Dexamethasone dosing for prevention of acute chemotherapy‐induced vomiting in pediatric patients: A systematic review

Abstract

A systematic review was undertaken to describe dexamethasone doses studied for chemotherapy-induced vomiting (CIV) prophylaxis in pediatric patients and their effects on achieving complete acute CIV control. No dose-finding studies were identified. However, 16 studies assessing pediatric patients who received dexamethasone were included and classified according to the emetogenicity of chemotherapy administered. Eight different total daily dexamethasone doses were administered to patients on day 1 of highly emetogenic chemotherapy: three in conjunction with aprepitant/fosaprepitant plus a 5HT 3 antagonist and five in conjunction with a 5HT 3 antagonist. Five different total daily dexamethasone doses were administered in conjunction with a 5HT 3 antagonist to patients on day 1 of moderately emetogenic chemotherapy. Due to the heterogeneity of studies identified, meta-analysis was not possible. The optimal dexamethasone dose to control acute CIV and to minimize harms in pediatric patients remains uncertain. This is a key area for future research. K E Y W O R D S chemotherapy-induced nausea and vomiting, dexamethasone, pediatric oncology, supportive care 1 INTRODUCTION Chemotherapy-induced nausea and vomiting (CINV) are two of the most distressing side effects of chemotherapy. 1-3 They have a negative influence on quality of life, have been associated with decreased growth in children, and can lead to patients becoming nonadherent with oral chemotherapy and refusing to continue cancer treatment. 4-6 Dexamethasone has been included in pediatric CINV prophylaxis regimens for over three decades. 7 Current clinical practice guidelines (CPGs) for the prevention of acute CINV strongly recommend that pediatric patients receive dexamethasone in combination with Abbreviations: CINV, chemotherapy-induced nausea and vomiting; CIV, chemotherapy-induced vomiting; CPG, clinical practice guideline; HEC, highly emetogenic chemotherapy; MEC, moderately emetogenic chemotherapy aprepitant and a 5HT 3 antagonist during receipt of highly emetogenic chemotherapy (HEC) or in combination with a 5HT 3 antagonist during receipt of moderately emetogenic chemotherapy (MEC). 8-11 These CPGs acknowledge that there are circumstances when clinicians may wish to avoid the use of dexamethasone as an antiemetic and recommend alternatives. Such circumstances include brain tumors where corticosteroids may prevent chemotherapy distribution into the central nervous system 12 ; acute myelogenous leukemia where corticosteroids may further increase the already high risk of fungal infection 12 ; and use of chemotherapy where efficacy is compromised by concurrent corticosteroid use. 11 Nevertheless, inclusion of dexamethasone in pediatric CINV prophylaxis regimens and its appropriate dose are hotly debated among the pediatric oncology community. For example, two of 36 Children's Oncology Group member institutions responding to a survey in 2015 never administered dexamethasone for CIV

Overestimation of the effect of (fos)aprepitant on intravenous dexamethasone pharmacokinetics requires adaptation of the guidelines for children with chemotherapy-induced nausea and vomiting

“…In the other 34 institutions, 29 different dexamethasone dosing schedules were used for children receiving HEC [39]. A recent systematic review aimed to describe all different dexamethasone doses studied for the prevention of chemotherapy-induced vomiting (CIV) in pediatric patients and their effects on achieving complete acute CIV control [40]. However, due to the heterogeneity of the studies and the wide variety in dosing schedules, no optimal dexamethasone dose to control acute CIV was found.…”

“…However, due to the heterogeneity of the studies and the wide variety in dosing schedules, no optimal dexamethasone dose to control acute CIV was found. Dosing regimens varied from 6 to 27 mg/m 2 /day in patients receiving HEC and 0.6-24 mg/m 2 /day in patients receiving MEC [40].…”

Chemotherapy Induced Nausea and Vomiting in Children: A Literature Review and Recommendation for Antiemetic Prophylaxis in Resource Limited Countries

“…10 Dexamethasone is the corticosteroid that has most frequently been studied, and 5-HT3 antagonists with dexamethasone added are effective in patients receiving HEC. 13 Scaled pediatric dexamethasone doses, based on the recommended dose for adults (20 mg/day for HEC and 8 mg/day for MEC), suggested dexamethasone dosing for CINV prevention in the absent of NK-1 receptor antagonist as follows 14 HEC age ≤ 1 yr: 0. The most common adverse effects are steroid induced acne, increased appetite, insomnia and gastrointestinal symptoms.…”

Chemotherapy-induced nausea and vomiting in children – the missing evidence

“…24 Corticosteroid use is accompanied by common unpleasant adverse effects, especially after long-term use, such as weight gain, behavioural changes, gastrointestinal symptoms, insomnia, hyperglycaemia, and acne. 23,25 Osteonecrosis is a serious adverse effect that occurs in up to 40% of patients after long-term corticosteroid use, and the risk increases with higher doses and longterm exposure. 23 Dexamethasone exposure should therefore be limited to a minimal effective dose.…”