<p>Efficacy, Safety And Feasibility Of Antiemetic Prophylaxis With Fosaprepitant, Granisetron And Dexamethasone In Pediatric Patients With Hemato-Oncological Malignancies</p>

Abstract

Background: Chemotherapy-induced nausea and vomiting (CINV) are a major burden for patients undergoing emetogenic chemotherapy. International guidelines recommend an antiemetic prophylaxis with corticosteroids, 5-HT 3 R-antagonists and NK 1 R-antagonists. The NK 1 R-antagonist fosaprepitant has shown favorable results in pediatric and adult patients. There is little pediatric experience with fosaprepitant. Methods: This non-interventional observation study analyzed 303 chemotherapy courses administered to 83 pediatric patients with a median age of 9 years (2-17 years), who received antiemetic prophylaxis either with fosaprepitant and granisetron with or without dexamethasone (fosaprepitant group/FG; n=41), or granisetron with or without dexamethasone (control group/CG; n=42), during moderately (CINV risk 30-90%) or highly (CINV risk>90%) emetogenic chemotherapy. The two groups' results were compared with respect to the safety and efficacy of the antiemetic prophylaxis during the acute (0-24hrs after chemotherapy), delayed (>24-120hrs after chemotherapy) and both CINV phases. Laboratory and clinical adverse events were compared between the two cohorts. Results: Adverse events were not significantly different in the two groups (p>0.05). Significantly fewer vomiting events occurred during antiemetic prophylaxis with fosaprepitant in the acute (23 vs 142 events; p<0.0001) and the delayed (71 vs 255 events; p<0.0001) CINV phase. In the control group, the percentage of chemotherapy courses with vomiting was significantly higher during the acute (24%/FG vs 45%/CG; p<0.0001) and delayed CINV phase (28%/FG vs 47%/CG; p=0.0004). Dimenhydrinate (rescue medication) was administered significantly more often in the CG, compared to the FG (114/FG vs 320/CG doses; p<0.0001). Likewise, in the control group, dimenhydrinate was administered in significantly more (p<0.0001) chemotherapy courses during the acute and delayed CINV phases (79 of 150; 52.7%), compared to the fosaprepitant group (45 of 153; 29.4%). Conclusion: Antiemetic prophylaxis with fosaprepitant and granisetron with or without dexamethasone was well tolerated, safe and effective in pediatric patients. However, larger prospective trials are needed to evaluate these findings.

<p>Antiemetic Prophylaxis with Fosaprepitant and 5-HT₃-Receptor Antagonists in Pediatric Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation</p>

“…20,21,27 In children receiving highly emetogenic chemotherapy, fosaprepitant was effective and well tolerated. 17,18,23,[28][29][30][31] In our previously performed analysis, it was demonstrated that the addition of single-dose IV fosaprepitant directly before starting the moderately or highly emetogenic conditioning chemotherapy prior to allogeneic HSCT, was safe and superior to the standard antiemetic prophylaxis regimen. 18 This is the first comparative analysis regarding the use of a fosaprepitant-based antiemetic prophylaxis regimen during highly emetogenic conditioning chemotherapy prior to autoHSCT in pediatric patients with hemato-oncological malignancies.…”

“…9 Despite the relatively small patient cohorts analyzed in this work, its results show the beneficial antiemetic effects of the fosaprepitant-based regimen and reaffirm the findings of previous analyses of fosaprepitant in children during moderately and highly emetogenic chemotherapy. 17,23,28,30,31 In view of the unsatisfactory control rates of vomiting despite the use of fosaprepitant in the patients undergoing autoHSCT, new or different antiemetic prophylaxis regimens are urgently needed to improve the supportive care of this rare patient cohort.…”

“…14,15 Prophylaxis regimens with 5-HT 3 -receptor antagonists with or without dexamethasone and fosaprepitant were safe and effective in pediatric and adult patients receiving highly emetogenic chemotherapy. [16][17][18][19][20][21][22][23] At present there is no study data available that analyzed the use of fosaprepitant in pediatric patients undergoing highly emetogenic conditioning chemotherapy prior to autoHSCT.…”

Summary of Literature on Pediatric Real-world Evidence and Effectiveness

“…Two reviewers agreed that 6 noninterventional publications met the criteria (Figure). A review of completed pragmatic trials for pediatrics in the ClinicalTrials.gov database from 2017 to 2019 did not identify any clinical trials that reported primarily relying on clinical RWD in the assessment of drug effectiveness. In examining common practices to control for bias in observational studies, we found that half of the 6 publications controlled for confounding by statistical analysis (Table), and none of the publications used propensity score matching.…”

Quality by Design Approach for Development and Characterization of Granisetron Hydrochloride-Loaded Orodispersible Films

“…Additionally, granisetron has a strong performance in terms of drug safety, allowing the application on children over 2 years old and patients aged 65 years or older. [4][5][6] Nevertheless, marketed pharmaceutical products still encounter challenges concerning patient compliance. Injections need to be administered by professional medical staff.…”