Antiemetic Prophylaxis with Granisetron and Fosaprepitant during Moderate and High Emetogenic Chemotherapy in Pediatric Patients

Background

Pediatric patients that undergo chemotherapy and hematopoietic stem cell transplantation regularly experience chemotherapy-induced nausea and vomiting (CINV), which represents a major impairment of the patients' quality of life. Antiemetic prophylaxis is thus an important factor in cancer therapy management. Risk for CINV is defined by >30-60% in moderate and by >60% in high emetogenic therapy. International guidelines recommend antiemetic prophylaxis with a combination of corticosteroids, 5-HT₃R-antagonists (5-hydroxytryptamine-3 receptor) and NK₁R-antagonists (neurokinin-1 receptor). Especially the water-soluble NK₁R-antagonist fosaprepitant has shown favorable results in adult patients when used in a combination prophylaxis with the 5-HT₃R-antagonist granisetron. This is the first comparative analysis to assess the efficacy and safety of a combination of intravenous fosaprepitant, granisetron and dexamethasone versus a standard prophylaxis regimen with granisetron and dexamethasone alone in 86 pediatric patients.

Results

In this retrospective single-center chart analysis, a total of 86 pediatric patients with a median age of 7 years (2-17 years) were enrolled between 2015 and 2017. The patients received either antiemetic prophylaxis with intravenous infusion (<30 minutes) of granisetron (2x20 µg per kg bodyweight and day (maximum 3 mg), fosaprepitant 3.5 - 4 mg per kg bodyweight (maximum 150 mg) and dexamethasone 0.1 mg per kg bodyweight (maximum 4 mg) (fosaprepitant group; FG; n=45) or granisetron and dexamethasone alone (control group; CG; n=41) for the prevention of CINV in 308 courses of moderate or high emetogenic chemotherapy. Patients experiencing vomiting or receiving antiemetic medication within 48 hours before the start of antiemetic prophylaxis were excluded from this analysis. Antiemetic efficacy of the two prophylaxis regimens was comparatively analyzed with respect to vomiting frequency, percentages of patients experiencing vomiting, and additional therapeutic medication with dimenhydrinate in the acute (<24h) and delayed (24-100h) CINV phases. Safety was assessed comparing drug-related clinical (exanthema, sweating, and gastrointestinal symptoms) and laboratory (relevant changes of liver and kidney parameters, electrolytes) side effects.

Both prophylaxis regimens were similarly safe and not significantly different (p>0.05) with respect to clinical or laboratory drug-related adverse events. Discontinuation of the antiemetic medication was not indicated for any of the patients of the CG or FG. Percentages of patients experiencing vomiting was significantly lower in the FG, both in the acute CINV phase (p<0.01) and in the delayed CINV phase (p<0.001) when compared to the CG. Likewise, significantly fewer vomiting events were registered during antiemetic prophylaxis with additional fosaprepitant in the acute (p<0.001) and the delayed CINV phase (p<0.001). This effect was also seen in significantly less administered dimenhydrinate doses (p<0.001) and a significantly lower percentage of patients needing additional medication with dimenhydrinate (p<0.001).

Conclusion

In conclusion, additional single-dose fosaprepitant in combination with the standard antiemetic regimen with granisetron and dexamethasone proved to be safe and effective as antiemetic prophylaxis in pediatric patients receiving moderate or high emetogenic therapy. Observed drug-related side effects were similar in both study groups. Efficacy of a triple-prophylaxis with the NK₁R-antagonists fosaprepitant in combination with the 5-HT₃R-antagonist granisetron and the corticosteroid dexamethasone was significantly superior when compared to a prophylaxis regimen with granisetron plus dexamethasone alone.

Acknowledgments

This study was supported by the Stefan-Morsch-Stiftung, Birkenfeld, Germany.