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Aprepitant for the prevention of chemotherapy‐induced nausea and vomiting in adolescents

To the Editor: While aprepitant has been studied for definite indications and chemotherapy regimens in adults, evidence in adolescents is limited. Therefore, we read with interest the article by Gore et al. [1], the first randomized, double-blind, placebocontrolled trial of aprepitant in adolescents receiving emetogenic chemotherapy. Though this study represents the strongest evidence to date supporting aprepitant use in adolescents, several limitations were noted. Patients were randomized 2:1 to triple therapy or control regimen, yet four additional patients received open-label aprepitant after randomization. While this is problematic, these patients were not included in the efficacy analysis. Also, it was not stated which chemotherapy agents were used in the trial. This could potentially confound the results, especially if the number of patients receiving highly emetogenic chemotherapy in each group was not similar. However, since the most common diagnosis was bone sarcoma, some patients were likely treated with 5-day regimens of ifosfamide and etoposide, both of which have possible drug interactions with aprepitant, potentially increasing the risk of febrile neutropenia. Though no rationale is provided in the article for evaluating febrile neutropenia, it is concerning that a trend favoring an increased incidence in the aprepitant group was observed. Although the authors attribute this to the small study sample, this trend should be interpreted cautiously due to the high potential for drug interactions and lack of evidence supporting aprepitant use for more than 3 days with extended chemotherapy regimens. Finally, no formal statistical analysis was performed. All calculated confidence intervals were for estimation purposes and there was no adjustment for covariates. Therefore, it is difficult to estimate the true efficacy of aprepitant in clinical practice. While there are some limitations to this study, it is consistent with previous evidence supporting aprepitant use in adolescents. Two previous cases have been reported [2]. One case described the resolution of significant nausea, vomiting, and poor oral intake post aprepitant in a 16-year-old female with osteosarcoma (receiving cisplatin, doxorubicin, and methotrexate) [2]. Similarly, there is a report of a 17-year-old male with relapsed metastatic alveolar rhabdomyosarcoma (receiving irinotecan) who had complete resolution of ondansetron-resistant nausea and vomiting post aprepitant [2]. Additionally, a subgroup analysis of six adolescents in the Aprepitant Protocol 052 Study [3] showed that all three patients treated in the aprepitant group had no emesis or rescue therapy use compared to two of three patients treated with standard therapy [2]. This study combined with previous pediatric evidence [2,3] shows that aprepitant is not yet an up-front option for adolescents receiving emetogenic chemotherapy. These results should be interpreted cautiously because it is not clear from this small study whether the benefit of preventing nausea and vomiting is worth the risk of febrile neutropenia. However, this study does provide some guidance in treating adolescents receiving previously intolerable highly emetogenic chemotherapy with previous failure of all other anti-emetic options because it suggests that aprepitant, in combination with dexamethasone and ondansetron, may be effective and used safely in this population.