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