Discussion
This single-center, retrospective, cohort study showed that olanzapine, fosaprepitant, and a 5-HT3 receptor antagonist had similar control of CINV in pediatric patients receiving HEC compared to dexamethasone, fosaprepitant, and a 5-HT3 antagonist in the acute (53% v 63%, p=0.354) and delayed (80% v 73%, p=0.702) phases. The CR rates in this study are similar to other studies using three-drug antiemetic regimens in children. Bakhshi and colleagues demonstrated a CR in the acute phase of 48% v 12% when aprepitant was added to dexamethasone and ondansetron, and Kang and colleagues found CR rates of 51% v 26% in the delayed phase when aprepitant was added to ondasetron with or without dexamethasone. [6, 7]
Most studies continued olanzapine for 3-4 days after completion of chemotherapy; however, that was not the practice found in this study.[4, 8] To maximize olanzapine benefit, one could consider continuing olanzapine for up to 4 days after completion of chemotherapy. Additionally, when dexamethasone is not used, providers should consider using palonosetron instead of ondansetron as recommended in the COG CINV endorsed guidelines.[2] This recommendation is based on a meta-analysis demonstrating increased acute CINV control with palonosetron compared to other 5-HT3 antagonists in the absence of dexamethasone. [9]
This study was limited by its retrospective design and incidence of nausea and vomiting and other toxicities relied on documentation in the electronic medical record. As a result, mild adverse events may have been unreported. In this study, only one patient required a dose modification due to over-sedation. The incidence of over-sedation in other studies range from 35-40%.[4, 8] The limited sedation experienced in this study may be due to the lower starting dose of olanzapine use compared to other studies (0.07 mg/kg v 0.14 mg/kg).[4, 8] In this study, the standard dose of 0.05 mg/kg/dose was chosen to allow for an additional as needed dose without exceeding the maximum daily dose of olanzapine that has been studied in the pediatric population.
In conclusion, olanzapine appears to be a safe and effective alternative to dexamethasone as part of a three-drug prophylaxis regimen for both acute and delayed CINV. Future studies are warranted to determine the benefit of olanzapine in combination with palonosetron and fosaprepitant when dexamethasone must be avoided.
Table 1. Baseline characteristics