, MASCC and SIOP conference proceedings from 2001 to 2007. We examined references of systematic reviews and contacted trialists for information on further studies. SELECTION CRITERIA: Two authors independently screened abstracts to identify randomised controlled trials (RCTs) that compared a pharmacological antiemetic, cannabinoid or benzodiazepine with placebo or any alternative active intervention in children and young people (< 18 years) with a diagnosis of cancer who were to receive chemotherapy. DATA COLLECTION AND ANALYSIS: Two authors independently extracted outcome and quality data from each RCT. When appropriate, we undertook meta-analysis. MAIN RESULTS: We included 28 studies which examined a range of different antiemetics, used different doses and comparators, and reported a variety of outcomes. The quality and quantity of included studies limited the exploration of heterogeneity to narrative approaches only. The majority of quantitative data related to the complete control of acute vomiting (22 studies). Adverse events were reported in 24 studies and nausea outcomes in 10 studies. The addition of dexamethasone to 5-HT3 antagonists was assessed in two studies for complete control of vomiting (pooled relative risk (RR) 2.03; 95% CI 1.35 to 3.04). Three studies compared granisetron 20 mcg/kg with 40 mcg/kg for complete control of vomiting (pooled RR 0.93; 95% CI 0.80 to 1.07). No other pooled analyses were possible. Narrative synthesis suggests 5-HT3 antagonists are more effective than older antiemetic agents even when combined with a steroid. Cannabinoids are probably effective but produce frequent side effects. AUTHORS' CONCLUSIONS: Our overall knowledge of the most effective antiemetics to prevent chemotherapy-induced nausea and vomiting in childhood is incomplete. Future research should be undertaken in consultation with children, young people and families that have experienced chemotherapy and should make use of validated, age-appropriate measures. This review suggests that 5-HT3 antagonists with dexamethasone added are effective in patients who are to receive highly emetogenic chemotherapy although the risk-benefit profile of additional steroid remains uncertain.