Flank, J., Robinson, P.D., Holdsworth, M., Phillips, R., Portwine, C., Gibson, P., . . . Dupuis, L.L. (2016). Guideline for the treatment of breakthrough and the prevention of refractory chemotherapy-induced nausea and vomiting in children with cancer. Pediatric Blood and Cancer, 63, 1144–1151.

DOI Link

Purpose & Patient Population

PURPOSE: To optimize the control of breakthrough and refractory chemotherapy-induced nausea and vomiting (CINV) in children
 
TYPES OF PATIENTS ADDRESSED: Pediatric patients with cancer aged 1 month to 18 years receiving chemotherapy

Type of Resource/Evidence-Based Process

RESOURCE TYPE: Evidence-based guideline

PROCESS OF DEVELOPMENT: Systematic reviews were conducted for breakthrough and refractory CINV, including evidence from adults and children, and systematic reviews were conducted to evaluate the evidence regarding the safety of various medications in children. The GRADES system was used to categorize evidence. External and stakeholder reviews were done.
 
DATABASES USED: MEDLINE, EMBASE, CENTRAL, and PsycINFO
 
INCLUSION CRITERIA: All research designs, reported proportion with complete control (CC) in patients with refractory symptoms, described response to the first dose of breakthrough treatment for studies with treatment versus prevention interventions
 
EXCLUSION CRITERIA: Case studies and case series

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Pediatrics

Results Provided in the Reference

Five thousand nine hundred ninety-three citations were retrieved, and 59 studies were included—13 for breakthrough CINV and 46 for refractory CINV. Very limited evidence in children existed, of which much was weak, as well as evidence regarding the safety and optimal dosages of breakthrough medications, such as metoclopramide and methotrimeprazine, for children.

Guidelines & Recommendations

Breakthrough: Upgrade prophylaxis regimen to that recommended for chemotherapy of the next highest level of emetogenic risk. Add olanzapine to guideline-consistent prophylaxis with highly emetogenic chemotherapy (HEC). Add methotrimeprazine or metoclopramide if olanzapine cannot be used, given the weighing of risks and benefits.
 
Refractory: Upgrade regimen to that recommended for next highest level of emetogenic risk. Use 5-HT3 palonosetron or granisetron rather than ondansetron. If aprepitant was not previously used, adding aprepitant should be considered. If these do not resolve the problem, add methotrimeprazine or metoclopromide.

Limitations

The review and guideline development process were conducted very well, but limitations include the lack of sufficient evidence for interventions in pediatric patients. Even those recommendations that were presented as strong recommendations were noted to be based on weak evidence.

Nursing Implications

This guideline provides specific recommendations for alterations in CINV prophylaxis to address breakthrough and refractory CINV in children. It has also exposed research gaps in the areas of efficacy of prophylaxis escalation, optimal dose, efficacy and safety of olanzapine, methotrimeprazine and metoclopramide, optimal palonosetron dose with multiple day chemotherapy, and the extent and clinical significance of interactions between aprepitant and chemotherapy. Safety of metoclopramide in children related to side effects of extrapyramidal symptoms is also questioned.