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

Abstract

Chemotherapy-induced nausea and vomiting (CINV) is a devastating adverse effect associated with treatment of childhood cancer that can lead to disruption of normal childhood activities and delay in important treatment with oral medicaments. Guidelines have been developed by several cancer associations helping clinicians to select proper antiemetic prophylaxis. [1][2][3][4] Generally, 5-hydroxytryptamine type 3 (5-HT 3 ) receptor antagonists, neurokinin 1 (NK 1 ) receptor antagonists, and dexamethasone are recommended to prevent CINV in children. The evidence directing these guidelines is limited by lack of available paediatric studies, and CINV control remains therefore often suboptimal for patients and a clinical challenge for healthcare professionals. However, emerging paediatric data are available in this increasingly popular research area, and newer antiemetic drugs, including olanzapine and lorazepam, may improve the CINV control.In this review, we provide information on the missing evidence in prevention and treatment of CINV in children, discuss barriers to use the available guidelines, and highlight areas for further research.

Background sensitivity to chemotherapy-induced nausea and vomiting and response to antiemetics in paediatric patients: a genetic association study

“…Chemotherapy regimens were classified as MEC (32%) or HEC (68%). Antiemetics were administered in accordance with a Danish guideline [13] (Supplemental digital content 1, http://links.lww.com/FPC/B415) and included 5-HT 3 receptor antagonists (ondansetron and palonosetron, n = 96), aprepitant ( n = 32), dexamethasone ( n = 32), and metopimazine ( n = 81) in different combinations according to the emetogenic potential of the administered chemotherapy. In total, 33% reached complete acute CINV control.…”

“…Also, development changes in expression of the proteins, different pathophysiology of the diseases, and differences in races of the included patients, their treatment regimens, and assessment of outcomes may explain why we were not able verify the findings. The principal neuroreceptors involved in the pathogenesis of CINV are 5-HT 3 , dopamine D2, and NK1 receptors [13], and data suggest that expression of these receptors undergoes development changes [24,25]. Results from pharmacogenetic studies of adults may therefore not be extrapolated to children.…”

Risk factors associated with nausea and vomiting in children with cancer receiving chemotherapy

“…Antiemetic prophylaxis was prescribed according to a Danish national guideline (Online Supplemental Table S1). 7…”

“…5 Consequently, nausea is often undertreated in children and ignored until vomiting occurs. 6 Antiemetic recommendations are based on four levels of emetic risk of the scheduled chemotherapy, [7][8][9][10] but even with appropriate antiemetic regimens before administering highly emetogenic chemotherapy (HEC), approximately 30% of patients suffer from vomiting, and nausea is even more frequent. [10][11][12] In adults, age under 50 years, female gender, low alcohol intake, anxiety for the treatment, and motion sickness or prior morning sickness during pregnancy are well-established risk factors for CINV, [13][14][15][16] and the CINV control can be improved if these patient factors are considered in the antiemetic recommendations.…”

“…5 Consequently, nausea is often undertreated in children and ignored until vomiting occurs. 6 Antiemetic recommendations are based on four levels of emetic risk of the scheduled chemotherapy, 7–10 but even with appropriate antiemetic regimens before administering highly emetogenic chemotherapy (HEC), approximately 30% of patients suffer from vomiting, and nausea is even more frequent. 10–12…”